Graduate School of Medicine Kyoto University 2011

Transcription

Kyoto University
2011
Graduate School of Medicine Kyoto University 2011
Graduate School of Medicine
The Goal of the Graduate School of Medicine and
Faculty of Medicine of Kyoto University
– To develop a new realm of medical science and to create
innovative medical treatment.
Nagahiro Minato
Dean of the Graduate School of Medicine and
Faculty of Medicine
Kyoto University
The Kyoto University Graduate School of Medicine offers four programs in which to major: Medicine, Medical Science,
Public Health and Human Health Science. Each program can be taken to the masters and doctoral level (except for
Medicine, which offers a doctorate only). The Graduate School is one of the largest in Japan, with an enrolment of 893
postgraduate students (as of October 2010). Our research domains cover the entire spectrum in medicine, healthcare and
human health and welfare, including basic medicine, clinical medicine, social medicine and medical technology.
Our Graduate School has a mission: to educate international leaders who would engage in the drive to generate
knowledge in the domains of medicine and healthcare and to contribute to the improvement of human health and welfare
by continually deploying this knowledge to the world around us. Truly, we are living in an age of universalization and
globalization. To accomplish our mission in this present-day context, we need an interdisciplinary approach. Extremely
important is the discovery and development of new domains, through borderless interaction of enthusiastic students with
diverse expertise and academic background, not only students who have basic training in the fields of medicine but also
students who hail from non-medical disciplines.
In 2005, the Kyoto University Graduate School of Medicine became the first in Japan to initiate a new graduate training
system. This Graduate Course of Integrated Research Training consists of some ten research areas (courses) relatively
wide in universal scope. Students joining the Graduate School will choose one or more of these courses according
to their own interests, regardless of the particular degree course or areas they are studying and irrespective of the
boundaries of basic, clinical or social medicine. Regular research presentations and discussions are held, directing
students into research activities that involve a broad perspective. Academic staffs also participate in one of the training
courses according to their interests and expertise as individual researchers, regardless of the academic programs and
specialist areas to which they appertain. The Course is principally run by students on a voluntary basis. Not only does
it bring a broad perspective to research activities but it also has proved exceedingly useful in information exchange
and promotion of new joint research projects within the Graduate School. The graduate teaching undertaken by the
Graduate School consists of two main pillars: training through this Graduate Course of Integrated Research training and
the conventional one-to-one research tutoring in specific research areas. We are confident that this framework is fully
beneficial to the development of wide-ranging knowledge and research capacity of students. The Graduate School is a
Global Center of Excellence (COE) designated by the Ministry of Education, Culture, Sports Science and Technology of
the Japanese Government. The chief purpose of the COE is the pioneering of new research domains and globalization of
research by means of collaboration and integration of many leading-edge research domains. As part of COE activities,
we are sending our students overseas as well as receiving students from overseas, and we are establishing the practice of
students giving seminars and research presentations in English.
I believe that the most important task of the Graduate School of Medicine is to train global leaders who can become the
engines for progress in medicine and healthcare through their wide scientific knowledge and excellent research capacity
and who can communicate with the world with originality. You all know well that we have a track record of producing
world-class experts and brilliant research results. We hope that students who come to the Graduate School will join in
our vigorous stream of research and success and be the very pioneers of the academia of the future.
Graduate School of Medicine Kyoto University | 1
INDEX
Admission Policy···········································································
4
Dermatology ················································································· 66
Curriculum Policy ··········································································
8
Pediatrics ······················································································ 67
Diploma Policy ·············································································· 12
Radiation Oncology and Image-Applied Therapy ························· 68
Research Field List ······································································· 14
Diagnostic Imaging and Nuclear Medicine ··································· 69
Clinical Laboratory Medicine ························································ 70
Gastrointestinal Surgery ······························································· 71
Medicine (Doctoral Program)
Medical Science
(Master / Doctoral Program)
Hepatopancreatobiliary Surgery and Transplantation··················· 72
Breast Surgery ············································································· 73
Anesthesia ···················································································· 74
Gynecology and Obstetrics ·························································· 75
Basic Medicine (Core Departments)
Urology ························································································· 76
Biological Sciences······································································· 28
Cardiovascular Surgery ································································ 77
Anatomy and Developmental Biology ··········································· 29
Thoracic Surgery ·········································································· 78
Anatomy and Cell Biology ···························································· 30
Plastic and Reconstructive Surgery·············································· 79
Physiology and Biophysics ··························································· 31
Ophthalmology and Visual Sciences ············································ 80
Pharmacology ·············································································· 32
Otolaryngology-Head and Neck Surgery······································ 81
Pathology and Tumor Biology ······················································· 33
Orthopaedic and Musculoskeletal Surgery··································· 82
Pathology and Biology of Diseases ·············································· 34
Oral and Maxillofacial Surgery······················································ 83
Diagnostic Pathology ···································································· 35
Clinical Molecular Biology····························································· 84
Microbiology ················································································· 36
Neurology ····················································································· 85
Immunology and Cell Biology ······················································· 37
Neurosurgery················································································ 86
Forensic Medicine and Molecular Pathology ································ 38
Psychiatry ····················································································· 87
Medical Chemistry ········································································ 39
Transfusion Medicine and Cell Therapy ········································ 88
Cell Biology··················································································· 40
Diagnostic Pathology ···································································· 89
Molecular Oncology ······································································ 41
Medical Informatics······································································· 90
Molecular Genetics ······································································· 42
Pharmacy ····················································································· 91
Radiation Genetics ······································································· 43
Experimental Therapeutics ··························································· 92
Morphological Brain Science ························································ 44
Clinical Trial Design and Management ········································· 93
Integrative Brain Science ······························································ 45
Clinical Innovative Medicine ························································· 94
Physiology and Neurobiology ······················································· 46
Brain Pathophysiology / Functional Brain Imaging
(Human Brain Research Center) ·················································· 95
Cell Pharmacology ······································································· 47
Public Health ················································································ 48
Organ Preservation Technology
(Contributed Chairs) ····································································· 96
Laboratory Animal Science
(Institute of Laboratory Animals)··················································· 49
Multidisciplinary Cancer Treatment
(Contributed Chairs)
Congenital Anomaly Research Center ········································· 50
Respiratory Care and Sleep Control Medicine
Human Disease Genomics
(Center for Genomic Medicine) ···················································· 51
Genome Informatics
Medical Education
(Center for Medical Education) ····················································· 53
Translational Clinical Oncology
Translational Research Center
Ghrelin Research Project ····························································· 99
Immunology and Genomic Medicine
Lactosome Project ········································································ 100
Statistical Genetics
Radiation Biology Center
Clinical Medicine (Core Departments)
Hematology and Oncology ··························································· 56
Medicine and Clinical Science ······················································ 57
Cardiovascular Medicine ······························································ 58
Gastroenterology and Hepatology ················································ 59
Respiratory Medicine ···································································· 60
Department of Radiation System Biology
(Laboratory of Genome Maintenance) ········································· 101
Department of Mutagenesis
(Division of Chromatin Regulatory Network) ································ 102
Department of Late Effect Studies
(Laboratory of DNA Damage Signaling) ······································ 103
Department of Genome Dynamics
(Laboratory of Genome Dynamics) ············································· 104
Rheumatology and Clinical Immunology ······································ 61
Institute for Chemical Research
Geriatric Medicine ········································································ 62
Chemical Biology ·········································································· 105
Diabetes and Clinical Nutrition ····················································· 63
Primary Care and Emergency Medicine······································· 64
Institute for Frontier Medical Sciences
Nephrology ··················································································· 65
Molecular and Cellular Biology ····················································· 106
2 | Graduate School of Medicine
Kyoto University
Ultrastructural Research ······························································· 107
Pharmacoepidemiology ································································ 143
Experimental Pathology································································ 108
Immunobiology and Hematology ·················································· 109
Cellular Differentiation ·································································· 110
Development and Differentiation ·················································· 111
Growth Regulation ········································································ 112
Immunology ·················································································· 113
Tissue Regeneration ···································································· 114
Organ Reconstruction··································································· 115
Bioartificial Organs ······································································· 116
Nano Bioprocesses ······································································ 117
Medical Simulation Engineering ··················································· 118
Healthcare Economics and Quality Management ························ 145
Medical Ethics / Medical Genetics ················································ 146
Health Informatics········································································· 147
Medical Communication ······························································· 148
Management of Technology and Intellectual Property·················· 149
Health and Environmental Sciences············································· 150
Health Promotion and Human Behavior ······································· 151
Preventive Services ······································································ 152
Global Health and Socio-epidemiology ········································ 153
Public Health and International Health ········································· 154
Institute for Virus Research
Gene Analysis ·············································································· 119
Cell Regulation ············································································· 120
Ecology with Emphasis on the Environment
(Center for Southeast Asian Studies) ··········································· 155
Field Medicine
(Center for Southeast Asian Studies) ··········································· 156
Laboratory of Human Tumor Viruses ············································ 121
Laboratory of Biological Protection ··············································· 122
Laboratory of Infection and Prevention ········································· 123
Human Health Science
Laboratory of Growth Regulation·················································· 124
Pathogenesis ················································································ 125
Viral Infections ·············································································· 126
Viral Pathogenicity ········································································ 127
Nursing Science
Environmental Health Nursing ······················································ 157
Human Body Defense & Patho-physiology Nursing Science········ 158
Research Reactor Institute
Nursing Science for Lifestyle-Related Diseases ··························· 159
Radiation Biology·········································································· 128
Psychiatric Nursing ······································································· 160
Particle Radiation Oncology ························································· 129
Critical Care Nursing ···································································· 161
Child Health and Development Nursing········································ 162
Center for Southeast Asian Studies
Midwifery and Women's Health ···················································· 163
Pathogenic Microbiology······························································· 130
Female Life-Cycle Nursing
Field Medicine ·············································································· 131
Preventive Nursing ······································································· 164
Center for iPS Cell Research and Application (CiRA)
Public Health Nursing
Home Healthcare Nursing ···························································· 165
Reprogramming Regulation Field ················································· 132
Differentiation Induction Field ······················································· 133
Laboratory Science
Disease modeling with patient-derived iPS cells ························· 134
Basic Laboratory Science ····························································· 166
Kyoto University Health Service
Preventive Services ······································································ 135
Institute for Integrated Cell-Material Sciences (iCeMS)
Developmental Biology ································································· 136
Affiliate Graduate School
Medical Embryology
(RIKEN Center for Developmental Biology) ·································· 137
Reproductive Biotechnology
Developmental Biology
(Osaka Bioscience Institute) ························································· 139
Application Biology and Regenerative Medicine
Public Health
Innovational Laboratory Medicine················································· 167
Applied Laboratory Science ························································· 168
Medical Devices for Diagnoses ···················································· 169
Innovative Medical Imaging Technology ······································· 170
Medical Imaging System Sciences ··············································· 171
Rehabilitation Sciences
Motor Function Analysis ······························································· 172
Development and Rehabilitation of Motor Funcition ····················· 173
Clinical Cognitive Neuroscience ··················································· 174
Brain Function and Rehabilitation················································· 175
Fusion Unit for Near Future Human Health Sciences
Innovation Unit for Near Future System and Technology ············· 176
Contact Information /
Human Health Science ················································· 177
(Professional Degree Program / Doctoral Program)
Access Guide ····························································· 179
Biostatistics··················································································· 141
Epidemiology and Healthcare Research ······································ 142
Admission Policy
Doctoral (PhD) Program in Medicine
It is the solemn duty of medical researchers to unravel the mysteries of the human body, elucidate the mechanisms
that cause illness, and to apply this knowledge to the prevention and treatment of disease. Today we are witnessing
unprecedented momentum in the compartmentalization of medical fields, diversification and internationalization.
Therefore the burden of expectations placed upon medical researchers is now greater than ever. Modern medical
researchers must not only possess unsurpassed knowledge in their respective fields of expertise, but broadening
their horizons to the diverse array of academic sub-specialties is implied in their occupational mandate.
Additionally, to become a truly well-rounded medical researcher in the era of globalization, one must be able
to establish collaboration with other laboratories, and make an invaluable contribution to the international
community. This is our vision for the researchers we hope to develop in the Graduate School of Medicine, PhD
(Medicine) program.
Based on this vision, what started off as 6 independent research fields within the Graduate School of Medicine
were consolidated in 2006 to help promote interdisciplinary interaction. In addition to traditional classroom
instruction and training seminars, we introduced the Graduate School Training Course which bridges the gap
between Clinical, Basic and Social Medicine. The PhD program offers this and other programs that place PhD
candidates at their core. By nurturing the autonomy of PhD candidates, we hope to develop researchers who will
lead medical research towards unprecedented progress in the 21st century. Individuals with demonstrated superior
academic achievements actively seeking to put their knowledge and technical skills to use in the field of medical
research are strongly encouraged to apply.
Master of Science (MS) Program in Medical Science
The Master of Science (MS) program in Medical Science was established for the noble purpose of developing
highly qualified researchers in the field of medical science that meet the highest of professional and ethical
standards. Consequently, candidates enrolled under the MS (Medical Science) degree program with no background
in the natural sciences will be required to successfully negotiate a rigorous training regimen structured largely
upon challenging classroom instruction in the fields of basic medical science, and complete intensive training
in medical science research. As with all other programs offered under the Graduate School of Medicine, degree
candidates will be exposed to a highly competitive, yet equally fulfilling academic environment that constantly
redefines their cognitive potential.
The MS program at the Graduate School of Medicine boasts an open stance on admissions and actively seeks
highly motivated individuals representing diverse academic backgrounds to conduct pioneering research in
medical research at one of the world’s most prominent research institutions.
Kyoto University
Doctoral (PhD) Program in Medical Science
Our rapidly evolving understanding of the life sciences has resulted in swift changes in the healthcare and medical
environments. With that, research and educational initiatives within the medical community has also become
increasingly more advanced and complex. Until now, the traditional medical education system revolved around
the development of medical practitioners; however, with remarkable advances in our understanding of the life
sciences, it is imperative that medical professionals effectively make use of this information for transition into
novel therapeutic techniques.
We are now witnessing drastic changes in the way physicians diagnose patients. Today more than ever, physicians
are relying heavily upon advanced medical devices for diagnostic assistance. Research encompassing these
medical devices and diagnostic techniques are actively being conducted on a daily basis, and carry with them the
hopes and dreams of a quickly aging population.
As society’s pinnacle of research and education, developing aggressive researchers to venture beyond the
framework of traditional medical education and research is the solemn mission assigned to all universities.
In the PhD (Medical Science) program, we answer society’s call by bringing together individuals who have
demonstrated superior academic achievement in the natural sciences and engineering, and training them on the
many diverse perspectives of medicine to become the world’s leading researchers/educators in medical science.
Professional Degree Program in School of Public Health
This program is structured specifically for students who wish to seek a future in public health, medicine or
welfare, as an educator or technical specialist. Students enrolled in this program will receive training to acquire
knowledge, technical skills and professionalism in the field of Public Health. Upon completion of training,
graduates will be able to detect, evaluate, analyze and problem-solve the many public health issues that plague
the “health of our society” today. Because the program provides an assortment of academic fields to specialize
in—everything from the natural sciences to human social science—our policy on admissions are very open, and
qualified individuals from all walks of life are encouraged to apply. We welcome highly motivated applicants
from various academic disciplines who display a strong conviction to be an advanced professional or educator/
researcher in health, medicine, and welfare in Japan and abroad.
Management of Technology and Intellectual Property Course (Est. 2004)
Japan is quickly becoming oriented to the international race for intellectual property rights and is active in
the application of patents in the medical field. Therefore, Japan is in need of advanced professionals who can
secure and manage the intellectual property rights of advanced medical research initiatives when they bear fruit.
Applicants eager to pursue a future in intellectual asset management are encouraged to apply.
Clinical Researcher Training Course (Master of Clinical Research, MCR; Est. 2005)
The MCR is an intensive 1-year program designed specifically for medical doctors and dentists. Until now, the
majority of medical research conducted in Japan revolved primarily around the life sciences; however, there is a
growing understanding now on the importance of human and population based clinical studies. The MCR is the
first program of its kind to be offered in Japan, and is devoted to training medical professionals who will assume
future careers as physician-scientists. Applications are openly welcome from individuals who have nurtured an
interest in conducting clinical research based on their own clinical experiences.
Genetic Counseling and Clinical Research Unit (Est. 2006)
In actuality, this program stems from two distinct courses: the Genetic Counseling Course and the Clinical
Research Unit. Our mission is to train genetic counselors and clinical research coordinators who are intellectually
capable, are well-versed, and can lead future initiatives in frontier medicine. Using the skills honed in these
programs, our graduates will serve as an interface between novel medical techniques and those who will directly
benefit from these techniques (patients, families, and research subjects). Individuals with a strong pioneering spirit
and eager to conduct frontier clinical research are encouraged to apply.
Doctoral (PhD) Program in School of Public Health
This course aims at developing researchers who will focus on the detection, evaluation, analysis, and resolution
of the countless health issues that compromise “the health of society”. Students who complete this course are
expected to engage in advanced education/research initiatives in public health, medicine, and welfare not only
in Japan, but in other countries as well. This course is truly multidisciplinary, covering an assortment of fields
from the natural sciences to the human social sciences. Therefore, we welcome applicants carious academic
backgrounds who are eager to perform research on public health issues.
Kyoto University
Master of Science (MS) Program in School of Human Health
Science
While we have witnessed much progress over the years in our understanding of Medicine and its application
to various avenues of treatment, further evolution is imperative in meeting the medical demands of the future.
The Graduate School of Medicine at Kyoto University has long-since been a forerunner in pushing forward the
advancement of medical technology. To ensure that generations to come will have open access to high quality
public health, medical care, and welfare in Japan, we proposed the creation of a new scientific field called Human
Health Sciences. The MS program at the School of Human Health Science logically defines the concept of “health”
it strives to pursue, and provides extensive training and education in order to secure the demand for highly
qualified future healthcare professionals. Based on these principles, we provide healthcare providers with superior
clinical and communication skills who can provide superior medical care that meets the demands of patients.
Additionally, we combine basic and clinical medicine, along with other academic disciplines and intellectual
assets at Kyoto University to develop future educators and researchers. Individuals with a passion for supporting
the healthcare efforts of the future are encouraged to apply.
Doctoral (PhD) Program in School of Human Health Science
Throughout its proud heritage, Kyoto University has always assumed a central role in the prevention and treatment
of disease. The PhD program at the School of Human Health Science was established for the humble purpose
of nurturing professionals who can promote the concept of genuine health, establish a theoretical foundation
for research in the field of Human Health Sciences, and apply this theoretical foundation into actual practice
to overcome disease. In order to maintain its leadership role in the field of medicine/medical science, Kyoto
University requires PhD candidates to explore beyond the reaches of their respective areas of expertise, and
actively seek knowledge in a wide array of academic fields that will enable them to assume leadership roles in
multi-disciplinary environments. To this end, the Merger Unit for Future Human Health Sciences—consisting of
an orchestra of researchers representing the fields of medicine, engineering, pharmacology, the natural sciences,
social studies, and the humanities—was established in order to promote novel theories and practices for physical
and psychological diagnosis, patient treatment, and the sustenance of daily health. Given our future perspective,
it is our mission to develop experts who will become leaders in the ever-evolving field of Human Health Science.
Therefore, it is our hope to not only attract individuals with a background in Medicine and the Medical Sciences,
but also those representing the public and private sectors. Upon completion of studies at the School of Human
Health Science, graduates will return to the industrial, public and academic domains as invaluable assets. Highly
qualified and motivated individuals are actively sought for this program.
Curriculum Policy
Curriculum in Medicine
In the PhD program, students will select their own respective posts of assignment from an assortment of renowned
departments and laboratories at the Graduate School of Medicine, Kyoto University. It is there that prospective
PhD candidates will acquire the fundamental skills and knowledge required to plan, conduct and complete a
respectable project in basic and clinical medical research. PhD candidates will also be assigned to at least one of
the Graduate School Training Courses, which bridges the gap between Clinical, Basic and Social Medicine.
In the Graduate School Training Course, degree candidates will hone their knowledge and sense of ethics as future
researchers, and further benefit from periodic interactive seminars with professors where ideas can be freely
exchanged. Through this active exchange, students will gain a broader perspective on the concept of medical
research, and learn to nurture vital skills in establishing collaboration, which will enable them to erect new
avenues of research.
Using this approach based on comprehensive training in the fundamental principles of medical science and
emphasizing the importance of teamwork, it is our sincerest hope that the graduates of this program will
transcend the boundaries that inhibit collaboration amongst researchers, and become the world’s leading medical
researchers/educators.
Curriculum in Medical Science
Under the Master of Science (MS) program, students with no background in medicine receive instruction in
the basic medical sciences and training in research methodologies to become broad-minded and extraordinary
researchers in the challenging field of medicine. In just 2 years, students with no background in the biological
sciences will acquire a working and fundamental understanding of the natural sciences via the comprehensive
coursework offered under this program. The initial 4-month period in the MS program will be devoted to intensive
classroom instruction in the essential sciences and laboratory training. After this phase, students will select one
laboratory—from an assortment of more than 110—to conduct research throughout the remainder of their MS
candidacies, where their knowledge and skills acquired in other academic disciplines will be utilized to the fullest
extent.
On the other end of the spectrum, students enrolled in the PhD program will be directly assigned to their
laboratory-of-choice upon entrance, where they will receive continuous training on how to plan and complete a
medical research project on their own. To supplement their training, PhD candidates will also be assigned to one
of the Graduate School Training Courses, which bridges the gap between Basic, Clinical and Social Medicine.
In the Graduate School Training Course, PhD candidates will broaden their horizons via exposure to students
and staff representing other fields of medical expetise. Through these interactions, PhD candidates will acquire a
Kyoto University
broader perspective and learn first-hand the importance of establishing collaboration on the sometimes arduous
road to discovering uncharted territories in the field of medicine.
Based on this approach combining comprehensive instruction in the fundamental medical sciences and
emphasizing the importance of collaboration, the PhD program aims to develop highly competent researchers
that will transcend the boundaries of compartmentalization and become the world’s leading medical researchers/
educators.
Curriculum in School of Public Health
The professional degree program offered under the School of Public Health is designed to develop multifaceted
professionals who will pursue a career in public health, medicine or welfare. Upon completion of the program,
graduates will be able to detect, evaluate, analyze and problem-solve the many public health issues that
threaten the health of society’s key component—the individual. To develop fully capable professionals, we
offer a curriculum based on comprehensive instruction in the fundamental subjects, training to apply acquired
knowledge to real-world situations, and hands-on training. Instruction in the “fundamental subjects” implies the
core principles (epidemiology, medical statistics, environmental science, administration/management, and social
science) of science that all experts hold as common ground in the field of Public Health. For graduates with no
background in medicine, we provide extensive training in subjects covering basic and clinical medical subjects.
In addition to providing instruction on the fundamental principles of medicine, we offer “applied learning” which
comes in the form of diverse electives and includes everything from courses in the frontier medical sciences
to human social sciences. In terms of “practical training,” every student is assigned a topic for a subjective
study. Under this segment of training, students will plan a project, evaluate the ethical considerations, conduct
experiments and present their findings in the same fashion as professional researchers.
To augment the traditional, systematic coursework and curricula, the School of Public Health established three
special training courses to develop professionals in highly technical fields.
Management of Technology and Intellectual Property Course
This course was established for the sole purpose of developing professionals who can manage the end product of
frontier medical research, as intellectual assets. Students electing this course will acquire specialized knowledge in
intellectual property rights and technical management practices. In order to develop highly qualified professionals,
the Management of Technology and Intellectual Course provides practical training in patenting, establishing an
invention, screening for existing patents, making invoices, business planning and contract writing, in addition to
standard classroom instruction in biology, medicine, technical management and law (intellectual property law,
patent law).
Clinical Researcher Training Course (Master of Clinical Research, MCR)
Designed specifically for medical doctors and dentists, the Clinical Researcher Training Course is a one-year
intensive course to develop highly qualified clinically-oriented epidemiological researchers. Upon graduation,
students enrolled under this program will be highly proficient in erecting a concept for a clinical research
project based on their own personal experiences, and establish relevant research protocols, manage and conduct
experiments, analyze data, interpret the results and prepare a manuscript detailing the contents of the project.
Genetic Counseling and Clinical Research Unit
This is a combined program composed by the Genetic Counseling and Clinical Research Units. In either unit,
the mission is to train genetic counselors and clinical research coordinators who are intellectually capable, wellversed, and can lead future initiatives in frontier medicine. Graduates will serve as an interface between novel
medical/therapeutic techniques, and their beneficiaries (patients, families, and research subjects). Through a
combination of traditional classroom instruction and practical training, graduates of the Genetic Counseling
and Clinical Research Units will have acquired the knowledge and skills required to successfully negotiate the
Certified Genetic Counselor examination and Clinical Coordinator certification examination (administered by the
Japan Clinical Pharmacology Association), respectively.
The doctoral (PhD) degree program offered under the School of Public Health is designed to provide training in
all essential subject areas and technical skills, and strengthens the mental fortitude of degree candidates who seek
a future in Public Health. Upon completion of the program, graduates will be able to detect, evaluate, analyze and
problem-solve the many public health issues that threaten the health of society’s key component—the individual.
The expectations that society has of Public Health professionals are high. Therefore, the PhD curriculum is content
in offering advanced education and training initiatives in public health that will make its graduates competitive
on the global arena. PhD candidates who did not complete the professional degree program offered at the Kyoto
University School of Public Health, are obligated to complete coursework in the core subject areas (epidemiology,
medical statistics, environmental science, administration/management, and social science). PhD candidates with
no background in medicine will also be required to complete courses in basic medicine and clinical medicine in
order to ensure the high standard of quality that graduates of Kyoto University are synonymous for.
Curriculum in School of Human Health Science
To ensure that generations to come will have open access to high quality public health, medical care, and welfare
in Japan, we proposed the creation of a new scientific field called Human Health Sciences.
The MS program at the School of Human Health Science aims to push forward the momentum of advanced
frontier medicine, and seeks to secure a solid foundation of healthcare, welfare and social insurance for future
generations. Additionally, the School of Human Health Science logically defines the concept of “health” it strives
to pursue for future generations, and provides extensive training and education in order to fulfill this goal. The
MS program offers courses in Nursing Science, Laboratory Analysis and Rehabilitation Science. In either course,
MS candidates will be expected to meet the highest standards of professionalism and demonstrate a high degree of
Kyoto University
knowledge in Human Health Science. Through diverse curricula, the MS course hopes to develop researchers who
can bridge the gap between basic and clinical medicine, and can establish cooperative projects with laboratories
representing various academic disciplines in the hopes of making unprecedented progress in the unexplored
reaches of human health science.
The PhD program at the School of Human Health Science was established for the humble purpose of nurturing
professionals who can promote the concept of genuine health, establish a theoretical foundation for research in
the field of Human Health Sciences, and apply this theoretical foundation into actual practice to overcome the
constant threat of disease. In order to assume a central role in the field of human health sciences, a PhD candidate
must not only be proficient in his/her domain of expertise, but must also possess administrative and managerial
skills in a variety of disciplines. To this end, the Merger Unit for Future Human Health Sciences—consisting of
an orchestra of researchers representing the fields of medicine, engineering, pharmacology, the natural sciences,
social studies, and the humanities—was established in order to promote novel theories and practices for physical
and psychological diagnosis, patient treatment, and the sustenance of daily health. PhD candidates will be
provided with ample training and education that will enable them to become future leaders in the constantly
evolving field of Human Health Science.
Diploma Policy
Degrees in Medicine
Under the PhD program, students will receive 4+ years of intensive post-graduate training. During this time,
degree candidates must complete at least 24 units in subject courses, at least 6 units in Graduate School Training
Courses, and have a manuscript published as the first author in a peer-reviewed international journal of prominent
standing. Lastly, PhD candidates must successfully negotiate an oral thesis defense prior to being conferred upon
the PhD degree.
Degrees may be awarded upon completion of the 3rd (or midway through the 4th) year of PhD studies under
special circumstances in which a candidate’s absolute independence as a researcher has been clearly demonstrated.
To qualify under this special provision, a candidate must demonstrate his/her ability to erect a concept for a
medical research project, and be able to plan, implement and compile the results of the project in a manuscript of
impeccable quality. Furthermore, the manuscript must be published in a prominent journal of exceptional standing
within the global scientific community for consideration under this provision. After these requisites have been
met, a candidate will next be administered a written PhD aptitude battery. Final conference of degrees will be
determined following the candidate’s satisfactory completion of the aptitude battery.
Degrees in Medical Science
Under the Master of Science (MS) program, students must receive 2+ years of training, and will be required to
complete at least 30 units in subject courses (in addition to completing subjective studies). Additionally, a master’s
thesis detailing the candidate’s research topic must be submitted for review, and will be followed by an oral thesis
defense prior to being conferred upon the MS degree.
Candidates under the PhD program must be enrolled and receive training in research for 3+ years, and are required
to complete at least 11 units of graduate coursework (7 in major subjects, and 4 in minor subjects). Additionally,
PhD candidates must have a manuscript published (as the first author) in a peer-reviewed international scientific
journal of prominent standing and are required to undergo an oral thesis defense on the candidate’s published work
prior to being awarded the PhD degree.
Degrees in School of Public Health
Candidates applying for a professional degree under the Public Health program must receive 2+ years of training,
and complete at least 30 units in subject courses (in addition to completing subjective studies). Those enrolled
under the “special course” must meet additional requirements regarding compulsory courses. The topic of
the subjective study shall be determined by—and executed at—the laboratory in which the candidate resides.
Subjective studies will mold a solid concept of research in degree candidates via intensive first-hand training in
establishing research protocols, data acquisition and analysis, and interpreting the results of a study. In addition to
Kyoto University
completing the required coursework and subjective study, candidates must pass an oral thesis defense in order to
be conferred upon the professional degree in Public Health.
Candidates under the Public Health PhD program must be enrolled and receive training for a period of 3+
years, in which time candidates will be responsible for completing required coursework. The minimum amount
of coursework units required for graduation depends upon a candidate’s academic background. Holders of
professional degrees awarded in Public Health by Kyoto University need only complete 6 units of coursework.
For graduates of institutions other than Kyoto University: those awarded degrees in subjects related to Medicine
must complete 13 or more units, and those awarded degrees in non-medical subject areas must complete 19 or
more units. Additionally, PhD candidates must have a manuscript published (as the first author) in a peer-reviewed
international scientific journal of prominent standing and are required to undergo an oral thesis defense on the
candidate’s published work prior to being awarded the PhD degree.
Degrees in School of Human Health Science
Candidates under the Human Health Science MS program must be enrolled for a period of 2+ years and complete
a minimum of 30 units of coursework in subjects consistent with the educational philosophy of the School of
Human Health Science. Additionally, candidates must receive ongoing research training, submit a Master’s thesis
and pass an oral thesis defense. Required coursework falls into one of four major subject classifications: Major
required subjects, general required subjects, electives and special research assignments. A candidate can obtain
coursework units by attending lectures, seminars, labs, clinical training sessions and field work.
CNS program candidates must be enrolled for a period of 2+ years and complete a minimum of 32 units of
coursework in (cancer CNS) subjects consistent with the educational philosophy of the School of Human Health
Science. Additionally, candidates must submit a Master’s thesis and pass an examination administered by the
School of Human Health Science.
A panel of judges will comprehensively evaluate a Master’s thesis based on criteria such as novelty, academic
significance, creativity and practical applicability. Similarly, in addition to being evaluated on research progress,
ethical considerations, and ability to logically present the outcome of a study, degree candidates will be tested in
order to confirm that they possess ample knowledge in the field of study.
Candidates accepted under the Human Health Science PhD program must be enrolled for a period of 3+ years and
complete a minimum of 16 units of coursework (special lectures, special seminars, merger unit courses and special
research assignments) in subjects consistent with the educational philosophy of the School of Human Health
Science. Additionally, candidates must receive ongoing research training, submit a PhD thesis and pass an oral
thesis defense.
A panel of judges will comprehensively evaluate a PhD thesis based on criteria such as novelty, academic
significance, creativity and practical applicability. Similarly, in addition to being evaluated on research progress,
a candidate must hold to the highest standards of ethics, and must demonstrate the ability to logically present the
outcome of a study. Furthermore, degree candidates will be tested in order to confirm that they possess ample
knowledge in subjects encompassing the field of study. Only those who successfully meet all of the defined
requirements will be awarded the PhD degree.
Research Field List
Medicine
(Doctoral Program)
/ Medical Science
(Master /Doctoral Program)
Basic Medicine (Core Departments)
Research Field
Professor
Biological Sciences
Dai WATANABE
Anatomy and Developmental
Biology
Anatomy and Cell Biology
Masatoshi HAGIWARA
Pharmacology
Makoto Mark TAKETO
Pathology and Tumor Biology
Pathology and Biology of
Diseases
Michiyuki MATSUDA
Diagnostic Pathology
Forensic Medicine and Molecular
Pathology
Molecular Genetics
Study of information processing in the brain
●
Study of sensori-motor integration
●
Study of morphogenesis and differentiation
●
Decipherment of splicing code
●
Development of new drugs to cure RNA diseases
●
Study of origin, properties, and regulation of the germ cell lineage
●
Molecular mechanisms of epigenetic reprogramming in vivo and in vitro
●
Study of in vitro reconstruction of germ cell development
●
Molecular mechanisms of self renewal of stem cells
●
Molecular mechanism of cardiac muscle cell function
●
Molecular control mechanism of ion channel function
●
Blood circulation control system
●
Molecular genetic study of cancers of digestive organs using knockout mice
●
Study of cancer microenvironment in invasion and metastasis
●
Search for cancer therapeutics based on above studies
●
Study of molecular mechanism of individual aging
●
Molecular biology of neuronetwork formation
●
Study of molecules controlling formation, maintenance, and differentiation of reproductive
cells
●
Study of molecular mechanism of axial formation in mammalian embryo
●
Study of human pathology, cancer control genes, and carcinogenesis mechanism
●
Live cell imaging of growth factor signal transduction network
●
Study of cancer cell invasion and metastasis with live cell imaging techniques
●
Systems analysis of oncogene signaling network
●
Pathological diagnostics (surgical pathology) and cytodiagnosis
●
Clinicopathological study using surgical pathological materials
●
Application of immunohistochemistry to pathology
●
Computerization of pathological diagnostic tasks
●
Molecular mechanism of intracellular parasitism of bacteria (Listeria and Mycobacteria)
●
Study of Immune response of the host against bacterial infection
●
Mechanism of virulence factor-dependent cytokine response
●
Biochemical study on cholesterol-dependent cytolysins
●
Development and regulation of immune cells and tissues
●
Small G protein signaling in normal development of lymphocytes and leukemia genesis
●
Mechanisms of anti-tumor immunity and its application
●
Regulation of hematopoiesis and myeloproliferative disorders
●
Forensic genetics ecompassing human DNA polymorphisms
●
Study of instability in tandem repeat sequences
●
Retroviral and pathological assessment of blastic B-cell lymphoma
●
Molecular mechanism of cell death
●
Engulfment of dead cells, and its abnormality
●
Assymmetrical distribution of phospholipids in plasma membrane
●
X-ray crystallography on membrane proteins
●
Structure and mechanism of G-protein coupled receptors
●
Structure and Mechanism of membrane transporters
●
Molecular mechanisms of carcinogenesis
●
Roles of RECK, a membrane anchored MMP regulator, in development and diseases
●
Genes and chemicals suppressing malignant phenotypes of tumor cells
●
Study of development and control of stem cell system
●
Reproductive engineering using spermatozoon stem cells
Masao MITSUYAMA
Immunology and Cell Biology
Molecular Oncology
Study of functional brain development
●
Hironori HAGA
Microbiology
Cell Biology
●
Mitinori SAITOU
Physiology and Biophysics
Medical Chemistry
Area of Research
Nagahiro MINATO
Keiji TAMAKI
Shigekazu NAGATA
So IWATA
Makoto NODA
Takashi SHINOHARA
Kyoto University
Research Field
Radiation Genetics
Morphological Brain Science
Integrative Brain Science
Physiology and Neurobiology
Cell Pharmacology
Public Health
(Institute of Laboratory Animals)
Congenital Anomaly Research
Center
(Center for Genomic Medicine)
Professor
Shunichi TAKEDA
Takeshi KANEKO
Kenji KAWANO
Area of Research
●
Hereditary factors related to carcinogenesis
●
Mechanism of acquisition of resistance to radio-/chemotherapy of cancers
●
Gene therapy using homologous DNA recombination
●
Mechanism of maintenance and inheritance of chromosomal DNA
●
Screening of environmental carcinogenic chemicals
●
Experimental morphological and theoretical study of cerebral cortex nerve circuit
●
Electrophysiological and morphological study of local circuit of the central nervous system
●
Experimental morphology of neuronal connection of the central nervous system
●
Experimental morphology of circuit formation of the central nervous system
●
Experimental morphology of neuroactive substances and receptors
●
Study of information processing system of the brain
●
Study of neuronal mechanism of visual control of movement
●
Study of higher brain function
●
Functional study of synapses of the central nervous system
●
Feature extraction and processing of auditory information
●
Study of role of prostaglandin receptors in chronic inflammation and diseases
●
Study of emotional behavior and its abnormality under stress
●
Study of cellular function of small G protein Rho and its role in the body
●
Study of role of cytoskeletal dynamics in neuronal plasticity
●
Study of health policy
●
Study of international health
●
Study of health promotion and health education
●
Development and genetic analysis of disease model animals
●
Development of genetically modified rat strains
●
Study of rat strain characteristics
●
Malformation
●
Molecular cell biological study of mechanism of abnormal development
●
Hereditary epidemiological study of causes of malformation
●
Reproductive and developmental toxicology
●
Identification of genetic factors related to human multifactorial diseases
●
Genetic epidemiology of community-based prospective genome cohorts
●
Development of database for the management of genomic studies
●
Comparative genomic study on gene regulation
●
Bioinformatics analysis of splice regulation
●
High-throughput gene expression data analysis on cancer cells
●
Coordination of undergraduate and postgraduate medical education
●
Coordination of faculty development and staff development for medical education
●
Coordination of interprofessional education in the medical field
●
Study of learning sciences for medical education
●
Study of patient safety
●
Study of resuscitation science and prehospital care
●
Study of communication for medical interview
●
Study on molecular mechanisms for immunoglobulin diversification
●
Study on genomic instability related to immunoglobulin gene alteration
●
Study on immune-regulatory mechanism of costimulatory molecules
●
Development of methods in phenotye mapping
●
Study of genetic polymorohpisms and heterogeneity
Harunori OHMORI
Shuh NARUMIYA
Toshitaka NAKAHARA
Tadao SERIKAWA
Keiji TAMAKI
Fumihiko MATSUDA
Genome Informatics
Medical Education
(Center for Medical Education)
Immunology and Genomic
Medicine
Tasuku HONJO
Ryo YAMADA
Research Field List
Research Field
Professor
Hematology and Oncology
Akifumi TAKAORI
Medicine and Clinical Science
Cardiovascular Medicine
Gastroenterology and
Hepatology
Respiratory Medicine
Rheumatology and Clinical
Immunology
Kazuwa NAKAO
Takeshi KIMURA
Tsutomu CHIBA
●
Basic and clinical studies of tumors of hematopoietic organs
●
Study of pathophysiology of anemia
●
Study of pathophysiology of iron metabolism
●
Study of pathology and control of infectious diseases
●
Basic and clinical studies of cellular immunotherapy
●
Study of differentiation and function of blood cells
●
Basic study of gene therapy
●
Study of causes, prevention, and therapy of lifestyle-related disorders
●
Basic and clinical studies of metabolic syndrome
●
Basic and clinical studies of diabetes mellitus
●
Basic and clinical studies of hypertension
●
Basic and clinical studies of obesity
●
Basic and clinical studies of endocrine disorders
●
Basic and clinical studies of bone metabolic disorders
●
Basic and clinical studies of cardiovascular, renal, and cerebrovascular complications in
lifestyle-related disorders
●
Basic and clinical studies of cardiovascular endocrinology and metabolism
●
Regenerative medicine of lifestyle-relted disorders
●
Development study of diagnostic and therapeutic methods for ischemic heart diseases
●
Basic and clinical studies of prevention of cardiovascular diseases (Mainly, gene
diagnosis)
●
Basic and clinical studies of arrhythmia
●
Basic and clinical studies of development and progression of arteriosclerotic diseases
●
Basic and clinical studies of prevention and therapy of aneurysm
●
Development study of gene therapy and cell therapy for cardiovascular diseases
●
Basic and clinical studies of pathology of heart failure
●
Basic and clinical studies of cardiac sudden death
●
Basic and clinical studies of cause, diagnosis, and therapy of cardiomyopathy
●
Basic and clinical studies of hypertension
●
Study of pathological progression of renal disorders
●
Clinical study of interventional cardiology
●
Molecular biological study of cancers of digestive organs (including liver cancer)
●
Immunological, molecular biological, and clinical studies of viral hepatitis and autoimmune
diseases of the liver, biliary tract, and pancreas
●
Immunological and molecular biological study of inflammatory intestinal diseases
●
Molecular biological study of differentiation and regeneration of the intestinal tract and
liver
●
Clinical study of endoscopic therapy
●
Basic and clinical studies of liver circulation
●
Imaging diagnosis and medical therapy of liver cancer
●
Pathogenesis, pathophysiology, diagnosis and treatment of airway diseases (COPD,
asthma, and chronic cough)
●
Multi-disciplinary investigation, diagnosis and management (including non-invasive
ventilation) of respiratory failure and sleep apnea syndrome
●
Clinical studies, diagnosis and management of lung cancer
●
Basic and clinical studies and management of interstitial lung diseases
●
Bacteriology, pathophysiology and treatment of respiratory infections
●
Basic and clinical studies of rheumatic and connective tissue diseases
●
Basic and cliniccal studies of allergic diseases
●
Molecular pathophysiology of autoimmunity
●
Autoantibody production mechanism
●
Clinical and pathogenic significance of autoantibodies
●
Basic and clinical studies of development mechanism of aging-related arteriosclerosis
●
Study of comprehensive geriatric assessment
●
Study of osteoporosis
●
Basic and clinical studies of dementia and memory
●
Basic and clinical studies of ageing
Michiaki MISHIMA
Tsuneyo MIMORI
Geriatric Medicine
Area of Research
Kyoto University
Research Field
Diabetes and Clinical Nutrition
Primary Care and Emergency
Medicine
Professor
Pediatrics
Radiation Oncology and ImageApplied Therapy
Diagnostic Imaging and Nuclear
Medicine
Clinical Laboratory Medicine
Gastrointestinal Surgery
●
Study of insulin secretion
●
Study of glucose, lipid, and protein homeostasis
●
Study of metabolism in beta-cell and liver
●
Development of beta-cell imaging
●
Pathophysiological and genetic studies of diabetes mellitus
●
Study of diabetic complications
●
Study of secretion and action of incretin
●
Clinical study of diabetes mellitus and nutritional disorders
●
Study of primary care medicine
●
Study of emergency medicine
●
Basic and clinical studies of shock
●
Basic and clinical studies of sepsis
●
Study of optimal apheresis therapy for various diseases
●
Clinical study of indication of hemodialysis and peritoneal dialysis for ESRD
●
Study of the mechanism of onset and progression of diabetic nephropathy
●
Study of factors affecting the generation and development of the kidney
●
Study of the metabolism of drugs in the kidney
●
Study of immune and allergic skin diseases
●
Study of inflammatory skin diseases
●
Study of ultraviolet light biology
●
Cell biological study of skin diseases
●
Molecular biological study of skin diseases
●
Study of skin regeneration medicine
●
Study of development and regeneration of organs and tissues
●
Study of congenital metabolic abnormality
●
Study of allergic diseases in children
●
Study of immunological diseases in children
●
Study of pediatric neurology and muscular disorders
●
Study of pediatric heart diseases
●
Study of pediatric blood disorders and tumors
●
Study of neonatal diseases
●
Systematization from diagnosis to therapy of cancer
●
Development of fourth dimensional radiotherapy
●
Development of image-guided radiation therapy
●
Development of molecular target drugs with radiosensitizing effects
●
Molecular biology and molecular imaging of hypoxic cancer cells
●
Development of new diagnostic imaging methods with MRI, CT, PET, US, RI, etc for all
human body regions and organs
●
Application of imaging modalities to image-guided therapeutics
●
Computer-aided diagnosis and related image processing
●
Development of new imaging methods and modalities in cooperation with school of
engineering and corporations
●
Basic research on the medical image
●
Study of laboratory diagnostics of infectious diseases
●
Study of infection control and therapeutics
●
Study of electrocardiographic diagnostics
●
Study of neurophysiological test diagnostics
●
Molecular biological analysis of gastrointestinal cancers
●
Study of gastrointestinal physiology
●
Study of surgical anatomy
●
Development of surgical instruments
●
Clinical study of gastrointestinal cancers
Nobuya INAGAKI
Kaoru KOIKE
Nephrology
Dermatology
Area of Research
Yoshiki MIYACHI
Toshio HEIKE
Masahiro HIRAOKA
Kaori TOGASHI
Satoshi ICHIYAMA
Yoshiharu SAKAI
Research Field List
Research Field
Professor
Hepatopancreatobiliary Surgery
and Transplantation
Breast Surgery
Anesthesia
Gynecology and Obstetrics
Urology
Cardiovascular Surgery
Thoracic Surgery
Plastic and Reconstructive
Surgery
Area of Research
●
• Study of pancreatic cancer and its precursors
●
• Study of nutrition and ERAS (enhanced recovery after surgery)
●
• Study of genesis/regeneration of the pancreas
●
• Study of angiogenesis and hepato-biliary-pancreatic disease
●
• Study of pancreatic islet transplantation
●
• Study of development of engineered liver grafts
●
• Study of regeneration of the liver
●
• Study of organ preservation and chimera for liver transplantation
●
• Study of immune tolerance after liver transplantation
●
• Study of hepato-biliary oncology
●
• Study of hepato-biliary fibrosis
●
• Study of pediatric surgery
●
Breast cancer stem cell and adipose stem cell study
●
Development of a novel and less invasive therapy
●
Biomarker study for optimizing systemic and local therapy
●
Clinical development and application of bio-optical devices
●
Study of treatment algorithms for breast cancer patients
●
Study of surgical stress and biological reaction
●
Study of circulatory physiology and pharmacology related to surgery and anesthesia
●
Study of neurophysiology and pharmacology related to pain and pain relief
●
Molecular biological study of anesthesia and related drugs
●
Study of platelet function related to surgery and anesthesia
●
Study of hypoxic responses in anesthesia and intensive care
●
Study of reproductive and developmental medicine
●
Study of infertility therapy
●
Study of malignant ovarian tumor
●
Study of uterine tumor
●
Study of endometoriosis
●
Study of perinatal medicine
●
Study of fetal medicine
●
Study of reproductive endocrinology
●
Study of reproductive immunology
●
Study of urogenital tumors
●
Study of male reproductive system
●
Study of renal replacement therapy
●
Study of bladder pathophysiology
●
Study on regeneration of urogenital tissues
●
Study of heart transplantation and assist circulation
●
Study of myocardial regeneration
●
Study of surigical ventricular restoration
●
Study of therapeutic angiogenesis for limb ischemia
●
Study of new myocardial protection
●
Development of novel devices for endovascular surgery
●
Thoracic surgery
●
Lung cancer, mediastinal tumor, and chest wall tumor
●
Lung transplantation
●
Study of regeneration medicine of respiratory organs
●
Gene therapy for lung cancer
●
Study of regeneration of skin and subcutaneous tissues
●
Study of wound healing, scar and keloid
●
Study of biomaterials
●
Study of regeneration of cartilage, bone, and nerve
●
Study of skin microcirculation
●
Study of cleft lip and palate, and other congenital deformities
Shinji UEMOTO
Masakazu TOI
Kazuhiko FUKUDA
Ikuo KONISHI
Osamu OGAWA
Ryuzo SAKATA
Hiroshi DATE
Shigehiko SUZUKI
Kyoto University
Research Field
Ophthalmology and Visual
Sciences
Otolaryngology-Head and Neck
Surgery
Orthopaedic and Musculoskeletal
Surgery
Oral and Maxillofacial Surgery
Clinical Molecular Biology
Neurology
Neurosurgery
Psychiatry
Professor
Area of Research
●
Study of age-related macular degeneration (AMD)
●
Study of diabetic retinopathy
●
Study of glaucoma
●
Study of retinal microcirculation
●
Study of regeneration of retina and optic nerve
●
Study of ocular fundus imaging
●
Study of adaptive optics scanning laser ophthalmoscopy (AO-SLO)
●
Study of genome association in AMD and high myopia/degenerative myopia
●
Study of regeneration of inner ear hair cells
●
Study of speech cognition and expression mechanism
●
Study of regulation of body equilibrium
●
Study of ventilation physiology of middle ear
●
Molecular biological study of malignant tumors of the head and neck
●
Study of laryngeal pathophysiology
●
Study of regeneration of aerodygestive tract
●
Study of artificial bone and joint materialsStudy of bone and cartilage development
●
Study of bone and cartilage metabolism
●
Study of bone and soft tissue tumors
●
Study of spinal surgery
●
Study of osteoarthritis and rheumatoid arthritis
●
Study of hand surgery and peripheral nerve regeneration
●
Study of regenerative medicine of musculoskeletal system
●
Study of hard tissue regeneration
●
Molecular biological study of tooth regeneration
●
Study of artificial tooth root and periodontal tissue regeneration
●
Study of orthognathic surgery of jaw deformity
●
Study of craniomaxillofacial development
●
Molecular biological study of jaw and oral cavity disorders
●
Mastication and higher brain function
●
Study of kinetics of oral microbial flora
●
Molecular biological study of reproductive cell differentiation
●
Molecular mechanism of liver cancer development and development of therapeutic
method
●
Study of stress response
●
Study of development mechanism and therapy of extrapyramidal tract disorders including
Parkinson disease
●
Study of pathogenesis and therapy of neurodegenerative disorders including amyotrophic
lateral sclerosis
●
Study of development mechanism and therapy of Alzheimer disease and related dimentia
●
Study of diagnosis and therapy of intractable partial epilepsy
●
Study of cerebral vascular disorder and cerebral circulation/metabolism
●
Electrophysiological and pathological study of muscular and peripheral nervous diseases
●
Study of cerebrovascular disorders
●
Study of brain tumors
●
Study of functional brain neurosurgery
●
Study of neural regeneration and neuroplasticity
●
Study of intravascular surgery
●
Study of vascular metabolic function
●
Electrophysiological study of the central nervous system
●
Gene therapy for cerebrovascular disorder and brain tumors
●
Viral therapy for brain tumors
●
Study of pituitary gland generation
●
Neuroimaging
●
Psychopathology
●
Neuropsychology
●
Child and adolescent psychiatry
●
Forensic psychiatry
Nagahisa YOSHIMURA
Juichi ITO
Takashi NAKAMURA
Kazuhisa BESSHO
Jun FUJITA
Ryosuke TAKAHASHI
Susumu MIYAMOTO
Toshiya MURAI
Research Field List
Research Field
Professor
Transfusion Medicine and
Cell Therapy
Taira MAEKAWA
Area of Research
●
Development of novel medical test methods of anti-HLA antobody for supporting cell
therapy and organ transplantation
●
Development of cell processing technology for advanced cellular therapy and regenerative
medicine
●
Study for controlling acute GVHD of hematopoietic stem cell transplantation using
meschenchymal stem cells
●
Development of cancer molecular targeting therapy
●
Study of transcriptional regulations for normal and malignant hematopoietic stem cells
●
Research for cell lineage of immature myeloid cells
●
Pathological diagnostics (surgical pathology) and cytodiagnosis
●
Clinicopathological study using surgical pathological materials
●
Application of immunohistochemistry to pathology
●
Computerization of pathological diagnostic tasks
●
Electronic Health Record System and Personal Health Record System
●
Hospital information system and clinical imaging system
●
Virtual Reality (VR) system for medical use
●
Natural language processing technology for medical knowledge
●
Basics and clinics of pharmacokinetics, pharmacological effects, and toxicity of drugs
●
Study of molecular mechanism and clinical application of drug transporters
●
Study of variation of pharmacokinetics and pharmacological effects in pathological states
and individual dosing design
●
Elucidation of drug transporters, genetic polymorphism of metabolic enzymes, and
individual variation and application to tailor-made medical care
●
Exploratory study of development of novel medical careDevelopment of medical care
based on analysis of genomic structure and gene expression
●
Methodology for clinical development of novel medical products
●
Design, data management, statistical analysis, and interpretation for clinical studies
●
Researches on statistical analysis methods
●
Development of holistic medical system for advanced therapeutics and diagnosis
●
Study of cooperative medical care by various job types for practice of novel therapeutics
and diagnosis
●
Study of comprehensive support system for the patients undergoing novel therapies and
diagnosis
●
Study of development of exploring therapy for atherosclerotic disorders
●
Study of psychological and somatic care for the patients with intractable diseases
including cancer
●
Non-invasive study of movement control by the central nervous system and its disorders
in humans
●
Non-invasive study of cognitive and memorizing functions and its disorders in humans
●
Clinicophysiological study of neurological disorders
●
Study of higher function of human brain by imaging of brain function
●
Analysis of neurotransmitters by imaging of brain function
●
Development of new noninvasive brain imaging devices for noninvasive brain
●
Researches on preservation of organs, tissues, and cells
●
Development of new preservation technologies
●
Study of causes, prevention, and therapy of respiratory failure
●
Basic and clinical studies of sleep medicine
●
Basic and clinical studies of sleep disordered breathing
●
Clinical studies of respiratory care
●
Basic and clinical studies of sustained and intermittent hypoxemia
●
Clinical study of cancer chemotherapy
●
Clinical study of supportive care medicine in cancer chemotherapy
●
Pharmacogenetic study of cancer chemotherapy
●
Molecular pathology of human cancer
Hironori HAGA
Medical Informatics
Hiroyuki YOSHIHARA
Pharmacy
Experimental Therapeutics
Akira SHIMIZU
Clinical Trial Design and
Management
Clinical Innovative Medicine
Masayuki YOKODE
Brain Pathophysiology /
Functional Brain Imaging
(Human Brain Research Center)
Hidenao FUKUYAMA
Multidisciplinary Cancer
Treatment
Respiratory Care and
Sleep Control Medicine
Kazuo CHIN
(Hwa Boo JIN)
Kyoto University
Research Field
Professor
Area of Research
Ghrelin Research Project
Takashi AKAMIZU
●
Exploratory study for new drug development of Ghrelin
●
Exploratory study for molecular imaging probe on cancer
Lactosome Project
Shunsaku KIMURA
●
Exploratory study for nanocarrier on drug delivery system
●
Exploratory study on diagnostic and therapeutic agents
Social Medicine
Research Field
Professor
Area of Research
●
Measurement and analysis of quality of care and outcomes
●
Quantitative evaluation of diagnostic measures
●
Study on clinical reasoning
●
Researches on new drug approval and regulatory systems
●
Reseaches on clinical trials
●
Drug safety researches including pharmacoepidemiology and pharmacoeconomics
●
●
Hybrid peptide therapiy researches focusing cancer and inflammatory diseases
●
Policy and economics of health care
●
Management of healthcare organizations
●
Healthcare reform in policy and system
●
Quality, safety, efficiency and equity of health care and its improvement
●
Costing, pricing and performance measurement in health care
●
Study of ethical examination
●
Study of medical care for heredity
●
Study of medical care policy
●
Genetic epidemiology of lifestyle disorders
●
Risk evaluation of Persistent Organic Pollutants
●
Genetic epidemiology of preventable multifactorial diseases
●
Industrial toxicology
Masahiro KIHARA
●
Socio-epidemiological study of prevention of HIV infection
Research Field
Professor
Area of Research
Department of Radiation System
Biology (Laboratory of Genome
Maintenance)
Tomohiro
MATSUMOTO
●
Radiation response of cell cycle
●
Genomic stability and carcinogenesis
●
Study of mechanism of muatagenesis
●
Study of DNA radiation injury repair system
●
Study of biological rhythm control by light
●
Mechanisms of genetic instability in cancer
●
Signal transduction mechanisms in DNA damage response
●
Molecular pathogenesis of Fanconia anemia and related medical conditions
●
DNA recombination and cell cycle control
●
Chromosomal instability-associated human hereditary diseases and genomic dynamics
●
Intracellular network of various DNA repair proteins
Epidemiology and
Healthcare Research
Pharmacoepidemiology
Healthcare Economics and
Quality Management
Medical Ethics
Health and Environmental
Sciences
Global Health and
Socio-epidemiology
Shunichi FUKUHARA
Koji KAWAKAMI
Yuichi IMANAKA
Shinji KOSUGI
Akio KOIZUMI
(Division of Chromatin
Regulatory Network)
Department of Late Effect
Studies (Laboratory of DNA
Damage Signaling)
Minoru TAKATA
Department of Genome
Dynamics (Laboratory of
Genome Dynamics)
Kenshi KOMATSU
Research Field
Professor
Chemical Biology
Motonari UESUGI
Area of Research
●
Discovery and design of small molecule tools for cell biology and cell therapy
●
Cell biology empowered by small molecules
●
Small molecule-based bioimaging
Research Field List
Research Field
Professor
Area of Research
●
Study of quality control mechanism in mammalian cells
●
Cell biological study of molecular chaperones
●
Study of general transcription regulatory system
●
Study of basics and application of RNA aptamer
●
Cell biological study of molecular basis of introduction and maintenance of immune
tolerance
●
Study of cause and development mechanism of autoimmune diseases
●
Study of tumor immunity induction mechanism and transplantation immune tolerance
mechanism
●
Study of cause and development mechanism of rheumatoid arthritis
●
Action mechanism of chemokines in development and immune response
●
Molecular control system of development of blood and immune system cells
●
Molecular basis of microenvironments in organs supporting stem and progenitor cells
●
Organ-specific molecular mechanism of angiogenesis
●
Study of molecular mechanism of osteogenesis and chondrogenesis
●
Study of anti-angiogenic barriers in mesenchymal tissues
●
Study of development and differentiation of germ lineage cells
●
Developmental engineering research using mouse ES cell lines
●
Derivation and basic research of human ES cell lines
●
Application of ES/iPS cell lines for disease models and drug discovery research
●
Intercellular interaciton in morphogenesis
●
Study of cell proliferation and differentiation control mechanism in development and
regeneration
●
Study of tissue construction mechanism
●
Study of thymus, thymic lymphoma and T cell differentiation
●
Study of T cell receptor gene rearrangement
●
Study of proliferation and differentiation of mesenchymal cells
●
Study of transformation of mesenchymal cells
●
Regenerative medicine of mesenchymal tissues
●
Development of regeneration medicine for metabolic disorders
●
Development of pancreatic islet regeneration therapy for diabetes
●
Induciton of stem cell differentiation to pancreatic islet, nerve, liver, and cardiac muscle
●
Development of regeneration medicine using encapsulated cells and/or tissues
●
Study of tissue engineering
●
Study of diagnosis and therapeutics by medical engineering
●
Development study of reconstructive surgery and artificial organs
●
Developing single-molecule imaging/manipulation technology, applicable to living cells
●
Elucidating signal transduction mechanisms in/on the plasma membrane, including
GPCRs, receptor-type tyrosine kinases, raft-associated receptors, with a special attention
paid to nano-meso membrane domains and multiple-molecular complexes
●
Elucidating neuronal activity-dependent formation and modulation mechanisms of
neuronal circuits
●
Elucidating the interactions between the plasma membrane and the cytoskeleton
●
Study of simulation medical engineering
●
Study of biomechanics
●
Study of medical materials
●
Study of medical system engineering
Molecular and Cellular Biology
Ultrastructural Research
Experimental Pathology
Shimon SAKAGUCHI
Immunobiology and Hematology
Cellular Differentiation
Takashi NAGASAWA
Yuji HIRAKI
Development and Differentiation
Norio NAKATSUJI
Atsuko SEHARAFUJISAWA
Growth Regulation
Immunology
Tissue Regeneration
Junya TOGUCHIDA
Organ Reconstruction
Bioartificial Organs
Nano Bioprocesses
Akihiro KUSUMI
Medical Simulation Engineering
Kyoto University
Research Field
Gene Analysis
Cell Regulation
Laboratory of Human Tumor
Viruses
Laboratory of Biological
Protection
Professor
Yoshinori AKIYAMA
Masahiko SUGITA
Keizo TOMONAGA
Pathogenesis
Viral Infections
Viral Pathogenicity
●
Study of protein dynamics in bacterial cell surface
●
Biological study of human immunodeficiency virus
●
Study of carcinogenesis inhibitors and promoters at the molecular level
●
Biological study of human papillomavirus
●
Molecular biology of Wnt signal transmission pathway
●
A paradigm for lipid-specific immune responses in disease
●
Lipid biology of microbes and cancer cells
●
Vaccine development against human tuberculosis and AIDS
●
Molecular mechanism of bornavirus pathogenesis and replication
●
Molecular biological analysis of influenza virus infection
●
Development of RNA virus vectors
●
Molecular biological study of hepatitis C virus
●
Molecular biological study of proliferation control of hepatitis C virus-infected cells
●
Epigenetic control of lymphocyte antigen receptor genes
●
Role of cytokine receptor in differentiation and maintenance of lymphocytes
●
Control of cytokine receptor gene expression during immune development and response
●
Imaging and in vivo function of immune microenvironment
●
Molecular biology of immune allergic diseases
●
Molecular biology of thioredoxin family
●
Study of stress signals and redox regulation
●
Molecular mechanism of carcinogenesis and hyperlipidemia
●
Molecular mechanism of differentiation, development, and regeneration of neurons
●
Gene expression control system of the nervous system
●
Study of biological clocks controlling development
●
Molecular biological study of retrovirus replication mechanism
●
Elucidative study of pathogenicity of HIV
●
Basic study for gene therapy
Koichi IKUTA
Laboratory of Infection and
Prevention
Laboratory of Growth Regulation
Area of Research
Ryoichiro KAGEYAMA
Yoshio KOYANAGI
Masao MATSUOKA
●
Molecular mechanism of human T cell leukemia virus associated pathogenesis
●
Development of therapeutic strategy to HTLV-1 associated diseases
●
Development of new anti-HIV-1 drugs, and mechanism of resistant viruses
●
Molecular biological study of pathogenicity and leukemogenicty of AIDS and ATL viruses
●
Molecular immunological and molecular genetic study of origin, evolution, and mutation of
AIDS and ATL viruses
●
Immunological study of infection and disease development mechanisms of AIDS and ATL
viruses and basic sutdy for vaccine development
Tatsuhiko IGARASHI
Research Field
Professor
Radiation Biology
Masami WATANABE
Particle Radiation Oncology
Koji ONO
Area of Research
●
Cellular and molecular mechanism of radiation carcinogenesis
●
Molecular mechanism of stress response
●
Study of diagnosis and therapy using radiation (particle beam)
Research Field
Pathogenic Microbiology
Field Medicine
Professor
Area of Research
●
Distribution of bacterial and other pathogens in Asian and tropical environments
●
Epidemiology, diagnosis, and prevention of the infections by bacterial and other
pathogens in Asian and tropical environments
●
Association of the features of Asian and tropical environments with the trend of infections
by bacterial and other pathogens in these environments
●
Field Medica Study on Community-Dwelling Elderly in Japan
●
Field Medica Study on Community-Dwelling Elderly in Asia and Africa
●
Study on Neurodegenerative Diseases in New Guinea
Mitsuaki NISHIBUCHI
Kozo MATSUBAYASHI
Research Field List
Center for iPS Cell Research and Application (CiRA)
Research Field
Professor
Reprogramming Regulation Field
Differentiation Induction Field
Disease modeling with patientderived iPS cells
Area of Research
●
Functional analysis and discovery of reprogramming factors.
●
Gene expression analysis during direct reprogramming.
●
Evaluation of safeness of induced Pluripotent Stem cells.
●
Establishment of the efficient method for iPS cell generation.
●
Study of molecular mechanisms of differentiation from induced pluripotent stem (iPS)
cells into various tissue-specific cells including mesenchymal cells, caridovascular cells,
cells of central nervous systems, and cells of kidney and liver
●
Establishment of highly efficient and safe methods to induce differentiation
●
Establishment of disease-specific iPS cells
●
Pathophysiological study of various diseases such as the congenital diseases including
hematological disorders with bone marrow failure, primary immunodeficiency diseases,
refractory pediatric neurological diseases, and congenital hearing loss using iPS cells
●
Development of new drugs and cell therapies using iPS cells
Shinya Yamanaka
Junya Toguchida
Tatsutoshi Nakahata
Institute for Integrated Cell-Material Scienses (iCeMS)
Research Field
Professor
Develpomental Biology
Takashi HIIRAGI
Area of Research
●
Systems-level understanding of early mammalian development
●
Molecular mechanism of polarity establishment in the mouse embryo
●
Centrosome inheritance and transition from meiosis to mitosis
●
Cellular polarity establishment
●
Developmental clock
Affiliate Graduate School
Research Field
Professor
Medical Embryology
(RIKEN Center for Developmental
Biology)
Biology)
(Osaka Bioscience Institute)
Application Biology and
Regenerative Medicine
Biology)
Area of Research
●
Study of molecular mechanism of early central nervous development
●
In vitro study of nerve differentiation control
●
Study of regeneration medical application of nerve differentiation control
●
Molecular biological study of pattern formation in early embryo
●
Study of somatic cell nuclear reprogramming
●
Study of mammalian fertilization
●
Molecular mechanisms of synapse formation in the retina and brain
●
Molecular mechanisms of primary cilia formation and function in the CNS
●
Mechanisms of cell fate determination of the vertebrate retina
●
Functional analysis of microRNA expressed in the retina and brain
●
Generation of KO/transgenic mice and analysis of their visual function
●
Research about mechanism of neural regeneration in the central nervous system
●
Transplantation research of ES/iPS-derived cells
●
Genetic analysis and pathology research of retinal degenerative diseases
Yoshiki SASAI
Teruhiko WAKAYAMA
Takahisa FURUKAWA
Masayo TAKAHASHI
Kyoto University
Public Health
(Professional Degree Program / Doctoral Program)
Research Field
Professor
Biostatistics
Tosiya SATO
Epidemiology and Healthcare
Research
Genomic epidemiology
Healthcare Economics and
Quality Management
Medical Ethics and Medical
Genetics
Health Informatics
Shunichi FUKUHARA
Koji KAWAKAMI
Fumihiko MATSUDA
Yuichi IMANAKA
Shinji KOSUGI
Takeo NAKAYAMA
Medical Communication
Management of Technology and
Intellectual Property
Health and Environmental
Sciences
Health Promotion and Human
Behavior
Preventive Services
Global Health and Socioepidemiology
Public Health and International
Health
Area of Research
●
Epidemiologic methods
●
Clinical trials methods
●
Causal inference
●
Measurement and analysis of quality of care and outcomes
●
Quantitative evaluation of diagnostic measures
●
Study on clinical reasoning
●
●
Reseaches on clinical trials
●
Drug safety researches including pharmacoepidemiology and pharmacoeconomics
●
●
Hybrid peptide therapiy researches focusing cancer and inflammatory diseases
●
Identification of genetic factors related to human multifactorial diseases
●
Genetic epidemiology of community-based prospective genome cohorts
●
Development of database for the management of genomic studies
●
Policy and economics of health care
●
Management of healthcare organizations
●
Healthcare reform in policy and system
●
Quality, safety, efficiency and equity of health care and its improvement
●
Costing, pricing and performance measurement in health care
●
Study of ethical examination
●
Study of medical care policy
●
Study of medical care for heredity
●
Evidence-based healthcare
●
Health informatics and communication
●
Narrative and patient experiences
●
Interaction between medicine and society
●
Sociological analysis of medicine
●
Communication among health professionals
●
Study of management of intellectual property in medical science area
●
Study of technology transfer
●
Genetic epidemiology of lifestyle disorders
●
Risk evaluation of Persistent Organic Pollutants
●
Genetic epidemiology of preventable multifactorial diseases
●
Industrial toxicology
●
Behavioral medicine
●
Cognitive-behavior therapy of mood and anxiety disorders
●
Evidence-based mental health
●
Clinical epidemiology
●
Epidemiological analysis of disease development process
●
Development of preventive medical care
●
Epidemiology of HIV/AIDS&STD
●
Behavioral epidemiology of high risk populations for HIV infection
●
Socio-epidemiological study of prevention of HIV infection
●
Study of health policy
●
Study of international health
●
Study of health promotion and health education
●
Incidence and spread of infectious diseases in humans in Asia and developing countries
●
Environmental factors responsible for infectious diseases in humans in Asia and
developing countries
●
Association between incidence and spread of infectious diseases in humans with
environmental factors in Asia and developing countries
Hirokazu YAMAMOTO
Akio KOIZUMI
Toshiaki FURUKAWA
Takashi KAWAMURA
Masahiro KIHARA
Toshitaka NAKAHARA
Ecology with Emphasis on the
Environment
(Center for Southeast Asian
Studies)
Mitsuaki NISHIBUCHI
Field Medicine
(Center for Southeast Asian
Studies)
Kozo MATSUBAYASHI
●
Field Medica Study on Community-Dwelling Elderly in Japan
●
Field Medica Study on Community-Dwelling Elderly in Asia and Africa
●
Study on Neurodegenerative Diseases in New Guinea
Research Field List
Human Health Science
Nursing Science
Research Field
Professor
Environmental Health Nursing
Sawako SUGA
Human Body Defense & Pathophysiology Nursing Science
Nursing Science for LifestyleRelated Diseases
Psychiatric Nursing
Yumi SAITO
Shinichi NOMOTO
Kiminori HOSODA
Kazuko NIN
Child Health and Development
Nursing
Midwifery and Women's Health
Preventive Nursing
Home Healthcare Nursing
●
Study of living environment in nursing
●
Study of nursing counseling
●
Study of infection control nursing
●
Study of stress reduction for immuno compromised host
●
Development on the ubiquitous system for community health care
●
Reserch on liveable cities on the creation of urban health sciences
●
Study of nursing science for Lifestyle-Related Diseases
●
Study of Lifestyle-Related Diseases
●
Study of Pothography
●
Study of child and adolscent psychiatry
●
Study of researches on suicide nurcing
●
Study of development of new diagnostic imaging methods with NIRS,EEG ,etc for the
brain function
●
Study of support for families of children with development disabilities
●
Study of the support for social independence of mentally handicapped people at sheltered
workshops
●
Study of development of the cooperation system model for pregnant women with
psychiatric disorder
●
Study of critical care patients
●
Study of organ transplantation nursing care
●
Study of sense of coherence around critical care
●
Study of nursing of medically dependent children and their families
●
Longitudinal study on labor pain intensity and related factors
●
Study of pregnant/postpartum women who underwent fertility treatment and their partners
●
Developments of fetus phantoms and the educational guideline for ultrasound scan in the
midwifery diagnosis
●
Study of women’s health assessed by autonomic nervous system activity and infrared
thermography
●
Study of reproductive health/rights
●
Research on the international comparison of midwifery education
●
Reproducive Medicine Infertility Obstetrics and Gynecology Sexology
●
Cohort Study on prevention of lifestyle-related diseases and health behaviors
●
Study on successful aging and health promotion in a community
●
Study on building a healthy and safety town
●
Administrative study on health promotion strategy and community diagnosis
●
Study on prevention of falls of the erderly people
●
Study of pathogenesis of Alzheimer's disease
●
Development of IT-based home health care system
●
Analytical study of the stress of dementia patients' caregivers
Shigeru SAKURABA
Critical Care Nursing
Female Life-Cycle Nursing
Area of Research
Machiko SUZUKI
Kiyoko KABEYAMA
Nobuhiko SUGANUMA
Toshiki KATSURA
Ayae KINOSHITA
Kyoto University
Laboratory Science
Research Field
Professor
Area of Research
Basic Laboratory Science
Shogo OKA
Kuniaki SAITO
●
Study of biological information inherent in sugar chains
Innovational Laboratory Medicine
Tetsuya TAKAKUWA
●
Study of human embryo using MR imaging
●
Mechanisms of new type of cell death induced by molecular target therapy
●
Development of new treatments and new prognostic factors in child AML
●
Early diagnosis of pancreatobiliary malignancies
●
Conventional or rapid cytological examinations in digestive malignancies
●
Development of acceleration bed for improving QOL of elderly
●
Development of new quantitative neuroimaging techniques (Neurocalorimetry)
●
Developments of BMI technology based on EEG and NIRS
●
In vivo molecular imaging (BioSeeThrough Project)
●
Analyses of biosignals for understanding brain function
●
Development of imaging and image processing methods for quantitative analysis of multi
dimensional medical images including multi modality images or sequential images
●
Development of various medical applications such as computer aided diagnosis or
therapy system by using the above methods
●
Development of MR microscopy system (hardware and software)
●
Basic theory of non-invasive sensing and imaging of biomedical information
●
Development of novel medical modalities for diagnosis and minimally-invasive treatment
support
●
Advanced ultrasound and optical imaging technology and its clinical application
●
Medical image processing and computer-aided-diagnosis
Applied Laboratory Science
Medical Devices for Diagnoses
Innovative Medical Imaging
Technology
Medical Imaging System
Sciences
Souichi ADACHI
Akihiko NAKAIZUMI
Masatoshi FUJITA
Akitoshi SEIYAMA
Naozo SUGIMOTO
Tsuyoshi SHIINA
Research Field
Professor
Motor Function Analysis
Hiroshi KUROKI
Makoto ISHIBASHI
Development and Rehabilitation
of Motor Funcition
Clinical Cognitive Neuroscience
Brain Function and
Rehabilitation
Noriaki ICHIHASHI
Tadao TSUBOYAMA
Toshiko FUTAKI
Motomi TOICHI
Akira MITANI
Area of Research
●
Molecular mechanisms of morphogenesis during development of the central nervous
system, limb and cartilage
●
Study on rehabilitation for articuloar cartilage and knee osteoarthritis
●
Study of biomechanics and motor control of human movement
●
Clinical study on musculoskeletal disorders
●
Analysis of muscle function
●
Study on interventions for preventing falls in elderly
●
Study on rehabilitation for cancer patients
●
Rehabilitation on occupational behavior in functional disorder
●
Electrophysiological and neuroimaging study on cognition in psychiatric disorders
●
Neuroscience-based rehabilitation
●
Occupational therapy for mental disorders
●
Group dynamics and communication
Hiroshi YAMANE
Fusion Unit for Near Future Human Health Sciences
Research Field
Innovation Unit for Near Future
System and Technology
Professor
Hidenori ARAI
Area of Research
●
Prevention of falls
●
Prevention of the decline of ADL in frail elderly
●
Research on the effect of discharge planning on QOL of a patient and their family and on
the education tools for medical staffs
●
Effect of comprehensive geriatric assessment (CGA) during hospitalization on ADL and
QOL after discharge
- Basic Medicine (Core Departments) - Biological Sciences
Biological Sciences
Brain is the largest frontier in the biological research. Our laboratory has made a significant progress in brain research by using
various research tools. To make further progress and explore the new horizon in this field, power of flexible imagination of
young people is indispensable. We welcome young students to our laboratory and hope them working together to create new
aspects in brain research.
Dai Watanabe, M.D., Ph.D
Professor
❶
●
❷
●
Research and Education
Throughout recorded time, the human brain - a
spongy, 1.5 kilogram mass of fatty tissue - has
been compared to a telephone switchboard and a
supercomputer.
But the brain is much more complicated than any
of these devices, a fact scientists confirm almost
daily with each new discovery. The extent of brain's
capabilities is unknown, but it is the most complex
living structure known in the universe.
This single organ controls all body activities, ranging
from heart rate and sexual function to emotion,
learning and memory. The brain is even thought
to influence the response to disease of the immune
system and to determine, in part, how well people
respond to medical treatments. Ultimately, it shapes ●
❸
our thoughts, hopes, dreams and imagination. In
short, the brain is what makes us human.
Neuroscientists have the daunting task of deciphering
the mystery of this most complex of all machines:
how as many as a trillion nerve cells are produced,
grow and organize themselves into effective,
functionally active systems that ordinarily remain in
working order throughout a person's lifetime.
Our laboratory has made a significant contribution
in understanding brain function by utilizing numbers
of up-to-date techniques such as molecular cloning,
electrophysiology, gene manipulation of living
❶ Cajal-etzius cells in naonatal cerebral
❹
●
animals, behavioral analysis and gene profiling.
cortex.
Important in organized cortex
development.
❷ An Amacrine cell in retina.
E s s e n t i a l fo r v i s u a l i n fo r m a t o n
procesing.
❸ Glutamate receptor in Hippocampus.
Center of lear ning and memor y
formation.
❹ Staffs
Biological Sciences
Professor : Dai Watanabe
Associate
Professor : Yoshiaki Nakajima
TEL
: +81-75-753-4437
FAX
: +81-75-753-4404
e-mail
: [email protected]
URL
: http://www.phy.med.kyoto-u.ac.jp/
Recent Publications
1. Watanabe D, Nakanishi S.(2003) mGluR2 postsynaptically senses granule cell inputs at Golgi cell
synapses. Neuron;39(5):821-829
2. Yamamoto M, Wada N, Kitabatake Y, Watanabe D, Anzai M, Yokoyama M, Teranishi Y,
Nakanishi S.(2003) Reversible suppression of glutamatergic neurotransmission of cerebellar
granule cells in vivo by genetically manipulated expression of tetanus neurotoxin light chain. J.
Neurosci.;23(17):6759-6767.
3. Soda T, Nakashima R, Watanabe D, Nakajima K, Pastan I, Nakanishi S.(2003) Segregation and
coactivation of developing neocortical layer 1 neurons. J. Neurosci.;23(15):6272-6279.
- Basic Medicine (Core Departments) - Anatomical Science
Anatomy and Developmental Biology
Vertebrate body has quite complex structures, which are generated by the process called “morphogenesis”. The mechanism of
morphogenesis is still not well understood even in this post-genome era. Alternative splicing of pre-mRNA generates a highly
dynamic human proteome through networks of coordinated splicing events, and is regulated on tissu-specific stage-dependent
way.Our goal is to establish a new paradigm on the mechanism of morphogenesis from the view point of mRNA processing
regulation. We will also try to find chemical modifiers of mRNA splicing, which will be applicable for clinical therapy against
malignant tumors, virus infections and neuromuscular diseases caused by aberrant splicing. We welcome enthusiastic young
researchers who will challenge to open new fields of biology.
Masatoshi Hagiwara
Professor
1)Decipherment of splicing code
Recent whole genome sequence analyses revealed that
a high degree of proteomic complexity is achieved
with a limited number of genes. This surprising finding
underscores the importance of alternative splicing,
through which a single gene can generate structurally and
functionally distinct protein isoforms. Alternative splicing
events are dynamically regulated in developmental stagedependent and tissue specific manners. Pre-mRNAs contain
a ‘splicing code’ made up of loosely defined consensus
sequences that define the splice junctions and a bewildering
number and diversity of relatively short cis-acting elements
within exons as well as introns. To decipher the splicing
code, we have developed transgenic alternative splicing
reporter systems that enable us to visualize alternative
splicing events in living nematode. With this reporter
system, we have identified trans-acting factors and ciselements involved in the splicing regulation and found
some evolutionally conserved regulation mechanisms
of alternative splicing.We recently developed transgenic
reporter mice that enable us to visualize dynamic alternative
splicing events in single cell resolution.
2) Development of new drugs to cure RNA diseases
There is a growing awareness that misregulations of mRNA
processing are causative of many human diseases including
hereditary, inflammatory and tumorigenic diseases. Thus
new therapeutic approaches that target RNA processing
mechanisms are highly anticipated. We focused on the
mRNA splicing process, and have developed compounds
that alter the alternative splicing events or even reverse
some misregulated splicing events. Using splicing
reporter systems, we screen and select chemical modifiers
of splicing, examine their biological function during
developmental stages, and consider their applications to
crure hitherto intractable diseases.
3) Mathematical modeling of spontaneous pattern
formation process during mammalian development.
During vertebrate development, spontaneous pattern
formation (formation of pattern out of seemingly
homogeneous initial state) is frequently observed, such
as lung branching, limb skeletogenesis and skull suture
interdigitation. These processes are quite complex and we
cannot understand them by simply analyzing each gene
involved. We formulated mathematical models which
represents essential feature of these pattern formation
process, and are now trying to verify the models by
developing novel experimental methods.
Anatomy and Developmental Biology
Professor : Masatoshi Hagiwara
Associate
Professor : Takashi Miura
Research Associate
Professor : Naoyuki Kataoka
Assistant
Professor : Akihide Takeuchi, Kensuke Ninomiya
Research Assistant
Professor : Isao Kii, Yukiko Okuno
TEL
: +81-75-753-4341
FAX
: +81-75-751-7529
e-mail
: [email protected]
URL
: http://www.anat1dadb.med.kyoto-u.
ac.jp/Anat1DADB/TOP.html
Kyoto University
Recent Publications
1. Ogawa Y, Nonaka Y, Goto T, Ohnishi E, Hiramatsu T, Kii I, Yoshida M , Ikura T , Onogi H ,
Shibuya H , Hosoya T, Ito N, and Hagiwara M (2010) Development of a novel selective inhibitor
of the Down syndrome-related kinase Dyrk1A. Nature Commun.1, 86, doi:10.1038/ncomms1090
2. Kuroyanagi H, Ohno G, Sakane, H, Maruoka, H, and Hagiwara M (2010) Visualization and
genetic analysis of alternative splicing regulation in vivo using fluorescence reporters in transgenic
Caenorhabditis elegans. Nature Protoc. 5, 1495-1517.
3. Kondo S and Miura T (2010) Reaction-diffusion model as a framework for understanding
biological pattern formation. Science. 329(5999):1616-1620. Review.
4. Ohno, G., Hagiwara, M. and Kuroyanagi, H. (2008) STAR family RNA-binding protein ASD2 regulates developmental switching of mutually exclusive alternative splicing in vivo. Genes &
Dev., 22,360-374.
5. Ideue T, Sasaki Y, Hagiwara M and Hirose T. (2007) Introns play an essential role in splicingdependent formation of the exon junction complex. Genes & Dev., 21, 1993-1998.
6. Kaida D, Motoyoshi H, Tashiro E, Nojima T, Hagiwara M, Ishigami K, Watanabe H, Kitahara T,
Yoshida T, Nakajima H, Tani T, Horinouchi S and Yoshida M (2007) A novel cell cycle inhibitor
spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA. Nature
Chem. Biol., 3, 576-583.
7. Miura T, Hartmann D, Kinboshi M, Komada M, Ishibashi M, Shiota K, The cyst-branch difference
in developing chick lung results from a different morphogen diffusion coefficient, Mech. Dev. 126,
160-72 (2009)
- Basic Medicine (Core Departments) - Anatomical Science
The human body consists of 6 trillion cells with at least 210 distinct types. Each of these cells has its own unique character, and it
is essential for human life for these cells to develop, maintain themselves, and function appropriately. The essential information
code that defines a cell’s unique character is the epigenome, which refers to the whole-genome assembly of epigenetic
modifications of chromatin, including DNA methylation and a variety of histone modifications. It is the states of the epigenome
that determine the growth, differentiation, responses to external stimuli, aging, and diseased conditions of the cells in our body.
By using all the available methodologies in life science as well as by developing new ones, we are aiming to understand the basis
of epigenetic regulations and to appropriately control the growth, differentiation, and function of the cells in vitro.
Mitinori Saitou, M.D., Ph.D.
Professor
All of the diverse cell types in the body can be broadly
classed as either somatic or germline cells. In contrast
to somatic cells, which work to maintain the constant,
stable form and function of an individual organism’s body,
germ cells provide the faithfully replicated information
needed to establish subsequent generations of individuals.
In order to fulfill this role, these cells need to exhibit
certain unique properties, including the ability to undergo
epigenetic reprogramming, to divide meiotically, and to
revert (generally through fusion with another germline
cell) to a state of developmental totipotency and maintain
that totipotent state until the start of ontogeny. Research in
our laboratory is geared to elucidating the developmental
bases of germline function at the molecular levels from the
very earliest stages of germline development. Specifically,
our subjects of interest are the molecular mechanisms, at
the levels of both signaling and transcription, involved in
the formation of mouse primordial germ cells (PGCs), the
cellular progenitors of sperm and oocytes, the genome-wide
epigenetic reprogramming that takes place immediately
following PGC establishment, the development and
application of technologies to enable the analysis of
transcriptional regulatory networks at the single-cell level,
and ultimately, reconstitution of germ cell development in
vitro.
Our studies have so far shown that germ cell specification
in mice integrates three key events: repression of the
somatic program, reacquisition of potential pluripotency,
and genome-wide epigenetic reprogramming. We have
identified a PR-domain-containing protein, Blimp1 (also
known as Prdm1), as a critical factor for PGC specification.
Using a highly representative single-cell microarray
technology that we developed, we identified complex
but highly ordered genome-wide transcription dynamics
associated with PGC specification. This analysis not only
demonstrated a dominant role of Blimp1 for the repression
of the genes normally down-regulated in PGCs relative
to their somatic neighbors, but also revealed the presence
of gene expression programs initiated independently
from Blimp1. Among such programs, we identified
Prdm14, another PR-domain-containing protein, as a key
regulator for the reacquisition of potential pluripotency
and genome-wide epigenetic reprogramming. The
launch of the germ cell lineage in mice, therefore, is
orchestrated by two independently acquired PR domaincontaining transcriptional regulators, Blimp1 and Prdm14.
Furthermore, we have identified a signaling principle in
germ cell fate specification. Such studies may provide
fundamental information on the reconstruction of the germ
cell lineage from pluripotent stem cells in vitro.
Professor : Mitinori Saitou
Senior
Lecturer : Katsuhiko Hayashi
Assistant
Professor : Kazuki Kurimoto, Hiroshi Ohta
TEL
: +81-75-753-4335
FAX
: +81-75-751-7286
e-mail
: [email protected]
❶
●
❷
●
❶ Expression of Blimp1 and Prdm14 in mouse embryos at embryonic day 7.0.
❷ Sperm differentiated from induced primordial germ cells from the epiblasts engineered
to express GFP (left) are fertilization-competent and can be used to generate normal
offspring (right; green shows GFP fluorescence)
Recent Publications
1. Yabuta, Y., Ohta, H., Abe, T., Kurimoro, K., Chuma, S., and Saitou, M. (2011). TDRD5 is required
for retrotransposon silencing, chromatoid body assembly and spermiogenesis in mice. The Journal
of Cell Biology, in press.
2. Yamaji, M., Tanaka, T., Shigeta, M., Chuma, S., Saga, Y., and Saitou, M. (2010). Functional
reconstruction of Nanos3 expression in the germ cell lineage by a novel transgenic reporter reveals
distinct subcellular localizations of Nanos3. Reproduction, 139, 381-393.
3. Ohinata, Y., Ohta, H., Shigeta, M., Yamanaka, K., Wakayama, T., and Saitou, M. (2009). A
signaling principle for the specification of the germ cell lineage in mice. Cell, 137, 571-584.
4. Yamaji, M., Seki, Y., Kurimoto, K., Yabuta, Y., Yuasa, M., Shigeta, M., Yamanaka, K., Ohinata, Y.,
and Saitou, M. (2008). Critical function of Prdm14 for the establishment of the germ cell lineage in
mice. Nature Genetics, 40, 1016-1022.
5. Kurimoto, K., Yabuta, Y., Ohinata, Y., Shigeta, M., Yamanaka, K., and Saitou, M. (2008). Complex
genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell
lineage in mice. Genes & Development, 22, 1617-1635.
- Basic Medicine (Core Departments) - Physiology
We aim at clarifying the mechanisms underlying the cardiac cell function. So far, we examined the membrane excitation, muscle
contraction and their regulation on the molecular level. By implementing these experimental findings into a comprehensive
computer model, a variety of cell functions have been successfully reconstructed. Our educational policy is dependent on
motivation of individual students. To encourage their motivation, we spend more time in doing experiments than for surveying
literature. Students from different discipline are welcome to introduce natural sciences to medical study.
■Automaticiy of the heart
The heart, even if dissected out from the
experimental animal, can continue spontaneous
beat provided appropriate conditions such as ion
concentrations and oxygen supply. This automaticity
is due to a group of specialized muscle cells, called
pacemaker cells enbedded in the right atrium. We
isolate living pacemaker cells and apply the electrode
to measure its electrical activity. Now the activity of
pacemaker cells can be reconstructed on computer
based on experimental findings.
■Energy metabolism of the heart muscle.
The heart start its function to drive the blood
circulation at the early stage of embryo and continue
until the end of life. For the continusous heart
beat, it is essential for the heart cells to receive
both the nutrients and oxygen without any break.
The biological energy is produced mainly by
mitochondria and used by cell contraction and related
processes. We also aim at reconstructing these energy
metabolims on the computer model.
❷
●
■Computer modeling of Cell/Biodynamics
'Integration' is now our central task. We are
challenging to organize enormous body of
experimental evidence and bringing together many
classical discoveries on molecular as well as system
levels into a comprehensive dynamic biological
models. 'Integration' using the modern computer
technology will vastly change the paradigm of
present scientific researh as well as industrialization
process. The computerized mechanisms of biological
function will reconstruct versatile responses
of our body to various inputs such as variable
environmental changes, physiological conditions,
disease and drug administration.
Associate
Professor : Tamotsu Mitsuiye
Associate
Professor (JST) : Satoshi Matsuoka
Assistant
Professor : Ayako Takeuchi
TEL
: +81-75-753-4353
FAX
: +81-75-753-4349
e-mail
: [email protected]
URL
: http://www.card.med.kyoto-u.ac.jp/
Kyoto University
❶ An isolated pacemaker cell (left)
and the ventricular myocyte.
To the pacemaker cel, a patch
electrode is attached to record
its electrical activity. The vertical
bars indicate 20 micro m.
❷ The composition of our computer
model of a cardiac myocyte.
The model can reconstr uct
the membrane excitation, ionic
homeostasis, the contraction
a n d t h e AT P h o m e o s t a s i s
including the mitochondria.
❸ Staffs
❶
●
❸
●
Recent Publications
1. Matsuoka S, Sarai N, Jo H, Noma A. Simulation of ATP Metabolism in Cardiac ExcitationContraction Coupling. Progress in Biophysics and Molecular Biology, 85;279-299 (2004)
2. Cho HS, Takano M, Noma A. The electrophysiological properties of spontaneously beating
pacemaker cells isolated from mouse sinoatrial node. Journal of Physiology 550;169-180 (2003)
3. Matsuoka S, Sarai N. Kuratomi S, Ono K, Noma A. Role of individual ionic current systems in
ventricular cells hypothesized by a model study. Japanese Journal of Physiology 53;105-123 (2003)
4. Kuratome S, Matsuoka S, Sarai N, Powell T, Noma A. Involvement of Ca2+ buffering and Na+/
Ca2+ exchange in the positive staircase of contraction in guinea-pig ventricular myocytes. Pflugers
Archiv 446;347-355 (2003).
- Basic Medicine (Core Departments) - Bioregulation
Pharmacology
The cancer death rate is increasing every year, mostly due to invasion and metastasis. Accordingly, overcoming cancer invasion
and metastasis should be on top of the agenda in today's research. To this end, we will need a wide-range basic research
from molecular and cellular levels, to whole body studies aiming at novel therapeutic strategies. In our laboratory, we have
constructed many mouse models of gastrointestinal polyposis and cancer. Using such models, we have proven the role of
cyclooxygenase 2 (COX-2) in polyp formation and established the therapeutic strategy with COX-2 inhibitors. We are currently
pursuing studies focusing on mouse models of invasive and metastatic cancers. Because of years of experience in research in
USA by the principal investigator, special emphasis is placed on the graduate and postdoctoral training with international views.
Makoto Mark Taketo, M.D., Ph.D.
Professor
In our laboratory, we have constructed many
mouse tumor models, making extensive use of
the transgenic and gene knockout technology. For
example, we have constructed Apc-Δ(delta)716
knockout mice as a model for familial adenomatous
polyposis (FAP). In this model, we discovered
that COX-2 is induced at a very early stage, and
contributes to the expansion of the polyps. We have
also developed a mouse model of colon cancer
(adenocarcinoma) that shows strong invasion. Using
this model, we have recently reported that the cancer
epithelium, where the TGF-β(beta) family signaling
is inactivated, expresses a chemokine ligand and
attracts bone marrow-derived immature myeloid
cells that produce proteases and help the tumor
epithelium invasion. Based on these achievements,
we are currently pursuing the following research
projects.
❶
●
❷
●
1) Identification of genes that regulate malignant
progression
2) Role of iMCs in colon cancer invasion and
metastasis
3) Analysis of signaling pathways that are essential
for tumorigenesis
4) Pre-clinical study for cancer therapy
❶ Suppression of Colon
Cancer Metastasis by
Aes through Inhibition
of Notch Signaling
❷ Stimulation of colon
cancer invasion and
metastasis by immature
myeloid cells (iMCs)
In pursuing these research projects, we focus
on training of young scientists in a wide variety
of techniques in recombinant DNA technology,
embryonic stem cell culture and homologous
recombination, mouse embryo manipulation, mouse
genetics, histopathology, and pharmacology as well
as up-to-date knowledge in the related fields.
Recent Publications
Pharmacology
Professor : Makoto Mark Taketo
Senior
Lecturer : Masahiro Sonoshita
Assistant
Professor : Koji Aoki
TEL
: +81-75-753-4477
FAX
: +81-75-753-4402
e-mail
: [email protected]
URL
: http://www4.mfour.med.kyoto-u.ac.jp/
1. Sonoshita M, Aoki M, Fuwa H, Aoki K, Hosogi H, Sakai Y, Hashida H, Takabayashi A, Sasaki M,
Robine S, Itoh K, Yoshioka K, Kakizaki F, Kitamura T, Oshima M, Taketo MM. Suppression of
Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling. Cancer Cell 19:125-137,
2011.
2. Aoki K, Kakizaki F, Sakashita H, Manabe T, Aoki M, Taketo MM. Suppression of Colonic
Polyposis by Homeoprotein CDX2 through its Nontranscriptional Function that Stabilizes
p27Kip1. Cancer Res. 71:593-602, 2011.
3. Kakizaki F, Aoki K, Miyoshi H, Carrasco N, Aoki M, Taketo, MM. CDX transcription factors
positively regulate expression of solute carrier family 5, member 8 in the colonic epithelium.
Gastroenterology 138:627-635, 2010.
4. Arimura S, Matsunaga A, Kitamura T, Aoki K, Aoki M, Taketo MM. Reduced level of Smoothened
suppresses intestinal tumorigenesis by down-regulation of Wnt signaling. Gastroenterology
137:629-638, 2009.
5. Fujishita T, Aoki K, Lane HA, Aoki M, Taketo MM. Inhibition of the mTORC1 pathway
suppresses intestinal polyp formation and reduces mortality in ApcDelta716 mice. Proc. Natl.Acad.
Sci. U S A. 105:13544-13549, 2008.
- Basic Medicine (Core Departments) - Pathology and Tumor Biology
Since 1907 the department had focused on human pathology until 1998. In 1998, the standing point largely changed from human
pathology to molecular biology of diseases based on modern gene technology and cellular biology in mice and drosophila.
We Are Challenging Basic And Clinical Studies
Focusing On ASPDs In AD. To achieve a vibrant
aging society, we must understand the basic
mechansim and a fundermental cure for Alzheimer's
disease (AD). Amyloid β-protein (Aβ) assemblies
are thought to play primary roles in AD. Threre were
many challenges to establish antibody therapies,
based on the antibodies that targets multiple
types of Aβ assemblies. But clinical studies have
demonstrated side effects of those antibodies.
Recently, we identified ASPD, a possible cause of
neuronal cell death in AD patient, for the first time.
We also obtained the ASPD toxicity-neutralizing
antibodies(Noguchi et al, JBC2009).
Now we are trying to develop a therapeutic
application of ASPD antibodies and to understand
the molecular basis of ASPD formation, neuronal cell
death in AD.
❶
●
❷
●
❶ Immunoisolation
of ASPD
❷ The amount of
ASPDs correlates
with the desease
progression
Recent Publications
Associate
Professor : Minako Hoshi
Assistant
Professor : Shinji Itoh
TEL
: +81-75-753-4426
FAX
: +81-75-753-4676
URL
: http://lmls.med.kyoto-u.ac.jp
Kyoto University
1. Yoshida S., Sukeno M., Nabeshima Y. A Vascular-associated niche for undifferentiated
spermatogonia in the mouse testis. Science 317, 1722-1726 (2007)
2. Imura A., Tsuji Y., Murata M., Maeda R. Kubota K., Iwano A., Obuse C., Togashi K., Tominaga
M., Kita N., Tomiyama K., Iijima J., Nabehsima Y., Fujioka M., Asato R., Tanaka S., Kojima K., Ito
J., Nozaki K., Hashimoto N., Ito T., Nishio T., Uchiyama T., Fujimori T., Nabehsima Y. alfa-Klotho
as a regulator of Calcium homeostasis. Science 316, 1615-1618 (2007)
3. Kurotaki Y. Hatta K., Nakao K., Nabeshima Y., Fujimori T. Blastocyst axis is specified
independently of early cell lineage but aligns with the ZP shape. Science 316, 719-723 (2007)
4. Nakagawa T., Nabeshima Y., Yoshida S. Functional identification of the actual and potential stem
cell compartments in mouse spermatogenesis. Dev. Cell 12, 1-12 (2007)
5. Kawauchi T., Chhama K., Nabeshima Y., Hoshino M., Cdk5 phosphorylates and stabilizes
p27kip1, contributing to cortical neuronal migration. Nature Cell Biol. 8(1) 17-26 (2006)
6. Dezawa M., Ishikawa H., Itokazu Y., Yoshihara T., Hoshino M., Takeda S., Ide C., Nabeshima Y.
Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science 309,
314-317 (2005)
7. Hoshino M., Nakamura S. Mori K., Kawauchi T., Terao M., Nishimura Y.V., Fukuda A., Matsuo
N., Sone M., Terashima T., Wright C. V.E., Kawauchi Y., Nakao K., Nabeshima Y. ptf1a, a bHLH
transcription gene, defines GABAergic neuronal fates in cerebellum. Neuron 47, 201-213 (2005)
The Takeda Prize for Medical Science 2007
The Uehara Prize 2005
- Basic Medicine (Core Departments) - Basic Pathology
Pathology and Biology of Diseases
Pathology is the school of science that takes advantage of any methodology for the understanding of the diseases. Our laboratory
has been achieving many feats in the experimental oncology such as the discovery of Fujinami Sarcoma Virus, which was named
after the founder of our department, Professor Akira Fujinami. We succeed this tradition and attempt to decipher the enigma of
cancer development by using variety of techniques, which includes Fluorescence resonance energy transfer (FRET) imaging,
two-photon excitation fluorescence microscopy, and computer simulation.
Michiyuki Matsuda, M.D., Ph.D.
Professor
The basic concept of this department is the cancer
research based on the morphological methods.
We have been developing FRET probes for the
monitoring of oncogene products in living cells. The
first successful image of Ras activation reported in
2001 can be found in many textbooks of cell biology.
To date this research group has been developed
more than 20 probes for G proteins, kinases, and
phospholipids. These probes are used to visualize
the growth signal transduction cascades and to
collect parameters that determine the property of this
signaling system. Such parameters are invaluable in
that they provide the foundation of the virtual cancer
cells. Students in our department come from schools
of medicine, biology, physics, and so on. They are
enthusiastically learning not only modern molecular
biology and pathology, but also bioimaging and
system biology. We pay particular focus on the
teaching of English communication. Many students
present their data in the meetings abroad.
❶
●
❷
●
❸
●
❹
●
❶ Activity change of Rac1 GTPase
during cytokinesis of Hela cells
❷ Kinetic simulation model of Ras/
Raf/MEK/ERK cascade
❸ Simulation model of EGF
receptor signaling
❹ Video image of glioma cell
invasion into the brain
Recent Publications
Pathology and Biology of Diseases
Professor : Michiyuki Matsuda
Senior
Lecturer : Etsuko Kiyokawa
TEL
: +81-75-753-4697(office),
9450 (laboratory)
FAX
: +81-75-753-4655 (office),
4698 (laboratory)
e-mail
: [email protected]
[email protected]
URL
: http://www.lif.kyoto-u.ac.jp:80/labs/
fret/
1. Yoshiki,S., Matsunaga-Udagawa,R., Aoki,K., Kamioka,Y., Kiyokawa,E., and Matsuda,M. Ras and
calcium signaling pathwaysconverge at Raf1 via the Shoc2 scaffold protein. Mol. Biol. Cell. 21(6)
: 1088-96, 2010.
2. Elfenbein A, Rhodes JM, Meller J, Schwartz MA, Matsuda M, and Simons M. Suppression of
RhoG activity is mediated by a syndecan 4-synectin-RhoGDI1 complex and is reversed by PKC
alpha in a Rac1 activation pathway. J.Cell Biol. 186:75-83, 2009.
3. Kitano M, Nakaya M, Nakamura T, Nagata S, and Matsuda M. Imaging of Rab5 activity identifies
essential regulators for phagosome maturation. Nature 453:241-245, 2008.
4. Aoki K, Nakamura T, Inoue T, Meyer T, and Matsuda M. An essential role for the SHIP2dependent negative feedback loop in neuritogenesis of NGF-stimulated PC12 cells. J.Cell Biol.
177:817-827, 2007.
5. Kawase K, Nakamura T, Takaya A, Aoki K, Namikawa K, Kiyama H, Inagaki S, Takemoto H,
Saltiel AR, and Matsuda M. GTP hydrolysis by the Rho family GTPase TC10 promotes exocytic
vesicle fusion. Dev. Cell 11: 411-421, 2006.
- Basic Medicine (Core Departments) - Basic Pathology
The Department of Diagnostic Pathology was established in 1980, and has long been recognized as a branch laboratory of
investigative pathology and clinical pathology. Diagnostic pathology is a clinical application of proteomics and cellular
pathology, contributing to determination of treatment strategy and evaluation of effects of treatment. In accordance with
reorganization of the departments of investigative pathology, our department is now responsible for all autopsies and education
of systemic pathology for undergraduate students as well as examination and interpretation of surgical specimens and
cytopathological specimens in Kyoto University.
Hironori Haga
Professor
Members of the department are experts in surgical
pathology of several organs and some specific
diseases. They pursue individual research projects
in close cooperation with clinicians and other
biomedical researchers. Most of our researches
are clinically oriented, and our goal is to provide
accurate and scientific diagnosis based on histology
and cytology.
Current clinical researches include 1) analysis of
allograft rejection and other complications after
organ transplantation, 2) diagnosis of rare cervical
cancers, 3) study on IgG4-related systemic diseases.
Other current and previous study included analysis
of duodenal cancer, lung cancer, bone tumors, and so
on. More basic themes are 1) elucidation of JAK2/
STAT5 pathway in development of hematologic
malignancies, 2) chimerism and senescence of
the liver allograft, and 3) treatment of mast cell
disorders. In addition to these studies initiated by
pathology members, we are involved in several
projects lead by clinicians.
Education for graduate students is combination
of research and advanced training for diagnostic
pathology. Subspecialty training for surgical
pathology or cytopathology is encouraged in
combination with basic investigative research
and/or traditional pathology study using
immunohistochemistry and in situ hybridization.
Complete in-house digital pathology database and
image analysis using virtual microcopy are also
available.
❶
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❸
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❷
●
❶ Endothelial chimer ism.
Original donor endothelium
(green) mixed with
recipient-derived
endothelial cells (brown)
reflecting por tal fibrosis
and neovessel formation.
❷ C4d-positive chronic
rejection after liver
transplantation.
❸ IgG4-related lung disease
showing vasculitis with
IgG4-positive plasma cells.
❹ Staffs.
❹
●
Recent Publications
Professor : Hironori Haga
Associate
Professor : Yoshiki Mikami, Sachiko Minamiguchi
Senior
Lecturer : Aya Miyagawa-Hayashino
Assistant
Professor : Shinji Sumiyoshi
TEL
: +81-75-751-3488
FAX
: +81-75-751-3499
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/
~pathology/index.html
Kyoto University
1. Tsuruyama T, Nakai T, Hiratsuka T, Jin G, Nakamura T, Yoshikawa K. In vitro HIV-1 selective
integration into the target sequence and decoy-effect of the modified sequence. PLoS One.
2010;5:e13841.
2. Miyagawa-Hayashino A, Egawa H, Yorifuji T, Hasegawa M, Haga H, Tsuruyama T, Wen MC,
Sumazaki R, Manabe T, Uemoto S. Allograft steatohepatitis in progressive familial intrahepatic
cholestasis type 1 after living donor liver transplantation. Liver Transpl. 2009;15:610-8.
3. Mikami Y, Kiyokawa T, Sasajima Y, Teramoto N, Wakasa T, Wakasa K, Hata S. Reappraisal of
synchronous and multifocal mucinous lesions of the female genital tract: a close association with
gastric metaplasia. Histopathology. 2009;54:184-91.
4. Fujimoto M, Haga H, Okamoto M, Obara E, Ishihara M, Mizuta N, Nishimura K, Manabe T. EBVassociated diffuse large B-cell lymphoma arising in the chest wall with surgical mesh implant.
Pathol Int. 2008;58:668-71.
5. Yamashita K, Haga H, Kobashi Y, Miyagawa-Hayashino A, Yoshizawa A, Manabe T. Lung
involvement in IgG4-related lymphoplasmacytic vasculitis and interstitial fibrosis: report of 3 cases
and review of the literature. Am J Surg Pathol. 2008;32:1620-6.
- Basic Medicine (Core Departments) - Infectious Diseases and Immunology
Microbiology
The clinical outcome of infection is the result of a battle between bacterial virulence factors and the host defense system. It is
becoming increasingly important to understand the basic mechanism of bacteria-host interaction under the current situation
where bacteria acquire antibiotic resistance. We have been particularly interested in the intracellular parasitic bacteria that
are capable of escaping the macrophage killing. Our aim is to elucidate the molecular mechanism of survival of Listeria and
Mycobacteria, representative intracellular parasitic bacteria, and the host immune response to these microbes.
Masao Mitsuyama, M.D., Ph.D.
Professor
❶ Construction of recombinant
❶
●
L. monocytogenes strains
1. Virulence factor of Listeria and the host response
differing in hly gene, the
The ability of Listeria monocytogenes to evade the
growth of each strain
inside macrophages
intracellular killing by macrophages depends mainly
(immunofluorescence
on its virulence locus called LIPI-1. By constructing
microscopy) and the
the deficient mutant for the genes locating in this
ability to induce caspase-1
locus, we have found that LLO encoded by hly
activation (western blotting).
plays a critical role in the induction of host cytokine
❷2 RD1 region of M.
tuberculosis plays an
response in addition to its role for cytosolic invasion.
essential role in the
The precise relationship between the LLO structure
induction of host cell
and the cytokine-inducing ability has been analyzed
necrosis, processing and
and reported. Our current research is trying to
secretion of IL-1a and IL-1b
clarify the molecular mechanism in inflammasome
in infected macrophages.
❸ Lab Staffs (as of February,
formation and induction of type I interferon in
2011)
infected macrophages by using construction of
various mutant or recombinant strains, mice deficient
❷
●
❸
●
for candidate genes or SiRNA.
2. Virulence factor of Mycobacteria and the host
response
One of the major candidates for the virulence of
M. tuberculosis is RD1 locus that encodes various
protein probably comprising a type VII secretion
system. By using RD1 deficient mutant and
complemented strains, we have found that RD1 is
involved in the host cell necrosis and induction of
IL-1α,β processing. We are now trying to find out
how the effector proteins encoded by RD1 locus
induce such response of host macrophages. Another
candidate is PPE proteins in one of which we have
found the inhibitory activity for host cytokine
response. Our recent studies have revealed that
PD1/PDL-1 pathway of the host plays a pivotal
role in the pathophysiology of infected mice. Thus,
mycobacterial virulence factors and host response are
under investigation from a various point of view.
As our laboratory has a number of students from
Recent Publications
abroad, we use English at our journal club or data
1. Hara H, Tsuchiya K, Nomura T, Kawamura I, Shoma S & Mitsuyama M : Dependency of
discussion.
caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, Listeriolysin
Microbiology
Professor : Masao Mitsuyama
Associate
Professor : Ikuo Kawamura
Assistant
Professor : Kohsuke Tsuchiya, Hideki Hara
TEL
: +81-75-753-4441, 4448
FAX
: +81-75-753-4446
e-mail
: [email protected]
URL
: http://bisei15.mb.med.kyoto-u.ac.jp/
index.html
O, after evasion from phagosome into the cytoplasm. J. Immunol. 180: 7859-7868, 2008.
2. Kurenuma T, Kawamura I, Hara H, Uchiyama R, Daim S, Dewamitta SR, Sakai S, Tsuchiya K,
Nomura T & Mitsuyama M. : RD1 locus in Mycobacterium tuberculosis genome contributes to
activation of caspase-1 via induction of potassium ion efflux in infected macrophages. Infect.
Immun. 77: 3992-4001, 2009.
3. Tsuchiya K, Hara H, Kawamura I, Nomura T, Yamamoto T, Daim S, Dewamitta SR, Shen Y,
Fang R, & Mitsuyama M. : Involvement of absent in melanoma 2 in inflammasome activation in
macrophages infected with Listeria monocytogenes. J. Immunol. 185: 1186-1195, 2010.
4. Dewamitta SR, Nomura T, Kawamura I, Hara H, Tsuchiya K, Kurenuma T, Shen Y, Daim S,
Yamamoto T, Qu H, Sakai S, Xu Y & Mitsuyama M. : Listeriolysin O-dependent bacterial entry into
the cytoplasm is required for calpain activation and interleukin-1 alpha secretion in macrophages
infected with Listeria monocytogenes. Infect. Immun. 78 : 1884-1894,2010.
5. Sakai S, Kawamura I, Okazaki T, Tsuchiya K, Uchiyama R & Mitsuyama M.: PD-1-PD-L1
pathway impairs Th1 immune response in the late stage of infection with Mycobacterium bovis
bacillus Calmette-Guérin. Int. Immunol. 22: 915-925, 2010.
- Basic Medicine (Core Departments) - Infectious Diseases and Immunology
Immunology constitutes an essential part in almost every field of modern medicine, and understanding of immune mechanisms
has greatly contributed to the medical progress in many aspects. Despite the amazing advances in immunology for recent
decades, however, major immunological issues remain to be unveiled, and immunology continues to be one of the most
mysterious and challenging fields in modern biology and medicine. Research efforts in our laboratory are focused on
understanding the central issues in immunology, including the development of immune system, mechanisms of tumor immunity,
autoimmunity and leukemia development.
Nagahiro Minato, M.D., Ph.D.
Professor
Current major research activities in the laboratory
are focused on two aspects; first, understanding of
the mechanisms and regulation of normal immune
system and elucidating how dysregulation of normal
development leads to life-threatening diseases
such as autoimmune diseases, immunodeficiency
and leukemia; second, understanding of the
mechanisms of possible immune surveillance
against autonomously arising malignant cells and
applying the principles for effectively controlling
human cancer. We are studying these crucial issues
with the use of feasible animal models including
gene-engineered animals in close conditions to
“reality” as much as possible. Our key word is “
nature, but not we, decides the way to go”. This
laboratory is primarily responsible for the education
of Immunology for both undergraduate and graduate
students of Kyoto University School of Medicine.
There are many graduate students at Master and PhD
courses of both Graduate School of Medicine and
Graduate School of Biostudies, including foreign
students, and they are included in several specific
research projects under the instruction of 4 faculty
staff members with regular English-based laboratory
meetings.
❶
●
❷
●
❸
●
❶ Myeloproliferative disorders by deregulated Rap signaling (from cover page of Cancer
Cell)
❷ Development thymic epithelial cells (from Nature Immunol.)
❸ Laboratory members
Recent Publications
Professor : Nagahiro Minato
Associate
Professor : Yasutoshi Agata, Yoko Hamazaki
Assistant
Professor : Yasuhiro Nakashima
Program-Specific Associate
Professor : Yoshimasa Tanaka
TEL
: +81-75-753-4659
FAX
: +81-75-753-4403
e-mail
: [email protected]
URL
: http://www.imm.med.kyoto-u.ac.jp/
home_en.htm
Kyoto University
1. Kawai. K. Hamazaki, Y., Fujita, H., Fujita, A., Sato, T., Moriwaki, K., Furuse, M. , Fujimoto,
T., Agata, Y. and Minato, N. (2011) Claudin-4 is induced in thymocytes of late CD4/CD8 double
positive stage by E2A and promotes alpha BetaT cell receptor–mediated positive selection. Proc.
Nat. Acad. Sci. USA. in the press.
2. Shimatani, K., Nakashima, Y., Hattori, M., Hamazaki, Y., and Minato, N. (2009) Memory
phenotype PD-1+ CD4+ T cells expressing C/EBP alpha underlie T cell immunodepression in
senescence and leukemia. Proc. Nat. Acad. Sci. USA. 106;15807-15812.
3. Hamazaki, Y, Fujita, H, Kobayashi, T, Choi, Y, H. Scott, Matsumoto, M, and Minato, N. (2007)
Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from claudinexpressing cells. Nature Immunol. 8:304-311.
4. Minato, N, K. Kometani, and M.Hattori. (2007) Regulation of immune responses and
hematopoiesis by the Rap1 signal. (Review) Adv. Immunol. 93: 229-264.
5. Ishida, D., Su, L., Shinozuka, Y., Tamura,A., Katayama, Y., Kawai, Y., Wang, S-F, Taniwaki, M.,
Hamazaki, Y., Hattori, M., and Minato, N. (2006) Rap1 Signal Controls B Cell Receptor Repertoire
and Generation of Self-reactive B1 Cells. Immunity, 24,417-427.
- Basic Medicine (Core Departments) - Legal Medicine
Forensic Medicine and Molecular Pathology
The Department of Forensic Medicine and Molecular Pathology at Kyoto University has a proud legacy which can be traced
back to 1899 when the Department was first founded. Since its establishment, the Department has been an active force in
promoting the significance and importance of forensic medicine through innovative programs, educational initiatives, research
and analysis and advocacy for better forensic practices, policies and laws.
Keiji Tamaki, M.D.,
Professor
Our department is engaged in a number of ongoing research
projects which encompasses a wide range of topics with
DNA polymorphisms and genomic DNA rearrangement at
its core. While numerous in amount, our efforts are currently
concentrated on three major themes: screening/analyzing
mutations which occur during chromosomal crossover
events in germline cells; dissecting the depth and breadth of
microsatellite instability in the B-cell lymphoblastic lymphoma
genome; and elucidating the role of retrovirus and transposon
integration in promoting somatic cell mutations.
Minisatellite Analysis
The discovery and evolution of microsatellite-based analytical
techniques has all but marginalized minisatellite research,
however one of the defining characteristics of the human
genome—which distinguishes it from other primates—is the
highly polymorphic nature of minisatellites. Minisatellites
are commonly observed in and around telomeric regions in
eukaryotic genomes, and consist of arrays of widely dispersed
6-to 100-bp repeats. While other highly polymorphic regions
(microsatellites or STRs) are exploited for use in such avenues
as individual identification and paternity testing in the realm
of forensics, the groundwork for our forensic and population
genetic research endeavors is based on minisatellites.
Retroviruses and Pathological Research
To augment our existing arsenal, we have expanded our
activities to address the issues at the core of modern
microbiological research. In collaboration with a number of
globally renowned departments of basic medicine, we have
expanded our efforts to include identifying the retroviral
mechanisms underlying lymphomagenesis; erecting the
framework for individual identification techniques utilizing
in situ hybridization with probes; development of novel
strategies in differential diagnosis based on enhanced
immunohistochemical methods along with its application to
identifying chimerisms in acute and chronic allograft rejection;
molecular evaluation on the activation of antigen presenting
cells (APCs); and exploiting immunocompetent cell response as
a prognostic factor in colorectal cancer (CRC).
Autopsy Imaging (AI) and Training
In addition to research in basic medicine, we are one of the
pioneering institutes to initiate research in the revolutionary
field of Autopsy Imaging. In the near future, we hope to include
routine diagnostic imaging to our forensic autopsies in order to
identify the natural and/or external factors which contributed to
the death of an individual.
Autopsies remain a critical component of the services we
provide to the community. In order to meet the demands
for future forensic pathologists, we’ve erected an integrated
training initiative in collaboration with the Department of
Diagnostic Pathology, Kyoto University Hospital. Under this
program, post-graduate students receive intensive training in
Surgical Pathology to supplement their research and clinical
commitments.
Forensic Medicine and Molecular Pathology
Professor : Keiji Tamaki
Associate
Professor : Tatsuaki Tsuruyama
Assistant
Professor : Munetaka Ozeki, Hirokazu Kotani
TEL
: +81-75-753-4474
FAX
: +81-75-761-9591
e-mail
: [email protected]
URL
: http://square.umin.ac.jp/kyo_houi/
index.html
❶
●
❷
●
❸
●
❶ Example of minisatellite allele mapping via MVR-PCR
❷ Distribution of the likelihood ratio in sibship assessment utilizing varying numbers of
alleged siblings
❸ Model of STAT5A signal transduction pathway in B-cell lymphoblastic lymphoma
❹ Autopsy room equipped with the latest digital equipment
❺ Photo of Department members taken during cherry blossom season
❹
●
❺
●
Recent Publications
1. Tsuruyama T, Hiratsuka T, Jin G, Imai Y, Takeuchi H, Maruyama Y, Kanaya K, Ozeki M,
Takakuwa T, Haga H, Tamaki K, Nakamura T. MLV integration indeces the formation of
transcription factor complexes on palindromic sequences in the Stat5a gene during the development
of pre-B lymphomagenesis. Am J Pathol. 2010 (in press)
2. Yoshida K, Yayama K, Hatanaka A, Tamaki K. Efficacy of extended kinship analyses utilizing
commercial STR kit in establishing personal identification. Legal Med 2011;13:12-5
3. Tsuruyama T, Nakai T, Hiratsuka T, Jin G, Nakamura T, Yoshikawa K. In vitro HIV-1 integration
into the target sequence and decoy-effect of the modified sequence. PLsS One 2010;5(11):e13841.
4. Tsuruyama T, Imai Y, Takeuchi H, Hiratsuka T, Maruyama Y, Kanaya K, Kaszynski R, Jin G,
Okuno T, Ozeki M, Nakamura T, Takakuwa T, Manabe T, Tamaki K, Hiai H. Dual retrovirus
integration tagging: identification of new signaling molecules Fiz1 and Hipk2 that are involved in
the IL-7 signaling pathway in B lymphoblastic lymphomas. J Leukoc Biol. 2010;88(1):107-16.
5. Kaszynski RH, Akatsuka S, Hiratsuka T, Jin G, Ozeki M, Okuno T, Nakamura T, Manabe T,
Takakuwa T, Hiai H, Toyokuni S, Tamaki K, Tsuruyama T. A quantitative trait locus responsible
for inducing B-cell lymphoblastic lymphoma is a hotspot for microsatellite instability. Cancer Sci.
2010;101(3):800-5.
6. Shibasaki S, Imagawa A, Tauriainen S, Iino M, Oikarinen M, Abiru H, Tamaki K, Seino H, Nishi
K, Takase I, Okada Y, Uno S, Murase-Mishiba Y, Terasaki J, Makino H, Shimomura I, Hyöty
H, Hanafusa T. Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1
diabetes. Endocr J. 2010;57(3):211-9.
- Basic Medicine (Core Departments) - Molecular Medicine
Medical Chemistry
Science is a fun. We hope that members in our Department have a full of curiosity to science, work hard, and enjoy Science.
Using various techniques of Biochemistry and Molecular Biology, we are trying to unveil the mystery in life. Our devotion
to science would contribute to the understanding of human diseases. Following the tradition of our Department that had been
created by Former Professors Torasaburo Araki, Osamu Hayaishi, Tasuku Honjo, and others, we wish to create a new wave in
Medical Chemistry.
Shigekazu Nagata, Ph.D.
Professor
In our laboratory, we are studying the molecular
mechanism of cell death, and its physiological and
pathological roles. We identify molecules that are
involved in cell death, and characterize them using
techniques of Biochemistry, Molecular Biology,
and mouse Genetics. We identified Fas ligand, a
cytokine, that induces apoptosis in cells, and showed
that apoptosis is executed by caspases (proteases)
and CAD (caspase-activated DNase). Inefficient
apoptosis by lack of the Fas ligand or its receptor Fas
causes lymphoproliferation, leading to autoimmune
diseases. Whereas, the excessive apoptosis by Fas
ligand causes tissue destruction such as hepatitis.
Apoptotic dead cells are swiftly engulfed by
macrophages and degraded in lysosomes. We
identified proteins (MFG-E8 and Tim-4) that is
involved in engulfment of apoptotic cells, and
showed that if apoptotic cells are not efficiently
engulfed, they undergo secondary necrosis,
leading to SLE (systemic lupus erythematosus)type autoimmune diseases. We also identified an
enzyme (DNase II) that digests chromosomal DNA
of apoptotic cells after macrophage engulf them. If
macrophages cannot digest DNA, they are activated
and produce various cytokines including IFNb(beta)
and TNFa(alpha), causing severe anemia or chronic
polyarthritis. Phospholipids on plasma membranes
are asymmetrically distributed between inner and
outer leaflets. When cells undergo apoptosis, or
platelets are activated, this asymmetrical distribution
is disrupted, and phosphatidylserine exposed on
the cell surface functions as an “eat me” signal, or
trigger the blood clotting. We recently identified an
enzyme (scramblase) that causes the exposure of
phosphatidylserine on the activated platelets.
❶
●
❷
●
❸
●
❹
●
❶ MFG-E8-/- mice(-/-) show
the enlarged and activated
ger minal centers (PNApositive area), produce autoantibodies, and develop
SLE-type autoimmune
disease.
❷ DNase II-/- mice develop
chronic polyarthritis.
❸ The structure of TMEM16F
that catalyzes scrambling of
phospholipids on the plasma
membranes
❹ Members of the Department.
Recent Publications
Medical Chemistry
Professor : Shigekazu Nagata
Assistant
Professor : Rikinari Hanayama, Jun Suzuki
TEL
: +81-75-753-9441,
+81-75-753-9445
FAX
: +81-75-753-9446
e-mail
: [email protected]
URL
: http://www2.mfour.med.kyoto-u.
ac.jp/~nagata/
Kyoto University
1. Yoshida, H., Kawane, K., Koike, M., Mori, Y., Uchiyama, Y. and Nagata, S.: Phosphatidylserinedependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature 437: 754758, 2005.
2. Kawane, K., Ohtani, M., Miwa, K., Kizawa, T., Kanbara, Y., Yoshioka, Y., Yoshikawa, Y. and
Nagata, S.: Chronic polyarthritis caused by mammalian DNA that escapes from degradation in
macrophages. Nature 443: 998-1002, 2006.
3. Miyanishi, M., Tada, K., Koike, M., Uchiyama, Y., Kitamura, T. and Nagata, S.: Identification of
Tim-4 as a phosphatidylserine receptor. Nature 450: 435-439, 2007.
4. Okabe, Y., Sano, T. and Nagata, S.: Regulation of the innate immune response by threonine
phosphatase of Eyes absent. Nature 460: 520-524, 2009.
5. Suzuki, J., Umeda, M., Sims, P. J., and Nagata, S.: Calcium-dependent phospholipid scrambling by
TMEM16F. Nature 468: 834-838, 2010.
- Basic Medicine (Core Departments) - Molecular Medicine
Cell Biology
Membrane proteins govern the basic cellular processes of signal transduction,the generation of electrical signals, molecular
transport and energy conservation. In spite of the abundance and importance of membrane proteins there are only ca 120 unique
membrane protein structures have been determined. Our laboratory is studying the structures of various membrane proteins
and developing the methodologies in membrane protein crystallography in cooperation with ERATO Iwata Human Receptor
Crystallography Project(http://cell.mfour.med.kyoto-u.ac.jp), the MPL group at British synchrotron radiation facility, Diamond,
and the MPC group(http://www3.imperial.ac.uk/lifesciences/research/molecularbiosciences/membraneproteincrystallography)
at Imperial College London. Our laboratory is ideal for the students aspired to build up an international career.
So Iwata,Ph.D
Professor
The results of various genome projects have shown
that up to 30% of human proteins occur in cell
membranes. Membrane proteins play crucial roles in
many biological functions and are of key importance
for medicine. Over 50% of commercially available
drugs target membrane proteins.
We are currently focusing to determine medically
relevant membrane protein structures. These are the
G protein-coupled receptors (GPCR), transporters
(especially those for drugs, peptides, and sugars) and
enzymes involved in steroid synthesis or metabolism.
These membrane protein structures will provide a
basic understanding of life at the molecular level
and could boost computer aided rational design of
new drugs, which could reduce the number of animal
experiments and unwanted side effects.
❶
●
❶ Crystal structure of lactose
permiase from Escherichia coli. A
homologue of glucose transporters
implicated in diabetes
❷
●
❷ Crystal structure of Photosystem
II from Ther mosynechococcus
elongates. Split water molecules
u s i n g s o l a r e n e r g y t o evo l ve
molecular oxygen in the
atmosphere.
Graduate students in our laboratory are expected to
learn a series of techniques of protein crystallography
from expression to X-ray crystallographic analysis
and to solve a protein structure. The targets will be
those listed above or related proteins. These projects
are challenging but designed to be completed within
a few years.
Recent Publications
Cell Biology
Professor : So Iwata
Senior
Lecturer : Takuya Kobayashi
Assistant
Professor : Makoto Adachi, Norimichi Nomura
TEL
: +81-75-753-4372
FAX
: +81-75-753-4660
e-mail
: [email protected]
URL
: http://cell.mfour.med.kyoto-u.ac.jp/
1. Horsefield, R, Yankovskaya, V, Sexton, G, Whittingham, W, Shiomi, K, Omura, S, Byrne, B,
Cecchini, G, Iwata, S. (2006) Structural and computational analysis of the quinone-binding site of
complex II (succinate-ubiquinone oxidoreductase): a mechanism of electron transfer and proton
conduction during ubiquinone reduction. (2006) J. Biol. Chem. 281(11) 7309 – 7316
2. Mirza, O, Guan, L, Verner, G, Iwata, S, Kaback, HR. Structural evidence for induced fit and a
mechanism for sugar/H+ symport in LacY. (2006) EMBO J. 25(6) 1177 - 1183
3. Makyio, H, Iino, R, Ikeda, C, Imamura, H, Tamakoshi, M, Iwata, M, Stock, D, Bernal, RA,
Carpenter, EP, Yoshida, M, Yokoyama, K, Iwata, S. (2005) Structure of a central stalk subunit F of
prokaryotic V-type ATPase/synthase from Thermus thermophilus, EMBO J. 24(22) 3974 – 3983
4. Ferreira, KN, Iverson, TM, Maghlaoui, K, Barber, J, Iwata, S. Architecture of the photosynthetic
oxygen-evolving center (2004) Science 303(5665) 1831 - 1838
5. Abramson J, Smirnova I, Kasho V, Verner G, Kaback HR, Iwata S. (2003) Structure and
mechanism of the lactose permease of Escherichia coli Science 301(5633) 610-615
- Basic Medicine (Core Departments) - Molecular Biology
Molecular Oncology
Cancer originates from a small number of normal cells (often a single cell) in the body that progressively acquire un-controllable,
proliferative potentials and eventually form tumors. Cancer is sometimes called “disease of the cell” or “disease of genes”, since
cancer-derived cells have some properties distinguishable from those of normal counterparts and since these special properties
can be attributed to genetic alterations or mutations. Molecular Oncology is the research field where scientists try to discover
molecules (and their alterations) underlying the malignant behaviors of cancer cells, to elucidate their functions, and to utilize the
knowledge and materials obtained from such studies in developing effective methods of cancer therapy. The main focus of our
research group is to find and characterize molecules that play important roles in the malignant behaviors of cancer cells such as
recruitment of capillary blood vessels (or angiogenesis), invasion, and metastasis.
Makoto Noda, Ph.D.
Professor
It has been know for more than 30 years that cell
hybrids between normal cells and cancer cells show
non-malignant phenotype. It was also found that
the DNA extracted from cancer cells can confer
malignant phenotype when introduced into normal
cells. These apparently conflicting findings are
considered today to indicate the presence of multiple
types of mutations in cancer cells: i.e., inactivation
of tumor suppressor genes and activation of cancercausing genes (or oncogenes).
Through screening the genes with ability of
normalizing the malignant phenotype of cancer cells,
we have discovered RAP1A and RECK. RECK is
decreased in many kinds of solid tumors, and when
artificially expressed, it inhibits the ability of cancer
cells to invade, metastasize, and recruit blood vessels
(angiogenesis). Hence, our study of RECK may
help developing new diagnostic and therapeutic
methods. We have also shown that RAS oncogenes
may be involved in differentiation and even tumor
suppression depending on cell type. Through
screening of genes up-regulated in early stages of
brain development, we have discovered several novel
molecules with interesting bio-activities such as
Nedd2/caspase-2 (a protease executing apoptosis),
Nedd4 (ubiquitin ligase), Nedd5/Sept2 (novel
cytoskeletal protein involved in cell division), and
Nedd8 (ubiquitin-related protein modifier).
In a friendly and inspiring atmosphere, graduate
students with various backgrounds (including several
foreign fellows) are struggling to solve the important
puzzles of how cancer cells behave selfishly and how
they can be tamed.
❶ Activated RAS oncogenes
induce neuronal
differentiation in PC12 cells
(Nature 318: 73-75, 1985).
❷ RAP1A/Krev1 encoding
a low molecular weight
G-protein was discovered
as a transfor mation
suppressor gene against an
activated RAS oncogene
(Cell 56: 77-84, 1989).
❸ Another transfor mation
suppressor gene RECK
encodes a membraneanchored regulator of
matrix metalloproteinases
(MMP). RECK is downregulated in many cancers
and suppresses tumor
angiogenesis, invasion, and
metastasis when expressed
in such cancer cells (PNAS
95, 13221-13226, 1998;
Cell 107: 789-800, 2001).
❹ Laboratory members
❶
●
❷
●
❸
●
❹
●
Recent Publications
Molecular Oncology
Professor : Makoto Noda
Associate
Professor : Hitoshi Kitayama
Assistant
Professor : Tomoko Matsuzaki, Yoko Yoshida
TEL
: +81-75-751-4150
FAX
: +81-75-751-4159
e-mail
: [email protected]
URL
: http://www.users.iimc.kyoto-u.ac.jp/
~z59192/
Kyoto University
1. Wang H, Imamura Y, Ishibashi R, Chandana EP, Yamamoto M, Noda M. The Reck tumor
suppressor protein alleviates tissue damage and promotes functional recovery after transient
cerebral ischemia in mice. J Neurochem 115, 385-398 (2010).
2. Shamma A, Takegami Y, Miki T, Kitajima S, Noda M, Obara T, Okamoto T, Takahashi C. Rb
Regulates DNA damage response and cellular senescence through E2F-dependent suppression of
N-ras isoprenylation. Cancer Cell 15, 255-269 (2009).
3. Omura A, Matsuzaki T, Mio K, Ogura T, Yamamoto M, Fujita A, Okawa K, Kitayama H, Takahashi
C, Sato C, Noda M. RECK forms cowbell-shaped dimers and inhibits matrix metalloproteinasecatalyzed cleavage of fibronectin. J Biol Chem 284, 3461-3469 (2009).
4. Morioka Y, Monypenny J, Matsuzaki T, Shi S, Alexander DB, Kitayama H, Noda M. The
membrane-anchored metalloproteinase regulator RECK stabilizes focal adhesions and anteriorposterior polarity in fibroblasts. Oncogene 28, 1454-1464 (2009).
5. Muraguchi T, Takegami Y, Ohtsuka T, Kitajima S, Chandana EP, Omura A, Miki T, Takahashi R,
Matsumoto N, Ludwig A, Noda M, Takahashi C. RECK modulates Notch signaling during cortical
neurogenesis by regulating ADAM10 activity. Nat Neurosci 10, 838-845 (2007).
- Basic Medicine (Core Departments) - Medical Genetics
Molecular Genetics
Our long-term goal is to use spermatogonial stem cells for genetic modification. We have recently succeeded in long-term culture
of mouse spermatogonial stem cells. Due to their unique morphology, we named them germline stem (GS) cells. GS cells have
several advantages over ES cells. First, although ES cells are only available during the embryonic period, GS cells can be derived
from postnatal animals. Second, they are not tumorigenic and committed to the germline lineage. Given that ES cells with
germline potential have been obtained only from mice, our GS cell technology may resolve current challenges with ES cells and
greatly contribute to the development of new transgenic technologies. We are now trying 1) to modify the genome of GS cells
and 2) to derive GS cells from other animal species.
Takashi Shinohara, M. D., Ph. D.,
Professor
❶
●
Spermatogonial stem cells are the only stem cells
in the body that can transmit genetic information to
the offspring. Current methods to create transgenic
animals are based on oocytes or eggs. Although
germline can be efficiently modified in mice, it is
inefficient or impossible in other animal species.
Our long-term goal is to use spermatogonial stem
cells for genetic modification. In 1994, a technique
to transfer spermatogonial stem cells was developed.
Testis cells transferred into the seminiferous tubules
of infertile animals form colonies of spermatogenesis ❶ Growth of GS cells in vitro
❷ Growth of mGS cells in vitro
and produce donor-derived offspring by mating with
❸ people in the lab
females. Using this technique, we have developed
several new methods to manipulate spermatogonial
●
❸
stem cells. It is now possible to 1) purify stem cells,
2) introduce retrovirus into stem cells for transgenic
animal production, and 3) treat male infertility by
gene therapy. However, due to the lack of culture
technique, genetic modification of stem cells was not
efficient.
We have recently succeeded in long-term culture
of mouse spermatogonial stem cells. Due to their
unique morphology, we named them germline stem
(GS) cells. GS cells have different morphology
from embryonic stem (ES) cells, and can grow
exponentially in vitro for more than 2 years. Upon
transplantation into infertile animals, GS cells can
produce normal fertile offspring, indicating that they
are real stem cells. GS cells have several advantages
over ES cells. First, although ES cells are only
available during the embryonic period, GS cells can
be derived from postnatal animals. Second, they
are not tumorigenic and committed to the germline
lineage. Given that ES cells with germline potential
have been obtained only from mice, our GS cell
technology may resolve current challenges with ES
cells and greatly contribute to the development of
new transgenic technologies. We are now trying 1) to
modify the genome of GS cells and 2) to derive GS
cells from other animal species.
❷
●
Recent Publications
Molecular Genetics
Professor : Takashi Shinohara
Assistant
Professor : Mito Kanatsu-Shinohara,
Seiji Takashima, Satoshi Tanaka
TEL
: +81-75-751-4160
FAX
: +81-75-751-4169
e-mail
: [email protected]
1. Kanatsu-Shinohara, M. et al. (2003) Long-term proliferation in culture and germline transmission
of mouse male germline stem cells. Biol. Reprod. 69, 612-616.
2. Kanatsu-Shinohara, M. et al. (2004) Generation of pluripotent stem cells from neonatal mouse
testis. Cell 119, 1001-1012.
3. Kanatsu-Shinohara, M. et al. (2006) Production of knockout mice by random and targeted
mutagenesis in spermatogonial stem cells. Proc. Natl. Acad. Sci. USA 103, 8018-8023.
4. Kanatsu-Shinohara, M. et al.(2008) Homing of mouse spermatogonial stem cells to germline niche
depends on beta1-integrin. Cell Stem Cell 3, 533-542.
5. Lee, J.et al. (2009) Genetic reconstruction of mouse spermatogonial stem cell self-renewal in vitro
by Ras-cyclin D2 activation. Cell Stem Cell 5, 76-86.
- Basic Medicine (Core Departments) - Medical Genetics
Radiation Genetics
The Department of Radiation Genetics was founded for the purpose of basic research and education in the field of Radiation
Biology in 1961. Dr. Shunichi Takeda took over a departmental Head in 1998, and has studied molecular mechanism of
radiotherapy and chemotherapy of tumors by employing a reverse genetic approach using a chicken B lymphocyte line and
Medaka fish as model system. Our unique and efficient system allows students to publish their data in qualified journals while
quickly learning essence of genetics and experimental techniques.
Shunichi Takeda, M.D., Ph.D.
Professor
Forward and Reverse genetics is a method for the functional
analysis of various proteins. Forward genetics aims to identify
mutants with particular malfunctions, that are subsequently
used to identify the gene responsible for the observed
phenotype. The approach of reverse genetics starts at the
opposite end with a gene, whose function needs to be analyzed.
Gene disruption by gene targeting technologies in cells or
animals, and phenotype analysis of the resulting mutants is a
powerful way to learn about the molecular role of genes. We
have developed Reverse genetic research systems using the
chicken B lymphocyte line DT40, and recently the Medaka
fish. We are using these systems to understand the function of
a variety of genes in DNA repair, recombination, replication,
cell cycle, and its checkpoint regulation. A defect in these
processes often leads to tumor genesis. The understanding of the
molecular details of these defects is thus useful for development
of tailor-made therapy. Moreover, reverse genetic approaches
will be used more and more in clinical applications, with the
development of efficient gene disruption techniques by siRNA
and viral gene therapies.
Among cells of higher eukaryotes, DT40 is an ideal model
system for reverse genetic studies, because the frequency of gene
targeting is increased by two orders of magnitude when compared
to mammalian cells. Another advantage is the very stable
phenotype of these cells that make it easy to compare different
mutants to wild type cells. Using DT40 cells, Ph.D. students
can learn all basic molecular and cellular biology techniques in
projects involving gene disruption and phenotype analysis, as
shown in Figure 1 as an example. Moreover, our students are
publishing their results in high-qualified journals. Hence, most
first authors in our labs publications are Ph.D. students.
Medaka (Figure 2) as well as Zebra-fish as genetic model
systems have several advantages over rodents in medical
studies. Using this system one can quickly perform a large
number of genetic experiments, such as genetic crosses,
creation of transgenic fishes, injection of anti-strand RNA
into fertilized eggs to specifically suppress any given
genes, and storage of mutant lines by making frozen sperm
aliquots. Medaka and zebra-fish are complementary to each
other because studies of each species have advantages and
disadvantages when compared to each other. Our lab was the
first to create gene disrupted Medaka fishes in 2005. This
break-through will certainly make our medical school the
center of excellence in the medical research of Medaka in the
world. Making gene disrupted Medaka lines from scratch in
any research field of your interest, you will be able to become
a pioneer just like the first settlers in America 200 years ago.
Once you found a way in this unique system, you will feel no
reason to stick to the rodent experimental system, where there
are too many old die-hard experts similar to the aristocrats in
18th century Europe.
Reverse genetics in these unique experimental systems is highly
educative particularly for beginner students. Avoiding fierce
competition as in studies on mice and human materials, you
will be able to learn effectively from your colleagues because
everybody in our laboratory shares the same experimental
methods and materials while studying different genes. You can
study both systems and publish data in three years to defend
your thesis. Seminars are done in English twice a week. We
will also support a few months externship in top laboratories in
Europe or America during the Ph.D. course.
Radiation Genetics
Professor : Shunichi Takeda
Associate
Professor : Kouji Hirota
Assistant
Professor : Akira Motegi
TEL
: +81-75-753-4410
FAX
: +81-75-753-4419
e-mail
: [email protected]
URL
: http://rg4.rg.med.kyoto-u.ac.jp/
Kyoto University
❶
●
❶ Ph.D. students can learn all techniques necessary for performing the following
experiment within three years. To visualize dynamics of chromosomes during mitosis,
Green fluorescent protein (GFP) gene was knocked-in towards the endogenous locus
of a kinetochore protein gene, CENP-H in the chicken B lymphocyte line DT40. This
GFP tagged CENP-H substituted for loss of wild-type CENP-H protein, indicating that
the chimeric protein works normally. Using this newly developed phenotypic assay, we
evaluated the role of Scc1 protein by conditional inactivating Scc1, whose homolog is
known to be essential for mitotic cell division in yeast. From this result, we conclude
that Scc1 promotes association of the spindle body with mitotic chromosomes thereby
contributing to accurate transmission of chromosomes to daughter cells.
Recent Publications
1. Iijima J, Zeng Z, Takeda S, Taniguchi Y. (2010) RAP80 acts independently of BRCA1 in repair of
topoisomerase II poison-induced DNA damage. Cancer Res. (in press)
2. Hirota K, Sonoda E, Kawamoto T, Motegi A, Masutani C, Hanaoka F, Szuts D, Iwai S, Sale JE,
Lehmann A, Takeda S. (2010) Simultaneous disruption of two DNA polymerases, Pol η(eta)and
Pol ζ(zeta), in avian DT40 cells unmasks the role of Pol η(eta) in cellular response to various DNA
lesions. PLoS Genet. (in press)
3. Kohzaki M, Nishihara K, Hirota K, Sonoda E, Yoshimura M, Ekino S, Butler JE, Watanabe M,
Halazonetis T, Takeda S. (2010) DNA polymerases ν(nu) and θ(theta) are required for efficient
Immunoglobulin V gene diversification in chicken. J Cell Biol. 189: 1117-1127.
4. Nakamura K (graduate school student), Kogame T, Takeda S, Taniguchi Y, et al. (9), (2009)
Collaborative action of Brca1 and CtIP in elimination of covalent modifications from double-strand
breaks to facilitate subsequent break repair. PLoS Genet. (in press)
5. Zhao GY (graduate school student), Takeda S, et al. (10), (2007) A critical role for the ubiquitinconjugating enzyme Ubc13 in initiating homologous recombination. Mol Cell. 25: 663-675.
6. (Review) Kinoshita M, Takeda S. (2007) Connecting the Dots between Septins and the DNA
Damage Checkpoint. Cell 130: 777-9.
- Basic Medicine (Core Departments) - Basic Neuroscience
The primary focus of our research has been on the neuronal circuitry and synaptic organization of the mammalian brain, and
the ultimate goal is to elucidate the neuronal design and mechanism that produces the ‘mind’. To this end, various pathways
in the brain and spinal cord are analysed morphologically with light and electron microscopes by means of tracer techniques,
immunocytochemistry, in situ hybridization histochemistry, and intracellular recording/staining method. Recently, the efforts
are strongly focused on (1) the development and application of the molecular-biological tools for completely visualizing the
neuronal processes, such as the viral vectors and gene-modified animals. (2) By using the molecular-biological tools which
enable us to visualize information input sites (dendrites and cell body), we are studying the local circuit of the cerebral cortex
and striatum. (3) Further, using the viral vectors that can visualize axon fibers very effectively, we are also examining the whole
axonal arborization of single neurons in the thalamus and basal ganglia.
Takeshi Kaneko, M.D., Ph.D.
Professor
(1) Development of molecular-biological tools for
the morphological study of the brain: We are now
trying to develop many genetic tools for the analysis
of neuronal circuit. The viral vectors expressing
plasma membrane-targeted GFP has been developed
to visualize neurons in a Golgi-stain-like manner.
Furthermore, graduate students are producing
genetically altered animals that express dendritic
membrane-targeted GFP selectively in a particular
subset of neurons. (2) Study of local circuitry in the
cerebral cortex and striatum: Local neuronal circuitry
is considered to be the basis of the higher functions
executed by the brain. A graduate student is studying
the cortical local connection of a pyramidal neuron
to the corticothalamic neuron group, combining the
intracellular staining technique with the retrograde
dendrite-labeling method of the viral vector. Another
graduate student is examining the local connection
of a cortical interneuron to the corticospinal
projection neuron group, using the whole cell
recording/labeling technique in the genetically
modified animals in which cortical interneurons are
labeled with GFP. Furthermore, after generation
of transgenic animals in which the dendrites of a
particular set of cortical and striatal interneurons
are labeled in a Golgi-stain-like fashion, we are
now analyzing excitatory and inhibitory inputs to
the particular set of interneurons on electron and
confocal laser-scanning fluorescent microscopes. (3)
Single neuron labeling study of thalamic and basal
ganglia neurons: Using the viral vector that produces
the plasma membrane-targeted GFP, we have
recently reported the complete axonal arborization
of thalamocortical and nigral dopaminergic neurons
at the single neuron level. Graduate students and
postdoctoral fellows are now examining other
thalamocortical and thalamostriatal neurons in many
thalamic subnuclei, and also studying projection
neurons in the basal ganglia nuclei, such as the Recent Publications
striatum, globus pallidus, subthalamic nucleus and 1. Tanaka T, Kaneko T, Aoyagi T, Recurrent infomax generates cell assemblies, neuronal avalanches,
and simple cell-like selectivity. Neural Computation 21:1038-67, 2009 .
substantia nigra.
Professor : Takeshi Kaneko
Associate
Professor : Fumino Fujiyama
Assistant
Professor : Takahiro Furuta, Hiroyuki Hioki
TEL
: +81-75-753-4331
FAX
: +81-75-753-4340
e-mail
: [email protected]
URL
: http://www.mbs.med.kyoto-u.ac.jp/
2. Kuramoto E, Furuta T, Nakamura KC, Unzai T, Hioki H, Kaneko T. Two types of thalamocortical
projections from the motor thalamic nuclei of the rat: A single neuron tracing study using viral
vectors. Cerebral Cortex 19: 2065-77, 2009 .
3. Matsuda W, Furuta T, Nakamura KC, Hioki H, Fujiyama F, Arai R, Kaneko T. Single nigrostriatal
dopaminergic neurons form widely spread and highly dense axonal arborizations in the
neostriatum. The Journal of Neuroscience, 29: 444-53, 2009.
4. Furuta T, Kaneko T, Deschênes M. Septal neurons in barrel cortex derive their receptive field input
from the lemniscal pathway. The Journal of Neuroscience 29: 4089-95, 2009.
5. Ohira K, Furuta T, Hioki H, Nakamura KC, Kuramoto E, Tanaka Y, Funatsu N, Shimizu K, Oishi
T, Hayashi M, Miyakawa T, Kaneko T, Nakamura S. Ischemia-induced neurogenesis of neocortical
layer 1 progenitor cells. Nature Neuroscience, 13: 173-9, 2010.
6. Furuta T, Urbain N, Kaneko T, Deschênes M. Corticofugal control of vibrissa-sensitive neurons in
the interpolaris nucleus of the trigeminal complex. The Journal of Neuroscience 30: 1832-38, 2010.
In recent years, progress in various methods of research has opened the doors to revealing much about the integrative functions
of the brain, such as emotion, consciousness, and the mind. However, there is still much to be learned about the brain. The brain
is an organ, acquired in the course of evolution, for information processing, and it is a highly sophisticated system made up of
over 100 billion intertwined neurons. It can do the work that not even the most advanced computer could possibly carry out.
The study of the brain is not complete unless approached from both the biological (the hardware) and the computational (the
software) angles. People proficient in all sorts of disciplines are invited to collaborate in exploring this ultimate theme.
Kenji Kawano, M.D., Ph.D.
Professor
Various techniques employed in neuroscience, such
as molecular biology, neuroanatomy, and brain
imaging techniques are constantly unfolding and
reporting new findings. It is a rapidly advancing
field. In our laboratory, we address the brain as
an information processing system, and apply
neurophysiological techniques to study the function
of the intricate neural network that is behind human
perception, planned action and thought. (1) We focus
on visual tracking responses of the eyes to study
the transformation of sensory to motor information.
We have recorded neuronal activities in different
parts of the brain while monkeys performed visualoculomotor tasks. We analyzed the data using
mathematical methods and revealed the role of
the cerebral cortical area MST and cerebellum in
controlling the ocular following response. To fully
understand the function of the brain, we have found
that simultaneously application of two approaches
most effective. One is the analytical approach
based on the biological properties of the neurons
by electrophysiology, and the other is an integrative
high level systems approach by computational
neuroscience. We will continue to pursue this theme
in studying higher brain functions. (2) The aim of
another group is to elucidate neural mechanisms
underlying visual attention. We examined neuronal
activities in multiple cortical areas of macaque
monkeys performing a visual search, and have
revealed the hierarchical and integrative processing
manner over multiple cortical areas.
Education and training of young prospective
researchers are also our primary concern. We have a
comprehensive series of lectures for graduate school
(master course) students and neuroscience seminars
for graduate school (doctor course) students.
❶ Information processing
in the brain for ocular
following response.
❷ Multidimensional visual
search task and neuronal
dynamics of bottom-up
and top-down signals in
visual area V4
❸ A set-up for a human
oculomotor experiment.
❹ Staffs
❶
●
❷
●
❸
●
❹
●
Recent Publications
Professor : Kenji Kawano
Associate
Professor : Tadashi Ogawa
Assistant
Professor : Takeshi Nishio, Kenichiro Miura
TEL
: +81-75-753-4675
FAX
: +81-75-753-4486
e-mail
: [email protected]
URL
: http://www.brain.med.kyoto-u.ac.jp/
Kyoto University
1. Inaba N, Miura K, Kawano K (2011) Direction and speed tuning to visual motion in cortical areas
MT and MSTd during smooth pursuit eye movements. J Neurophysiol. (in press).
2. Ogawa T, Komatsu H, (2010) Differential temporal storage capacity in the baseline activity of
neurons in macaque frontal eye field and area V4. J Neurophysiol. 103: 2433-45.
3. Miura K, Kobayashi Y, Kawano K. (2009) Ocular responses to brief motion of textured
backgrounds during smooth pursuit in humans. J Neurophysiol. 102:1736-47.
4. Ogawa T, Komatsu H. (2009) Condition-dependent and condition-independent target selection in
the macaque posterior parietal cortex. J Neurophysiol. 101:721-36.
5. Miura K, Sugita Y, Matsuura K, Inaba N, Kawano K, Miles FA (2008) The initial disparity
vergence elicited with single and dual grating stimuli in monkeys: evidence for disparity energy
sensing and nonlinear interactions. J Neurophysiol. 100:2907-18.
Physiology and Neurobiology (Physiology 1)
Auditory system has many marvelous capabilities. It can discriminate small difference of sound frequency, and it can identify the
location of sound source in high precision. Although our nervous system is operating by using a clock of approximately 1 msec,
our auditory system can detect a time difference of 10 μ(micro)sec or less. We are studying these capabilities of our nervous
system for hearing, trying to understand the mechanisms how to calculate the interaural difference of time and intensity of sound,
and then how to create the space map of hearing around us within the brain.
Harunori Ohmori, M.D., Ph.D.
Professor
❶
●
Barn owl can catch the prey in darkness, guided
completely by hearing. Because of its preciseness on
sound source localization, Barn owl is told to have
a super sense of hearing. When the sound source
moved in 1 degree in the azimuth plane, a small
difference of sound travel time was created between
two ears. It would be about 4 μ(micro)sec in the owl,
and 2 μ(micro)sec in the chicken, and 10 μ(micro)
sec in man; these differences are dependent on the
size of head. Man and owl can detect this small
difference of time. From the investigation how the
❷
●
accuracy of coincidence detection is achieved on
the chicken nervous system for hearing, we found
that the precise calculation of time difference was
made by the fast synaptic interaction between sound
signals originating in the left and the right ears. We
can now predict some optimal condition in which
even chicken could calculate the sound source
localization as precisely as owl. In these studies to
explore the neural mechanisms of hearing, we utilize
various techniques of electrophysiology, morphology ❶ Projection and terminal morphology
of auditor y ner ve fibers in the Ncl.
and molecular biology depending on the purpose of
Magnocelluaris (NM) of chicken, a part
experiment.
of cochlear nucleus in birds. Shapes of
nerve terminals are specialized in the
graded manner, and are large calyx
form in the high and small bouton form
in the low frequency region. Neurons
in NM extract the timing information of
sound through this synapse formed by
the auditory fiber, and then transmit it
bilaterally to Ncl. Laminaris (NL).
❷ Neurons in NL receive temporal
infor mation of sound from bilateral
NM and calculate the time difference
between them. The shape of neuron is
characteristic; extending many dendrites
in two poles, and one axon emerges from
the cell body (inset). These neurons are
arranged in one layer in NL and work as
precise coincidence detectors.
Recent Publications
Physiology and Neurobiology (Physiology 1)
Professor : Harunori Ohmori
Associate
Professor : Hiroshi Kuba
Assistant
Professor : Rei Yamada, Iwao Fukui
TEL
: +81-75-753-4351
FAX
: +81-75-753-4349
e-mail
: [email protected]
URL
: http://www.nbiol.med.kyoto-u.ac.jp
1. Fukui I, Sato T and Ohmori H (2006). Improvement of phase information at low sound frequency
in nucleus magnocellularis of the chicken. Journal of Neurophysiology 96:642-651.
2. Kuba,H Ishii, MT and Ohmori,H (2006). Axonal site of spike initiation enhances auditory
coincidence detection. Nature 444:1069-1072.
3. Ishii, MT Nakashima, N and Ohmori,H (2007). Tytophan-scanning mutagenesis in the S1 domain
of mammalian HCN channel reveals residues critical for voltage-gated activation. Journal of
Physiology Mar 1; 579 (pt2):291-301, 2007.
4. Nishino, Eri Yamada,R Kuba,H Hioki,H Furuta,T Kaneko,T and Ohmori, H (2008). SoundIntensity-Dependent Compensation for the Small Interaural Time Difference Cue for Sound Source
Localization. Journal of Neuroscience 28(28): 7153-7164.
5. Kuba, H and Ohmori,H (2009) Roles of axonal sodium channels in precise auditory time coding at
nucleus magnocellularis of the chick. Journal of Physiology Jan 15: 587(Pt1): 87-100.
- Basic Medicine (Core Departments) - Basic Neusocience
Cell Pharmacology
The concept of pharmacology is being revolutionalized from classical discipline of description of drug actions to examining
functions of biological molecules for effective drug invention. Our group is pursuing such a brand-new style of pharmacological
approach while focusing on functions of prostaglandin receptors and Rho small G proteins. Such an approach requires
integration of multi-level understanding from the molecular and cellular levels to the whole-system. We most welcome young
enthusiastic people interested in physiology and medicine join our group regardless of their educational backgrounds.
Shuh Narumiya, M.D., Ph.D.
Professor
Our goal is to understand physiological and
pathological roles of prostaglandin receptors and
Rho small G proteins not only at the molecular and
cellular levels but also at the whole-system level.
Collaborating with pharmaceutical companies, we
also aim to develop drugs specifically targeting
these molecules and their related signaling pathways
for their potential clinical application. More
specifically, in the field of prostaglandin receptors,
while advancing our understanding of their actions
in inflammation, immunity, fever and pain by
using mice deficient with prostaglandin receptors,
we are revealing their unexpected functions such
as behavioral control under psychological and
social stress. We are also paving the way for the
clinical application of drugs acting on prostaglandin
receptors for allergy. In the field of Rho small G
proteins, we are challenging the central questions
of cell biology including mechanisms for cell
attachment, migration as well as cytokinesis. By
generating mice deficient with Rho effectors, we are
studying the system-level functions of Rho small G
proteins such as those in structural formation and
plasticity of the central nervous system. Y compound,
a specific ROCK inhibitor we developed, is also
considered for its potential clinical use. Therefore our
laboratories are realizing a novel pharmacological
approach integrating understandings at the molecular
and cellular levels to those at the whole-system level.
We are also interested in developing researchers with
multidisciplinary scope of physiology and medicine,
which are required for system-level science in the
postgenome era.
Cell Pharmacology
Professor : Shuh Narumiya
Associate
Professor : Toshimasa Ishizaki,
Takako Hirata (AK Project)
Assistant
Professor : Tomoyuki Furuyashiki, Daiji Sakata
TEL
: +81-75-753-4392
FAX
: +81-75-753-4693
e-mail
: [email protected]
URL
: http://www5.mfour.med.kyoto-u.ac.jp
Kyoto University
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❷
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❶ Eight members of the
prostanoid receptor
family and structure of the
thromboxane receptor.
❷ Actin stress fibers in
Swiss 3T3 fibroblasts and
cytokinesis of HeLa cells.
❸ Lab personnels
Recent Publications
1. Watanabe, S. et al. (2010) Rho and anillin-dependent control of mDia2 localization and function in
cytokinesis. Mol. Biol. Cell, 21, 3193-3204.
2. Esaki, Y. et al. (2010) Dual roles of PGE2-EP4 signaling in mouse experimental autoimmune
encephalomyelitis. Proc. Natl. Acad. Sci. U. S. A., 107, 12233-12238.
3. Tanaka, Y. et al. (2009) Prostaglandin E receptor EP1 enhances GABA-mediated inhibition of
dopaminergic neurons in the substantia nigra pars compacta and regulates dopamine level in the
dorsal striatum. Eur. J. Neurosci., 30, 2338-2346.
4. Oga, T. et al. (2009) Prostaglandin F2alpha receptor signaling facilitates bleomycin-induced
pulmonary fibrosis independently of transforming growth factor-beta. Nat. Med., 15, 1426-1430.
5. Yao, C. et al. (2009) Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1
cell differentiation and Th17 cell expansion. Nat. Med., 15, 633-640.
- Basic Medicine (Core Departments) - Preventive Medicine
Public Health
The increases of lifestyle-related diseases, avian influenza and other infectious diseases, safety problems of the food including
mad cow disease and so forth have occurred not only on a large scale in Japan but on a worldwide scale. As well in public health
research, we study these problems from various viewpoints, and are carrying out research works about measures and solutions.
In particular, we have worked with councils, municipalities and public health centers to discuss these public health problems and
proposed measures to them. Moreover, about the measures against smoking which is a global problem, we have discussed about
them in several countries. For this reason, having knowledge of medicine and /or the public health system in Japan are required
for our researchers,as well as the ability of speaking English.
Toshitaka Nakahara, M.D., Ph.D.,M.P.H
Professor
Our department, whose basis is public health
department of the medical school, deals with
public health in the Faculty of Medicine and public
health and international health in the School of
Public Health. In education, we carry out in several
programs, such as the public health in the faculty of
medicine and public health, public health and welfare
administration and health care administration in the
School of Health Science. We also deal with corecurriculum, health policy and international health in
the School of Public Health.
We use the qualitative and quantitative analysis
method and its fusion-technique, and the socialmarketing-technique in research, focusing on health
education for lifestyle-related diseases (hypertension,
diabetes mellitus, hyperlipidemia, osteoporosis )
,and measures against smoking, and HIV/AIDS.
We analyze present condition, and are developing
more effective and more efficient methods for them.
Since in the field of public health, not only study but
also practice is necessary, we cooperate with some
councils, municipalities and prefectures to solve
public health problems and we apply the results
of our studies progressively. The measures against
smoking which is one of the main causes of lifestylerelated diseases, not only in Japan but all over the
world, has made them the main targets of our studies.
We also held and national and international meetings(
62nd Annual meeting of Japanese Public Health
Society, 2nd General Meeting of IUHPE-NPWP.
1st meeting of the Japanese Association of Smoking
Control Science and, in 2008 7th annual meeting of
International Society for the Prevention of Tobacco
Induced Diseases).
Now, besides studies on health education of
lifestyle related diseases, we also carry out studies
on the safety of foods,including measures against
terrorism,research on public health and law, and
sanitation, not only in Japan but overseas as well.
Public Health
Professor : Toshitaka Nakahara
Associate
Professor : Kazunari Satomura
Assistant
Professor : Suketaka Iwanaga
TEL
: +81-75-753-4465
FAX
: +81-75-753-4466
e-mail
: [email protected]
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❶ The 7th Annual Meeting of International Society for the Prevention of Tobacco Induced
Diseases
❷ After The 19th Japanese Society of Health Education and Promotion
Recent Publications
1. Current Japanese Tobbacco Consumption Situation. Toshitaka Nakahara, K. Satomura, S.
Iwanaga, R. Sakamoto, M. Noami, T. Takahashi Tobacco Counters Health, Volume 4, ISBN 817211-208-4, P.11-13 2005
2. Hospital's Measures against Passive Smoking. Ryota Sakamoto, Toshitaka Nakahara, Kazunari
Satomura, Suketaka Iwanaga, Megumi Noami, Akihiko Kinugasa Tobacco Counters Health,
Volume 4, ISBN 81-7211-208-4, P.23-27 2005
3. What is Necessary to Obey the FCTC in Japan. Kazunari Satomura, Toshitaka Nakahara, Suketaka
Iwanaga, Ryota Sakamoto, Megumi Noami, Toru Takahashi Tobacco Counters Health, Volume 4,
ISBN 81-7211-208-4, P.32-35 2005
4. Changes of Health Warning Labellings on Japanese Tobacco Packages Suketaka Iwanaga,
Toshitaka Nakahara, Kazunari Satomura, Ryota Sakamoto, Megumi Nomai, Toru Takahashi
Tobacco Counters Health, Volume 4, ISBN 81-7211-208-4, P.36-38 2005
5. New approaches to public health education, research and practice Toshitaka Nakahara Raku-Yu 10
4-5 2006
6. Takashi Muto, Toshitaka Nakahara, Eun Woo Nam : Asian Perspectives and Evidence on Health
Promotion and Education. Springer 2011
- Basic Medicine (Core Departments) - Institute of Laboratory Animals
A high-quality draft sequence of the rat genome was reported in March, 2004. Considering the importance of the laboratory rat
in medical research, our main research is focused on this species. Since fiscal year 2002, our institute ILA has been a core center
for the rat of the National Bio Resource Project in Japan, and contributes to the promotion of biomedical science. We welcome
postgraduate students who are interested in our project.
Tadao Serikawa, D.V.M., Ph.D.
Professor
The laboratory rat (Rattus norvegicus) is very useful
to study prevention and treatment of human diseases,
because of its suitable body size for manipulation
and its physiology that is very similar to that of
humans. Our research focus is the identification of
causative genes of these rat models by means of
genetic analysis. This approach can discover novel
genes which are related to human diseases. We,
now, intensively try to identify causative genes of
the Noda Epileptic Rat (NER) which shows toniccolonic seizures. Another research focus is to
establish rat models of human diseases by “reversegenetic” approaches. Recently, new technologies
were established to create genetically-modified
rats by ENU mutagenesis, zinc-finger nuclease, ES
cells, and iPS cells. We have already developed rat
modes of colon cancer, febrile seizure, epilepsy,
and immune-deficiency. Our efforts aim to develop
excellent rat models of human diseases and, by using
these rat models, we intend to find pathological
mechanisms of diseases and develop new methods to
prevent and treat human diseases.
The National Bio Resource Project - Rat grows
to one of the largest resource center in the world
and globally distributes high-quality rat strains to
interested researchers.
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❶ Lab Staff
❷ X-SCID rats generated
by zinc-finger nuclease
technology (left-upper :
thymic deficiency, rightlower: xenotransplantation
of human ovarian cancer
cells)
❸ National Bio Resource
Project - Rat
Recent Publications
Institute of Laboratory Animals
(Laboratory Animal Science)
Professor : Tadao Serikawa
Associate
Professor : Takashi Kuramoto, Tomoji Mashimo
Senior
Lecturer : Taketo Kaneko
TEL
: +81-75-753-4489
FAX
: +81-75-753-4409
e-mail
: [email protected]
URL
: http://www.anim.med.kyoto-u.ac.jp/
Kyoto University
1. A mutation in the gene encoding mitochondrial Mg2+ channel MRS2 results in demyelination in
the rat.Kuramoto T, Kuwamura M, Tokuda S, Izawa T, Nakane Y, Kitada K, Akao M, Guénet JL,
Serikawa T. PLoS Genet. 7(1):e1001262, 2011
2. A missense mutation of the gene encoding voltage-dependent sodium channel (Nav1.1) confers
susceptibility to febrile seizures in rats.Mashimo T, Ohmori I, Ouchida M, Ohno Y, Tsurumi T,
Miki T, Wakamori M, Ishihara S, Yoshida T, Takizawa A, Kato M, Hirabayashi M, Sasa M, Mori Y,
Serikawa T. J Neurosci, 30(16):5744-53, 2010
3. Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using
zinc-finger nucleases. Mashimo T, Takizawa A, Voigt B, Yoshimi K, Hiai H, Kuramoto T, Serikawa
T. PLoS One. 5(1):e8870, 2010
4. The STAR Consortium*, Saar K, Beck A, Bihoreau MT, Birney E, Brocklebank D, Chen Y,
Cuppen E, Demonchy S, Dopazo J, Flicek P, Foglio M, Fujiyama A, Gut IG, Gauguier D, Guigo
R, Guryev V, Heinig M, Hummel O, Jahn N, Klages S, Kren V, Kube M, Kuhl H, Kuramoto T,
Kuroki Y, Lechner D, Lee YA, Lopez-Bigas N, Lathrop GM, Mashimo T, Medina I, Mott R, Patone
G, Perrier-Cornet JA, Platzer M, Pravenec M, Reinhardt R, Sakaki Y, Schilhabel M, Schulz H,
Serikawa T, Shikhagaie M, Tatsumoto S, Taudien S, Toyoda A, Voigt B, Zelenika D, Zimdahl H,
Hubner N. SNP and haplotype mapping for genetic analysis in the rat. Nat Genet. 40(5):560-566,
2008
5. Aitman TJ, Critser JK, Cuppen E, Dominiczak A, Fernandez-Suarez XM, Flint J, Gauguier D,
Geurts AM, Gould M, Harris PC, Holmdahl R, Hubner N, Izsvák Z, Jacob HJ, Kuramoto T, Kwitek
AE, Marrone A, Mashimo T, Moreno C, Mullins J, Mullins L, Olsson T, Pravenec M, Riley L, Saar
K, Serikawa T, Shull JD, Szpirer C, Twigger SN, Voigt B, Worley K. Progress and prospects in rat
genetics: a community view. Nat Genet. 40(5):516-522, 2008
6. Mashimo T, Yanagihara K, Tokuda S, Voigt B, Takizawa A, Nakajima R, Kato M, Hirabayashi M,
Kuramoto T, Serikawa T. An ENU-induced mutant archive for gene targeting in rats. Nat Genet.
40(5):514-515, 2008
- Basic Medicine (Core Departments) - Congenital Anomaly Research Center
Congenital Anomaly Research Center
Approximately 3% of newborn babies suffer from congenital anomalies (birth defects), which is a serious burden for patients
and their families. Many congenital anomalies are assumed to be caused by the interaction of gene mutations and environmental
factors, but the etiology and pathogenetic mechanisms remain to be clarified for most birth defects. In our laboratory,
interdisciplinary research approaches are being undertaken to elucidate the causes and pathogenesis of birth defects and to
attempt to identify some preventive measures.
Keiji Tamaki, M.D.,
Director and Professor
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This Center has the largest collection of human embryo
specimens in the world comprising of over 44,000 therapeutic
abortuses. Most of the specimens are between the 3rd and 8th
week following fertilization, which is the critical period of
teratogenesis. In the Kyoto Collection of Human Embryos,
an appreciable number of malformed embryos are included,
which provide a unique opportunity to study the early stages of
abnormal morphogenesis. A variety of research projects are at
present being undertaken on the embryo collection.
1) Pathological and molecular cell biology analyses of human
malformations
Among the early embryo population, many malformations
have been demonstrated to be present several times more
frequently than in the newborn population. We are in the process
of investigating the early pathogenetic process of various
malformations, such as neural tube defects, holoprosencephaly
and oral clefts. Where possible, the genes of abnormal embryos
are analyzed by molecular methods.
2) 3D database of human prenatal development
Using the magnetic resonance (MR) microscope, a 3D
database of normal and abnormal human embryos is in the
process of being established (http://bird.cac.med.kyoto-u.
ac.jp). This database will be useful not only in the study of
human embryology but also for future gene mapping studies
in human development. This is a collaborative research with
Prof. Katsumi Kose of Tsukuba University and has been funded
by the "Bioinformatics R & D (BIRD)" Project of the Japan
Science and Technology Agency (2005-2010).
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3) Genetic epidemiological study of the etiology of human birth
defects
Genetic epidemiological studies can be undertaken more
efficiently in the embryo population than in newborns, since the
prevalence rates of various malformations are much higher in
embryos. To date, we have identified the association between
neural tube defects and maternal hyperthermia and also clarified
that more than 90% of embryos with serious malformations are
spontaneously aborted early in the gestation period.
4) Experimental studies of abnormal morphogenesis
The pathogenetic mechanisms and preventive measure of
birth defects are being investigated using in vivo and in vitro
experimental systems.
5) Normal development of human embryos
We have identified some important facts about human
morphogenesis, which have corrected some established theories
of development. These include the following: (a) neural tube
closure in human embryos is initiated at multiple sites; and
(b) apoptosis or “programmed cell death” is not a necessary
prerequisite for palate fusion.
6) Development of a multimedia tutorial program for human
embryology
Using the human embryo data, we are developing a novel
tutorial program of human embryology with the aid of
computer graphics and other multimedia technologies. This is
a collaboration with the Academic Center for Computing and
Media Studies of Kyoto University.
Congenital Anomaly Research Center
Professor : Keiji Tamaki
Associate
Professor : Shigehito Yamada
TEL
: +81-75-753-4345
FAX
: +81-75-753-4621
URL
: http://www.cac.med.kyoto-u.ac.jp/
❶ An 8-week human embryo in the amniotic sac
❷ Computer graphic images of human embryonic development between the 4th and 8th
weeks following fertilization
❸ A 7-week embryo and the 3D reconstructed image of its brain
❹ MR images of 6-, 7- and 8-week embryos
❺ Sectional MR images of a 7-week embryo
❻ Histology lab with serial histological sections of 1,000 embryo cases
Recent Publications
1. Yamada S, Lee ES, Samtani RR, Lockett E, Uwabe C, Shiota K, Anderson SA, Lo CW.
Developmental atlas of the early first trimester human embryo. Dev Dyn, 2010 Jun;239(6):158595.
2. Ayman A, Funatomi T, Mihon M, Elnomery Z, Okada T, Togashi K, Sakai T, Yamada S. New
region growing segmentation technique for MR images with weak boundaries. IEICE Technical
Report 2010 Nov;110:71-76.
3. Bleyl SB, Saijoh Y, Bax NA, Gittenberger-de Groot AC, Wisse LJ, Chapman SC, Hunter
J, Shiratori H, Hamada H, Yamada S, Shiota K, Klewer SE, Leppert MF, Schoenwolf GC.
Dysregulation of the PDGFRA gene causes inflow tract anomalies including TAPVR: integrating
evidence from human genetics and model organisms. Hum Mol Genet. 2010 Apr 1;19(7):1286-301.
Epub 2010 Jan 13.
4. Shiota K, Yamada S. Early pathogenesis of holoprosencephaly. Am J Med Genet C Semin Med
Genet, 2010 Jan;154(1):22-28.
5. Dhanantwari P, Lee E, Krishnan A, Samtani R, Yamada S, Anderson S, Lockett E, Donofrio
M, Shiota K, Leatherbury L, Lo CW. Human cardiac development in the first trimester: a
high-resolution magnetic resonance imaging and episcopic fluorescence image capture atlas.
Circulation. 2009 Jul 28;120(4):343-51.
- Basic Medicine (Core Departments) - Genome Epidemiology
Center for Genomic Medicine
Study of human diseases based on genetic information in the human genome is one of the most important subjects in the
Post Genome Project. In particular, to overcome human multigenetic disorders, it is essential to perform trans-ethnic genetic
analyses of human genome variations. In our laboratory, we perform SNP identification and genotyping of candidate genes
of multigenetic diseases using DNA samples of patients and control subjects from different ethnic origins. We also work on
the construction of a comprehensive SNP database of different multigenetic diseases which integrates genetic and clinical
information using the latest bioinformatic and statistical genetic tools. We try to establish a new generation genome variationbased genomic strategy which will directly linked to clinical research and therapeutics.
Fumihiko Matsuda, Ph.D.
Professor
We have established an extensive international
collaboration for ‘Genomic Epidemiology of Human
Multigenetic Disorders’ with Centre National de
Genotypage (CNG) in France. We focus on diseases
related to the immune system such as Rheumatoid
Arthritis, Lupus, Hyperthyroidism and AIDS, and
those in which DNA repair mechanism is involved
such as cancer. We have started a systematic SNP
identification using a standard panel of DNA
samples from multiple ethnic groups (Caucasians,
Japanese, Africans, Thai). Based on the SNP catalog
obtained, we undertake a large-scale case/control
study by genotyping SNPs on an epidemiological
scale (sample scale of >1,000 individuals). Results
are deposited in a disease-based genetic database
which contains information of genes and their
genetic variations combined with patient’s clinical
information. Extensive statistical analyses is
performed using a variety of statistical programs
developed from joint research with CNG and The
Rockefeller University in U.S.A. Comparison of
genotypes between patients and controls among
different ethnicities leads to the identification of
disease-specific and ethnicity-specific genome
variations. Annotated data will be made available to
the scientific community as basic genetic information
of diseases for future development of diagnostics and
individual-based therapy (taylor-made medicine).
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❶ Laboratry
members
Recent Publications
Professor : Fumihiko Matsuda
Associate
Professor : Hiroshi Kadotani
Associate Professor
(Industry-Academia Collaboration)
: Yoshiki Murakami
Assistant
Professor : Meiko Takahashi
TEL
: +81-75-753-4661
FAX
: +81-75-753-9314
e-mail
: [email protected]
URL
: http://www.genome.med.kyoto-u.ac.jp/
Kyoto University
1. SEARCH Collaborative Group, Link, E., Parish, S., Armitage, J., Bowman, L., Heath, S., Matsuda,
F., Gut, I., Lathrop, M. and Collins, R. (2008) SLCO1B1 variants and statin-induced myopathy--a
genomewide study. N. Engl. J. Med. 359, 789-799.
2. McKay, J.D. et al. (2008) Lung cancer susceptibility locus at 5p15.33. Nat. Genet. 40, 1404-1406
3. Wada, M., Marusawa, H., Yamada, R., Nasu, A., Osaki, Y., Kudo, M., Nabeshima, M., Fukuda, Y.,
Chiba, T. and Matsuda, F. (2009) Association of genetic polymorphisms with interferon-induced
haematologic adverse effects in chronic hepatitis C patients. J. Viral. Hepat. 16, 388-396.
4. Nakanishi, H., Yamada, R., Gotoh, N., Hayashi, H., Yamashiro, K., Shimada, N., Ohno-Matsui, K.,
Mochizuki, M., Saito, M., Iida, T., Matsuo, K., Tajima, K., Yoshimura, N. and *Matsuda, F. (2009)
A Genome-Wide Association Analysis Identified a Novel Susceptible Locus for Pathological
Myopia at 11q24.1. PLoS Genetics Epub 2009 Sep 25.
5. Takahashi, M., Saenko, V. A., Rogounovitch T. I., Kawaguchi, T., Drozd, V. M., TakigawaImamura, H., Natallia M. Akulevich, N. M., Ratanajaraya, C., Mitsutake, N., Takamura, N.,
Danilova, L. I., Lushchik, M. L., Demidchik, Y. E., Heath, S., Yamada, R., Lathrop, M., Matsuda,
F. and Yamashita, S. (2010) The FOXE1 locus is a major genetic determinant for radiation-related
thyroid carcinoma in Chernobyl. Hum. Mol. Genet. Mar 30. [Epub ahead of print]
6. Nalpas, B., Lavialle-Meziani, R., Plancoulaine, S., Jouanguy, E., Nalpas, A., Munteanu, M.,
Charlotte, F., Ranque, B., Patin, E., Heath, S., Fontaine, H., Vallet-Pichard, A., Pontoire, D.,
Bourlière, M., Casanova, J. L., Lathrop, M., Bréchot, C., Poynard, T., Matsuda, F., Pol, S. and Abel,
L. (2010) Interferon-γ receptor 2 gene variants are associated with liver fibrosis in patients with
chronic hepatitis C infection. Gut. In the press
- Basic Medicine (Core Departments) - Center for Genomic Medicine
Genome Informatics
More than 20,000 genes are there in the human genome. Comparing to the annotation of genes, how their expression is regulated
are largely unknown. Moreover, identification of these regulatory regions in the genome seems to be very important for
molecular medicine because mutations in these regions might be responsible for many diseases. Our goal is to understand the
mechanisms of gene regulation in genomic scale by bioinformatics approaches.
Mikita Suyama Ph.D
Associate Professor
Today, more than 40 genomic sequences of
various vertebrates are available, and comparative
genome analyses is necessary to understand the
changes in genomic structures and to identify
functional regions. The main focus of our group
is to get most insights into the regulation of gene
expression, which may cause some diseases, by using
bioinformatics means. The current research topics
are (1) identification of cis-regulatory elements for
transcription and splicing, (2) comparative genome
analyses to understand gene duplications and genome
rearrangements, (3) genome informatic analysis of
sex differences, and (4) gene expression in cancer
tissues. With the progress of high-throughput
analyses, such as microarrays and next-generation
sequence technologies, interpretation of the data is
not possible without computational analyses. We will
incorporate such heterogeneous data together with
the sequence data into the genome-wide functional
analyses.
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❶ A genome sequence alignment and
a cis-element conserved among
mammals.
❷ Microarray analysis of differentially
expressed genes in inflammatory
colitis.
Massive data analysis is not only for
bioinformaticians, but the researchers working at the
bench are also required to master to use some basic
tools and databases. To support those researchers,
we provide them with the bioinformatics expertise
necessary for the genome sequence analyses and the
high-throughput data analyses.
An interactive process between experimental
molecular biologists and bioinformaticians is
necessary to fully facilitate genome data and highthroughput data. Such process includes feedbackloop between hypothesis making and experimental
verification. Therefore, we will also actively
collaborate with others to get much further insights
into molecular medicine.
Recent Publications
Genome Informatics
Associate
Professor : Mikita Suyama
Assistant
Professor : Tetsuya Sato
TEL
: +81-75-753-4383
FAX
: +81-75-753-4382
e-mail
: [email protected]
1. Suyama M, Harrington ED, Vinokourova S, von Knebel Doeberitz M, Ohara O, and Bork P, A
network of conserved co-occurring motifs for the regulation of alternative splicing, Nucleic Acids
Res. 38:7916-7926, 2010.
2. Iizuka Y, Okuno T, Saeki K, Uozaki H, Okada S, Misaka T, Sato T, Toh H, Fukayama M, Takeda
N, Kita Y, Shimizu T, Nakamura M, and Yokomizo T, Protective role of the leukotriene B4 receptor
BLT2 in murine inflammatory colitis, FASEB J. 24:4678-4690, 2010.
3. Soldà G, Suyama M, Pelucchi P, Boi S, Guffanti A, Rizzi E, Bork P, Tenchini ML, and Ciccarelli
FD, Non-random retention of protein-coding overlapping genes in Metazoa, BMC Genomics
9:174, 2008.
4. Suyama M, Harrington E, Bork P, and Torrents D, Identification and analysis of genes and
pseudogenes within duplicated regions in the human and mouse genomes, PLoS Comput. Biol.
2:e76, 2006.
5. Suyama M, Torrents D, and Bork P, PAL2NAL: robust conversion of protein sequence alignments
into the corresponding codon alignments, Nucleic Acids Res. 34:W609-W612, 2006.
- Basic Medicine (Core Departments) - Center for Medical Education
Medical Education
Center for Medical Education
Topics concerning medical education have currently become important issues for our community.
The traditional style of medical education has mainly been carried out through the efforts of individual departments of a medical
school. Nowadays, however, it is impossible to provide an appropriate medical education without coordination of the efforts of
individual sections. Therefore, the Center for Medical Education has been established at Kyoto University to play a central role
in the promotion of modern medical education.
The Center for Medical Education at Kyoto
University is not one of the departments in the
medical school. It has been established to promote
medical education across the faculty, rather than to
facilitate specific research or education carried out by
individual departments.
Center is continuing the revision of medical
education system of Kyoto University. Particularly
recent activity has been focused to the reform of the
framework of undergraduate clinical training course.
With cooperation of many hospitals the course
has been reformed as a clerkship-based pathway.
Making e-learning systems we are now establishing
the e-campus among all teachers and students.
Improvement of postgraduate education is also one
of missions of this center. We cooperate with the
Education Center of Kyoto University Hospital in
promoting resident education. For example faculty
development of mentors for residents is one of main
tasks for our center. We also support carrier planning
of residents and students.
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❶ Core Members
❷ Center for Medical
Education located
in the building D
In addition to improving the system of medical
education, the center is also engaged in development
of learning program, such as a new basic course in
Medical English, and a practical resuscitation clinical
program for treatment of sudden cardiac arrest
patients.
Medical Education
(Center for Medical Education)
Senior
Lecturer : Takeshi Morimoto,
(Yuko Maeda: Human Health Science
Research Fields )
Assistant
Professor : Mio Sakuma
School Affairs
Staff
: Susumu Seki
Assistant Teaching
Staff
: Kaori Takada
secretary
: Makiko Ohtorii, Ai Mizutani,
Mika Sakai
Office
Assistant : Izumi Miki
TEL
: +81-75-753-9338
FAX
: +81-75-753-9339
e-mail
: [email protected]
URL
: http://plaza.umin.ac.jp/~cme/
Kyoto University
Recent Publications
1. Hamasu S, Morimoto T, Kuramoto N, Horiguchi M, Iwami T, Nishiyama C, Takada K, Kubota
Y, Seki S, Maeda Y, Sakai Y, Hiraide A. Effects of BLS training on factors associated with attitude
toward CPR in college students. Resuscitation 2009;80:359-364.
2. Kuramoto N, Morimoto T, Kubota Y, Maeda Y, Seki S, Takada K, Hiraide A. Public perception and
willingness to perform bystander CPR in Japan. Resuscitation 2008;79:475-481
3. Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, Jinnouchi H, Sugiyama S,
Saito Y; Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
Investigators. Low-dose aspirin for primary prevention of atherosclerotic events in patients with
type 2 diabetes: a randomized controlled trial. JAMA. 2008;300:2134-41.
- Basic Medicine (Core Departments) - Immunology and Genomic Medicine
Contributed Chairs
We have been studying molecular mechanisms controlling development and function of lymphocytes. Currently we are
addressing two important questions: 1) How antibody diversity is controlled by AID, a putative RNA-editing enzyme required
for class switch recombination (CSR) and somatic hypermutation (SHM), 2) How PD-1 deficiency leads to development of
autoimmune diseases.
Tasuku Honjo, M.D., Ph.D.
Professor
“The mechanism of antibody memory”
The use of vaccination to prevent infectious diseases has
made profound and enduring impacts on human welfare
since it was pioneered by Jenner in 1796. Extensive studies
on immunoglobulin structure and function established
that effective vaccination depends on the generation of
antigen-specific antibody ‘memory’ characterized by
two modifications of the immunoglobulin, namely class
switching in the heavy-chain constant region, and an
increased affinity for antigen in the variable region.
In 1978, we proposed and subsequently proved that
class switch is mediated by recombination with dynamic
excision of genomic fragments. In 2000, we discovered
activation-induced cytidine deaminase (AID), which is
responsible for DNA cleavage to initiate both CSR and
SHM. Surprisingly, AID mutates not only the antibody
gene, but also protooncogenes. Whether or not AID induced
in non-lymphoid cells by viral infection causes genomic
alterations leading to cancer is a big question in the field.
We have recently found that topoisomerase 1 (Top1) is the
enzyme that initiates CSR and SHM by cleaving S and V
region, respectively. In addition, AID reduces the amount
of Top1, inducing the target DNA structural change, which
causes the irreversible cleavage by Top1. Furthermore, the
transcription coupled nucleosomal reassembly is critical for
this Top1-mediated DNA cleavage during CSR and SHM.
Furthermore, we also investigate the function of
Programmed cell-death-1 (PD-1), which was isolated in this
laboratory and shown to be the key molecule in regulation
of lymphocyte activity including tolerance. PD-1 plays
critical roles in anti-cancer immunity and autoimmunity.
The aim of our research is to contribute to human welfare
through regulation of immune responses, elucidation of
tumorigenesis and its prevention by studying the function
of AID and PD-1. In our lab, highly motivated students
and postdocs are collaboratively working to elucidate
fundamental questions in immunology. We educate them
to be independent and sophisticated scientists who are
not only specialized in biochemical and immunological
experimental techniques, but also have global view of life
science.
Professor : Tasuku Honjo
Associate
Professor : Nasim Begum, Maki Kobayashi
Assistant
Professor : Shunsuke Chikuma
TEL
: +81-75-753-4371
FAX
: +81-75-753-4388
e-mail
: [email protected]
URL
: http://www2.mfour.med.
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❶Class Switch
Recombination
research group
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❷AID engraves
antibody memory on
the genome
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❸ PD-1 research group
❹ PD-1 deficient mice
develop autoimmune
neuropathy due
to the breakage
of lymphocyte
tolerance
Recent Publications
1. Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y. and Honjo, T. “Class switch
recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential
RNA editing enzyme.” Cell (2000) 102(5):553-63.
2. Muramatsu, M., Nagaoka, H., Shinkura, R., Begum, N. A. and Honjo, T. “Discovery of activationinduced cytidine deaminase, the engraver of antibody memory.” Adv. Immunol. (2007) 94:1-36.
3. Kobayashi, M., Aida, M., Nagaoka, H., Begum, N. A., Kitawaki, Y., Nakata, M., Stanlie, A., Doi,
T., Kato, L., Okazaki, I., Shinkura R., Muramatsu, M., Kinoshita, K. and Honjo, T. “AID-induced
decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch
recombination.” Proc. Natl. Acad. Sci. USA (2009) 106:22375-80.
4. Stanlie, A., Aida, M., Muramatsu, M., Honjo, T. and Begum, N. A. “Histone3 lysine4
trimethylation regulated by the facilitates chromatin transcription complex is critical for DNA
cleavage in class switch recombination.” Proc. Natl. Acad. Sci. USA (2010) 107: 22190-5.
5. Wei, M., Shinkura, R., Doi, Y., Maruya, M., Fagarasan, S. and Honjo, T. “Knock-in mice carrying a
somatic hypermutation-defective Aicda mutation have impaired gut homeostasis and compromised
mucosal defense.” Nat. Immunol. (2011) 12: 264-70.
- Basic Medicine (Core Departments) - Center for Genomic Medicine
Diversity is a fundamental feature of biology. Recent developments in genomics and related research fields with massive
data have provided great opportunities to investigate biological diversity. The concept of health and diseases is an aspect of
phenotypic heterogeneity itself, which means medical approach to the diversity is important. Statistical genetics is the study
to understand biological diversity by expressing the diversity by combining genetic and environmental components with
mathematical methods. Although it has a long and sound history since Gregor Johann Mendel, there are few laboratories titled
“statistical genetics” in Japan. This laboratory in graduate school of medicine, Kyoto University, has just started in August,
2009. Another feature of statistical genetics is that it is becoming more and more interdisciplinary encompassing mathematics,
statistics, information science, computer science, genetics, molecular biology and medicine and therefore you can start statistical
genetics from any one of these basic fields.
Our study goals are development of new datamining methods for genetic polymorphisms and also
assistance of data-mining processes of collaborators.
We mainly target medically important phenotypes
such as diseases and we are also interested in the
heterogeneity in human phenotypes itself. Our
laboratory does not perform biological experiments
and when we analyze real data, they are provided
by collaborators. We consider collaborations with
data-producing laboratories very important. The
structure of genetic polymorphisms is characterized
by its very high dimension and small number of
discrete categories of individual dimension, two
or four. We believe it would be useful to utilize
these features in development of new data-mining
methods, although it is not mandatory. It would be a
good idea to apply some data-mining strategies, that
are in use or are being studied in other data-mining
research fields, into our research field. It would also
be important to attempt to apply more basic theories
or technologies into our data-mining that are not
conventionally used in other data-mining fields
either. In case where basic theories or technologies
are applied to our field, the above-mentioned features
of data structure of polymorphisms would give
good insights in the studies. Statistical genetics is
interdisciplinary covering mathematics, statistics,
information science, computer science, genetics,
molecular biology and medicine. We will support
anybody to use resources inside and/or outside
of Kyoto University to master the details of these
related fields.
❶
●
Yamada, Ryo M.D., Ph.D.
Professor
❹
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❷
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❸
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❺
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❶ Statistical tests in genetic epidemiology requires much lower type-1 error threshold,
which brings a new problem in discrepancy between asymptotic tests and exact tests.
The figure draws the discrepancy in geometric expression.
❷ Neighboring loci make haplotypes, combination types of single alleles. Two dichotomous
loci make four haplotypes, which are placed in three-dimensional space and
chronological changes in haplotype frequency is displayed in the space.
❸ Haplotypes are expressed as strings of 0 and 1. Genetic distance among them can be
defined with number of recombinations required. For this purpose, the concept of runs is
useful.
❹ This figure is two-dimensional drawing of higher-dimensional cubes. Also they are graphs
of lattices, which represent relation among the elements of a power set. It is useful
to handle haplotypes, strings of 0 and 1, with these tools in discrete mathematic for
development of methods of data mining.
❺ A part of an article.
Recent Publications
Professor : Yamada, Ryo M.D., Ph.D.
TEL
: +81-75-753-9470
FAX
: +81-75-753-9284
e-mail
: [email protected].
ac.jp
URL
: http://www.genome.med.kyoto-u.ac.jp/
wiki_tokyo/index.php
Kyoto University
1. Yamada R, Okada Y. An optimal dose-effect mode trend test for SNP genotype tables. Genet
Epidemiol. 2009 33(2):114-27
2. Suzuki A, Yamada R, Kochi Y, Sawada T, Okada Y, Matsuda K, et al. Functional SNPs in
CD244 increase the risk of rheumatoid arthritis in a Japanese population. Nat Genet. 2008
Oct;40(10):1224-9.
3. Yamamoto K, Yamada R. Lessons from a Genomewide Association Study of Rheumatoid Arthritis.
N Engl J Med. 2007 September 20, 2007;357(12):1250-1.
4. Yamada R, Matsuda F. A novel method to express SNP-based genetic heterogeneity, Psi, and its use
to measure linkage disequilibrium for multiple SNPs, D(g), and to estimate absolute maximum of
haplotype frequency. Genet Epidemiol. 2007 Nov;31(7):709-26.
5. Cha PC, Yamada R, Sekine A, Nakamura Y, Koh CL. Inference from the relationships between
linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related
genes in four Asian populations. J Hum Genet. 2004;49(10):558-72.
- Clinical Medicine (Core Departments) - Internal Medicine
Hematology is one of the areas in which active interactions and mutual stimulations between clinical medicine and basic science
have been producing remarkable progress. We are trying to obtain deeper insights into mechanisms of and develop effective
treatments for various hematological diseases, with a motto, “from bedside to bench, from bench to bedside”.
Akifumi Takaori
Professor
For cure of hematological malignancies and
infectious diseases, we are engaged in several
research projects of both basic and clinical
approaches. Ongoing clinical research projects
are as follows: 1. functional analysis of dendritic
cells and its application to the immunotherapy of
hematological malignancies, and 2. cell-mediated
immunotherapy for hematological malignancies
including adult T-cell leukemia using hematopietic
stem cell transplantation. Basic approaches to
hematological and infectious diseases include:
1. functional analysis of phagocytes and other
cells involved in the innate and acquired immune
systems, 2. analysis of the function and expression
of molecules related to iron metabolism, 3. research
on the tumorigenesis and pathology of various
hematological malignancies including malignant
lymphoma, adult T-cell leukemia and MDS/MPD,
and 4. elucidation of the mechanisms by which
HIV-1 Vif and an antiviral host factor, APOBEC3G,
regulate the infectivity of HIV-1. Motivations for
these basic research projects have also been arisen
during our daily clinical work. We are making efforts
to keep pace with rapid advances in hematology, and
wish to contribute much to its further progress.
❶
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❶ Immunohistochemical detection of PD-1
ligands in Hodgkin/Reed-Sternberg cells.
(A) H&E, (B) CD30, (C) B7-H1, (D) B7-DC.
❷ Vif induces G2 cell cycle arrest in the
presence of p53.
❸ Bortezomib inhibits trafficking of TLR9,
but not of Unc93b, from the ER to
endolysosomes induced by CpG ODN.
(A, B) TLR9: green, lysosome: red. (C, D)
Unc93B: green, lysosome: red.
Recent Publications
Professor : Akifumi Takaori
Associate
Professor : Norimitsu Kadowaki
Senior
Lecturer : Hiroshi Kawabata, Kouhei Yamashita,
Assistant
Professor : Tadakazu Kondo, Momoko Nishikori,
Masayuki Kobayashi,
Masakatsu Hishizawa,
Toshio Kitawaki, Keisuke Shindo
TEL
: +81-75-751-3150
FAX
: +81-75-751-3201
e-mail
: [email protected]
URL
~hemonc/
1. Hirai, M., Kadowaki, N., Kitawaki, T., Fujita, H., Takaori-Kondo, A., Fukui, R., Miyake, K.,
Maeda, T., Kamihira, S., Miyachi, Y. & Uchiyama, T. (2011). Bortezomib suppresses function and
survival of plasmacytoid dendritic cells by targeting intracellular trafficking of Toll-like receptors
and endoplasmic reticulum homeostasis. Blood 117, 500-9.
2. Izumi, T., Io, K., Matsui, M., Shirakawa, K., Shinohara, M., Nagai, Y., Kawahara, M., Kobayashi,
M., Kondoh, H., Misawa, N., Koyanagi, Y., Uchiyama, T. & Takaori-Kondo, A. (2010). HIV-1 viral
infectivity factor interacts with TP53 to induce G2 cell cycle arrest and positively regulate viral
replication. Proc Natl Acad Sci U S A 107, 20798-803.
3. Hishizawa, M., Kanda, J., Utsunomiya, A., Taniguchi, S., Eto, T., Moriuchi, Y., Tanosaki, R.,
Kawano, F., Miyazaki, Y., Masuda, M., Nagafuji, K., Hara, M., Takanashi, M., Kai, S., Atsuta, Y.,
Suzuki, R., Kawase, T., Matsuo, K., Nagamura-Inoue, T., Kato, S., Sakamaki, H., Morishima, Y.,
Okamura, J., Ichinohe, T. & Uchiyama, T. (2010). Transplantation of allogeneic hematopoietic stem
cells for adult T-cell leukemia: a nationwide retrospective study. Blood 116, 1369-76.
4. Yamashita, K., Miyoshi, T., Arai, T., Endo, N., Itoh, H., Makino, K., Mizugishi, K., Uchiyama, T.
& Sasada, M. (2008). Ozone production by amino acids contributes to killing of bacteria. Proc Natl
Acad Sci U S A 105, 16912-7.
5. Yamamoto, R., Nishikori, M., Kitawaki, T., Sakai, T., Hishizawa, M., Tashima, M., Kondo,
T., Ohmori, K., Kurata, M., Hayashi, T. & Uchiyama, T. (2008). PD-1-PD-1 ligand interaction
contributes to immunosuppressive microenvironment of Hodgkin lymphoma. Blood 111, 3220-4.
6. Shirakawa, K., Takaori-Kondo, A., Yokoyama, M., Izumi, T., Matsui, M., Io, K., Sato, T., Sato,
H. & Uchiyama, T. (2008). Phosphorylation of APOBEC3G by protein kinase A regulates its
interaction with HIV-1 Vif. Nat Struct Mol Biol 15, 1184-91.
Recent studies demonstrate that not only classical endocrine organs but also virtually every tissue and organ possess the
endocrine function. Based on this new concept of endocrinology and metabolism, we, the members of Department of Medicine
and Clinical Science (Endocrinology and Metabolism) are focusing upon the diseases of endocrinology and metabolism,
especially Metabolic Syndrome, which is so-called “life style-related diseases,” such as obesity, diabetes mellitus, hypertension
and hyperlipidemia, and is the cluster of risk factors for atherosclerosis. We are investigating the pathogenesis of the syndrome
and its complications, and performing translational research for the development of new therapeutic strategies.
Kazuwa Nakao, M.D., Ph.D.
Professor
Department of Medicine and Clinical Science (Endocrinology
and Metabolism) was founded in 1899 and has the history
more than 110 years. Since 1992, under the supervision of
Dr. Kazuwa Nakao, Professor and Chairman, the members
of the department are engaged in the research activity aiming
at the establishment of frontier medicine, in addition to the
investigation on classical endocrine and metabolic diseases.
Our goal is to achieve the elucidation of pathogenesis and the
prevention of “life style-related diseases,” such as obesity,
diabetes mellitus, hypertension, and their complications, and
to develop new therapeutic strategies. In education and clinical
services, our department is devoted to fostering expert doctors
for endocrinology and metabolism and related fields, who can
perform high quality and up-to-date diagnostic procedures
and treatments. Furthermore, based upon the characteristics of
endocrinology and metabolism to approach the maintenance of
internal milieu, we aim at training “Physician Scientist” who
can evaluate the patient as a whole and grasp the whole picture
of pathophysiology the patient exhibits. Recently, as Japanese
life-style is being westernized, Metabolic Syndrome, the cluster
syndrome of obesity, diabetes mellitus, hypertension and
hyperlipidemia, and its complications have been emphasized as
an important social issue. We therefore focus especially upon
this medical field and do comprehensive and advancing medical
practice. In research activities, in order to achieve translational
research which links basic research with clinical applications,
we are performing molecular medical approach with molecular
biology, molecular genetics and developmental biology to
elucidate the pathogenesis and develop new therapeutic
methods in the field. We, actually, have succeeded in achieving
the clinical application of new hormones, natriuretic peptides,
secreted from the cardiovascular organs, which have long been
considered to be the pump or the vessel for circulation, and
leptin, secreted from the adipose tissue, which is believed as
the mere storage tissue for energy. We are also performing the
research project of vascular regeneration medicine for vascular
complications of the life style-related diseases, using human
embryonic stem (ES) cells and iPS cells, as one of the first
research groups in Japan.
Recent Publications
Professor : Kazuwa Nakao
Associate
Professor : Masashi Mukoyama
Senior
Lecturer : Naohisa Tamura, Koichiro Kuwahara
Assistant
Professor : Masakatsu Sone, Naotetsu Kanamoto,
Junji Fujikura, Yasuaki Nakagawa,
Masako Miura, Toru Kusakabe
Associate Professor (Special Appointment)
: Kiyoshi Mori,Toshio nishikimi
Lecturer (Special Appointment)
: Masato Kasahara, Akihiro Yasoda
Assistant Professor (Special Appointment)
: Hideki Yokoi, Licht Miyamoto,
Yuji Yamamoto, Hideyuki Kinoshita
TEL
: +81-75-751-3168
FAX
: +81-75-761-1195
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~med2/
toppage.html
Kyoto University
1. T. Tanaka, H. Masuzaki, S. Yasue, K. Ebihara, T. Shiuchi, T. Ishii, N. Arai, M. Hirata, H.
Yamamoto, T. Hayashi, K. Hosoda, Y. Minokoshi, and K. Nakao. Central melanocortin signaling
restores skeletal muscle AMP-activated protein kinase phosphorylation in mice fed a high-fat diet.
Cell Metab. 5: 395-402, 2007.
2. J. Fujikura, K. Hosoda, H. Iwakura, T. Tomita, M. Noguchi, H. Masuzaki, K. Tanigaki, D. Yabe,
T. Honjo, and K. Nakao. Notch/Rbp-j signaling prevents premature endocrine and ductal cell
differentiation in the pancreas. Cell Metab. 3: 59-65, 2006.
3. A. Yasoda, Y. Komatsu, H. Chusho, T. Miyazawa, A. Ozasa, M. Miura, T. Kurihara, T. Rogi, S.
Tanaka, M. Suda, N. Tamura, Y. Ogawa, and K. Nakao. Overexpression of CNP in chondrocytes
rescues achondroplasia through a MAPK-dependent pathway. Nat. Med. 10: 80-86, 2004.
4. K. Kuwahara, Y. Saito, M. Takano, Y. Arai, S. Yasuno, Y. Nakagawa, N. Takahashi, Y. Adachi, G.
Takemura, M. Horie, Y. Miyamoto, T. Morisaki, S. Kuratomi, A. Noma, H. Fujiwara, Y. Yoshimasa,
H. Kinoshita, R. Kawakami, I. Kishimoto, M. Nakanishi, S. Usami, Y. Saito, M. Harada, and K.
Nakao. NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and
function. EMBO J. 22: 6310-6321, 2003.
5. K. Yamahara, H. Itoh, T. Chun, Y. Ogawa, J. Yamashita, N. Sawada, Y. Fukunaga, M. Sone, T.
Yurugi-Kobayashi, K. Miyashita, H. Tsujimoto, H. Kook, R. Feil, D. L. Garbers, F. Hofmann, and
K. Nakao. Significance and therapeutic potential of natriuretic peptides/cGMP/cGMP-dependent
protein kinase pathway in vascular regeneration. Proc. Natl. Acad. Sci. USA, 100: 3404-3409,
2003.
6. J. Yamashita, H. Itoh, M. Hirashima, M. Ogawa, S. Nishikawa, T. Yurugi, M. Naito, K. Nakao, and
S. Nishikawa. Flkl-positive cells derived from embryonic stem cells serve as vascular progenitors.
Nature 408: 92-96, 2000.
The Cardiovascular Medicine at Kyoto University, aims at elucidating the cause of the cardiovascular disease and therapeutic
measures for it and making their assessment by use of both basic and clinical research approach. We strongly hope that young
doctors become balanced clinicians who weight not only cardiovascular emergency medicine but also the preventive medical
care. We are also training them to be able to send information about our researches to the world. We have resolved to make
significant contributions to the tomorrow’s cardiovascular medicine in Japan.
Takeshi Kimura
Professor
■Basic Research
·We conduct highly original research in the
cardiovascular field using novel strategies of
molecular biology, physiology and molecular
genetics. Both of the clinical and the basic research
are essential for the progress of the cardiovascular
medicine. Therefore, our basic research group keeps
in close contact with clinical research.
·We try to expand the possibilities of ourselves.
Participation of young researchers or those from
different fields provide us more extensive studies. We
welcome new colleagues who are interested in our
research field.
·Our aim is to elucidate the pathophysiology of
cardiovascular diseases and develop novel methods
of diagnosis and therapeutic strategies. In addition,
we perform translational research with wide clinical
application.
■Clinical Research
Members of the Department of Cardiovascular
Medicine at Kyoto University are continuously
contributing to evidence-based health care through
clinical researches and education in the fields of
cardiovascular medicine. Currently, we conduct
over ten clinical studies including five multicenter
randomized controlled trials in collaboration with
major foremost hospitals in Japan. The major targets
of our clinical research include ischemic heart
disease, heart failure, arrhythmia, peripheral artery
disease, aortic disease, hypertension, and cardiac
rehabilitation.
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❹
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❶ A Murine Model of Acute Myocardial
Infarction
❷ Hypertensive Heart Failure in Dahl
Salt-Sensitive Rat
❸ Cardiac Catheterization Laboratory
❹ Biostatics Seminar for Graduate
Students and young doctors
❺ Staff of Department of Cardiovascular
Medicine
In detail, please visit our department’s homepage.
URL: http://kyoto-u-cardio.jp/
Recent Publications
Professor : Takeshi Kimura
Associate
Professor : (Industry-Academia Collaboration)
Eiichiro Nishi
Senior
Lecturer : Noriaki Kume, Tetuo Shioi, Koh Ono
(Hakubi Project)
Associate Professor :
Motoko Yanagida
Assistant
Professor : Yoshiki Yui, Chiharu Kishimoto,
Satoshi Shizuta, Neiko Ozasa,
Takeru Makiyama
(Industry-Academia Collaboration)
Yoshinori Hiraoka, Mikiko Ohno,
Masao Imai
TEL
: +81-75-751-3185
FAX
: +81-75-751-3289
e-mail
: [email protected]
URL
: http://kyoto-u-cardio.jp/
1. Ohno M, Hiraoka Y, Matsuoka T, Tomimoto H, Takao K, Miyakawa T, Oshima N, Kiyonari H,
Kimura T, Kita T, Nishi E. Nardilysin regulates axonal maturation and myelination in the central
and peripheral nervous system. Nat Neurosci. 2009 Dec;12(12):1506-13.
2. Horiguchi M, Inoue T, Ohbayashi T, Hirai M, Noda K, Marmorstein LY, Yabe D, Takagi K, Akama
TO, Kita T, Kimura T, Nakamura T. Fibulin-4 conducts proper elastogenesis via interaction with
cross-linking enzyme lysyl oxidase. Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19029-34.
3. Inuzuka Y, Okuda J, Kawashima T, Kato T, Niizuma S, Tamaki Y, Iwanaga Y, Yoshida Y, Kosugi
R, Watanabe-Maeda K, Machida Y, Tsuji S, Aburatani H, Izumi T, Kita T, Shioi T. Suppression of
phosphoinositide 3-kinase prevents cardiac aging in mice.Circulation. 2009 Oct 27;120(17):1695-703.
4. Kimura T, Morimoto T, Nakagawa Y, Tamura T, Kadota K, Yasumoto H, Nishikawa H, Hiasa Y,
Muramatsu T, Meguro T, Inoue N, Honda H, Hayashi Y, Miyazaki S, Oshima S, Honda T, Shiode N,
Namura M, Sone T, Nobuyoshi M, Kita T, Mitsudo K; j-Cypher Registry Investigators. Antiplatelet
therapy and stent thrombosis after sirolimus-eluting stent implantation. Circulation. 2009 Feb
24;119(7):987-95. Epub 2009 Feb 9.
5. Kimura T, Morimoto T, Furukawa Y, Nakagawa Y, Shizuta S, Ehara N, Taniguchi R, Doi T,
Nishiyama K, Ozasa N, Saito N, Hoshino K, Mitsuoka H, Abe M, Toma M, Tamura T, Haruna Y,
Imai Y, Teramukai S, Fukushima M, Kita T.Long-term outcomes of coronary-artery bypass graft
surgery versus percutaneous coronary intervention for multivessel coronary artery disease in the
bare-metal stent era. Circulation. 2008 Sep 30;118(14 Suppl):S199-209.
6. Nishiyama K, Horiguchi M, Shizuta S, Doi T, Ehara N, Tanuguchi R, Haruna Y, Nakagawa Y,
Furukawa Y, Fukushima M, Kita T, Kimura T. Temporal pattern of strokes after on-pump and offpump coronary artery bypass graft surgery.Ann Thorac Surg. 2009 Jun;87(6):1839-44.
7. Ozasa N, Furukawa Y, Morimoto T, Tadamura E, Kita T, Kimura T. Relation among Left
Ventricular Mass, Insulin Resistance, and Hemodynamic Parameters in Type 2 Diabetes.
Hypertension Research 2008; 31: 425-432.
Gastroenterology and Hepatology
Our department has been established in 1996 as the first Department of Gastroenterology and Hepatology in all the national
university in Japan. At that time, because our staff members and graduate students got together from various places in and
outside of Kyoto university, the present members consist of a wide variety of people, whose carrier and medical school vary. As a
clinical department, our goal is to produce many good clinical specialists for gastroenterology, who can understand both clinical
medicine and basic science, and to create new modalities for treatment of various gastroenterological diseases.
Tsutomu Chiba, M.D., Ph.D.
Professor
Periods of internship and residency are very
important for young doctors to become good
physicians. So, we are doing our best to educate
young doctors to become general internists as well as
good gastroenterologists. In particular, after finishing
internship and residency, we prepare a special
course for training clinical gastroenterology together
with many affiliated hospitals. Similar to clinical
works, our research projects cover liver diseases,
pancreatico-biliary diseases, and upper and lower
gastrointestinal tract diseases. Particularly, we are
focusing on cancers, immunological diseases such
as inflammatory bowel disease, and regeneration of
gastrointestinal organs. Now, in order to enhance our
ability of accomplishing research, we are sending
young fellows to several distinguished research
laboratories of basic medical science. In addition,
there are quite a few young investigators, who
are now doing research work in abroad. For these
13 years after establishment, we have clarified
significance of occult infection of HBV in the
development of liver cancer, roles of immunological
responses to H. pylori in the development of
various gastric diseases such as gastric cancer and
MALT lymphoma, and have developed a novel
method for treatment of IBD. Moreover, we made
significant contribution to establishing the concept
of autoimmune pancreatitis, and methods for
treating post-operative biliary stricture after livingrelated liver transplantation. From now, we are
going to establish treatment methods for various
gastrointestinal cancers and IBD, and to develop
method for regeneration of liver, that can substitute
liver transplantation.
Gastroenterology and Hepatology
Professor : Tsutomu Chiba
Associate
Professor : Manabu Muto, Norihiko Watanabe,
Tomohiro Watanabe
Senior
Lecturer : Hiroshi Nakase, Naoshi Nishida,
Hiroshi Seno, Hiroyuki Marusawa,
Yoshihide Ueda
Assistant
Professor : Shinichi Miyamoto, Yasumasa Ezoe,
Takahiro Horimatsu, Hiroshi Ida,
Hideyuki Komekado, Shuko Morita,
Yuzo Kodama, Yuko Matsumoto,
Minoru Matsuura
TEL
: +81-75-751-4319
FAX
: +81-75-751-4303
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~gastro/
gastro.html
Kyoto University
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❶ Histology of the gastric mucosa of H. pyloriinfected neonatally thymectomized mice.
Massive infiltration of lymphocytes forming
lymphoid follicles in the body mucosa at 12
months after H. pylori infection in neonatally
thymectomized mice, which resembles
histology of human MALT lymphoma.
❷ While early detection of squamous cell
carcinomas in the head and neck region
and the esophagus have been quite difficult
by conventional white light image (A), NBI
can effectively detect them.
❸ staffs
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Recent Publications
1. Matsumoto Y, Marusawa H, Kinoshita K, Endo Y, Kou T, Morisawa T, Azuma T, Okazaki IM,
Honjo T, Chiba T: Helicobacter pylori infection triggers aberrant expression of activation-induced
cytidine deaminase in gastric epithelium. Nat Med 13:470-476:2007.
2. Ikeda K, Marusawa H, Osaki Y, Nakamura T, Kitajima N, Yamashita Y, Kudo M, Sato T, Chiba
T: Antibody to hepatitis B core antigen and risk for hepatitis C-related hepatocellular carcinoma: a
prospective study. Ann Intern Med 146:649-656:2007.
3. Kido M, Watanabe N, Okazaki T, Akamatsu T, Saga K, Nishio A, Tanaka J, Honjo T, Chiba T :
Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and
PD-1-mediated signaling. Gastroenterology 135:1333-1343:2008.
4. Takai A, Toyoshima T, Uemura M, Kitawaki Y, Marusawa H, Hiai H, Yamada S, Okazaki IM,
Honjo T, Chiba T, Kinoshita K : A novel mouse model of hepatocarcinogenesis triggered by AID
causing deleterious p53 mutations. Oncogene 28:469-478:2009.
5. Matsumoto Y, Marusawa H, Kinoshita K, Niwa Y, Sakai Y, Chiba T : Up-regulation of activationinduced cytidine deaminase causes genetic aberrations at the CDKN2b-CDKN2a in gastric cancer.
Gastroenterology 139:1984-1994:2010
Respiratory diseases have marked variability such as obstructive airway diseases, interstitial lung diseases, lung cancer,
respiratory infection, sleep disorders and respiratory insufficiency. We are energetically engaged in the study of all these
diseases. In the 21st century, the concept “physiome”, which means that the integration of the achievement of molecularcell biology form the view point of organ biology, will be more important. We hope we can create a new world of respiratory
medicine based on “physiome”.
Michiaki Mishima, M.D., Ph.D.
Professor
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Our clinical, educational and research activities are
performed on five categories; obstructive pulmonary
disease, interstitial pulmonary disease, lung cancer,
respiratory infection and sleep disorders / pulmonary
insufficiency.
(1) Obstructive pulmonary disease (bronchial asthma,
COPD)
We study how to control the refractory asthma and cough
variant asthma, and investigate the etiology of COPD.
The type of inflammation of airway in smokers, disease
susceptibility of COPD and the mechanism of airway
remodeling in refractory asthma are also studied.
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(2) Interstitial pneumonia (sarcoidosis, idiopathic
interstitial pneumonia and collagen disease related lung)
The mechanism of the variability of pulmonary fibrosis,
lymphocyte proliferation and regulation of T cell in the
process of fibrosis are investigated.
(3) Lung cancer
The recent prolongation of the life span in patients with the
advanced lung cancer is indebted to the anticancer drugs
of the third generation, and we are now performing multicenter clinical trial to find the best combination of the drugs.
The metastatic factor of the lung cancer and the side effects
of the molecular targeted drugs are also investigated.
(4) Respiratory infection
Genomic analysis and development of vaccines of TB
and atypical mycobacterium and another bacteria are
investigated. The immune system of the host is also studied.
(5) Sleep disorders / pulmonary fibrosis
The optimized protocol of non-invasive positive pressure
ventilation (NIPPV) is investigated toward the patients
with pulmonary insufficiency and sleep disorders such
as obstructive sleep apnea. The effect of NIPPV on the
life span is also studied based on adhesion molecule and
inflammatory cytokine.
Professor : Michiaki Mishima
Associate
Professor : Akio Niimi
Senior
Lecturer : Toyohiro Hirai
Assistant
Professor : Shigeo Muro, Hisako Matsumoto,
Yutaka Ito, Kim Younghhak,
Yuma Hoshino, Isao Ito,
Katsuhiro Masago, Tsuyoshi Oguma,
Daisuke Kinose
TEL
: +81-75-751-3830
FAX
: +81-75-751-4643
e-mail
: [email protected]
URL
: http://www.kukonai.com/
❶ Original CT image and colored image of pulmonary emphysema, where each
emphysema cluster was described in the different colors.:
Fractal analysis using size and number of emphysema clusters offers useful information
about the detection of early emphysema.
❷ Comparison of the airway wall between the different stage of bronchial asthma :
The airway wall thickened as the stage of asthma progressed. CT images can detect the
permanent change of airway wall construction (airway remodeling) in vivo.
Recent Publications
1. Terada K, Muro S, Sato S, et al. Impact of gastro-oesophageal reflux disease symptoms on COPD
exacerbation. Thorax 2008;63:951-5
2. Ueda T, Niimi A, Matsumoto H, Takemura M, et al. TGFB1 promoter polymorphism C-509T and
pathophysiology of asthma. J Allergy Clin Immunol 2008;121:659-64.
3. Masago K, Fujita S, Kim YH,et al. Effect of vascular endothelial growth factor polymorphisms on
survival in advanced-stage non-small-cell lung cancer. Cancer Sci. 2009;100:1917-22.
4. Handa T, Nagai S, Kitaichi M, et al. Long-term complications and prognosis of chronic beryllium
disease. Sarcoidosis Vasc Diffuse Lung Dis 2009;26:24-31.
5. Osawa M, Ito Y, Hirai T, et al. Risk factors for invasive aspergillosis in living donor liver transplant
recipients. Liver Transpl. 2007;13:566-70.
Rheumatology and Clinical Immunology
The Department of Rheumatology and Clinical Immunology is dealing with researches, education and clinical survice of
diseases in which immunological abnormalities are involved in development and pathogenesis, including autoimmune diseases,
connective tissue diseases, rheumatic diseases and allergic diseases. Besides, since the therapeutic application of immunology
covers infection, transplantation and cancer therapy, clinical Immunology will become more important field in terms of its wide
application. We aim to establish the base of clinical immunology and rheumatology in Japan, by elucidating the mechanisms
of autoimmune diseases, developing the new diagnostic and therapeutic strategy, offering the advanced clinical service, and
training the leading researchers and specialists in this field.
Tsuneyo Mimori, M.D., Ph.D.
Professor
❶
●
❷
●
We are now conducting the following studies to examine
etiology and pathogenesis of systemic autoimmune diseases
and to develop new diagnostic and therapeutic strategy for these
diseases.
1) Clinical and pathogenic significance of autoantibodies in
connective tissue diseases:
We discovered many autoantibodies in connective tissue/
rheumatic diseases, identified their target autoantigens,
and elucidated their clinical and pathogenic significance.
We are now developing the assay systems to detect those
autoantibodies (Fig.1).
2) Cloning of novel target antigens for autoantibodies in
rheumatoid arthritis and analysis of their function:
Target autoantigens (calpastatin and follistatin-related protein
(FRP)) recognized by novel autoantibodies in rheumatoid
arthritis (RA) showed inhibitory effects of inflammation. We
have demonstrated that FRP and calpain inhibitor ameliorated
experimental arthritis in mice (Fig.2).
3) Mechanism of autoantibody production and regulation of
autoimmune diseases in lupus model mice:
We aim the immunosuppressive treatments specific for
autoantibody synthesis or autoreactive (pathogenic) Th cell
activation. To develop the new strategy of disease-associated
Th clone-specific immunoregulatory treatments in SLE, we
demonstrated the therapeutic effects of Th cell vaccination on
murine lupus nephritis (Fig.3).
❸
●
❹
●
4) Chemokine, cell adhesion molecule and signal transduction
in cell activation:
Fractalkine is the unique chemokine with chemo-attractive and
adhesive functions, and expressed on inflammatory cytokineactivated endothelial cells. We are investigating the role of
fractalkine in vascular damage. To clarify the pathogenesis of
autoimmune diseases, we are also investigating the function of
lipid rafts in apoptosis and activating signal pathways.
5) Analysis of differentiation mechanism in helper T cells and
gene therapy by immunosuppressive molecules:
We have analyzed the molecular mechanism of helper T cell
differentiation into Th1 and Th2 cells and established a new
model of it including cross-talks among IL-12, Stat4, T-bet and
GATA-3 (Fig.4). Now, we are focusing on the development of
an organ- and/or disease-specific new-generation gene therapy
to autoimmune diseases using antigen-specific CD4 T cells and/
or specific-epitope expressing dendritic cells that are introduced
immune-regulatory molecules by virus vectors.
❶ Detection of autoantibodies
in patients with connective
tissue diseases by RNAimmunoprecipitation assay
❷ A m e l i o r a t i ve e f fe c t o f F P
(follistatin-related protein) in
collagen-mouse arthritis
❸ Ameliorative effect of irradiated
DNA-specific autoreactive T cell
clone against lupus nephritis in
MRL-lpr mouse
❹ Mechanisms of differentiation in
helper T cells
Recent Publications
Rheumatology and Clinical Immunology
Professor : Tsuneyo Mimori
Associate
Professor : Takao Fujii, Takashi Usui
Assistant
Professor : Koichiro Ohmura, Takaki Nojima,
Daisuke Kawabata, Naoichiro Yukawa
TEL
: +81-75-751-4380
FAX
: +81-75-751-4338
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~rheum/
Kyoto University
1. Kawabata D, Tanaka M, Fujii T, Umehara H, Fujita Y, Yoshifuji H, Mimori T, Ozaki S:
Ameliorative effects of follistatin-related protein/TSC-36/FSTL1 on joint inflammation in a mouse
model of arthritis. Arthritis Rheum 50(2):660-668, 2004
2. Tanaka M, Ozaki S, Kawabata D, Kishimura M, Osakada F, Okubo M, Murakami M, Nakao K,
Mimori T: Potential preventive effects of follistatin-related protein/TSC-36 on joint destruction and
antagonistic modulation of its autoantibodies in rheumatoid arthritis. International Immunology
15(1):71-77, 2003
3. Yoneda O, Imai T, Nishimura M, Miyaji M, Mimori T, Okazaki T, Domae N, Fujimoto H, Minami
Y, Kono T, Bloom ET, Umehara H: Membrane-bound form of fractalkine induces IFN-gamma
production by NK cells. Eur J Immunol 33(1):53-58, 2003.
4. Fujii T, Okada M, Mimori T, Craft J: The transmembrane form of TNF-alpha drives autoantibody
production in the absence of CD154: studies using MRL/Mp-Fas(lpr) mice. Clin Exp Immunol
130(2):224-232, 2002
Geriatric Medicine
The Department of Geriatric Medicine, which was founded in 1968, is one of the oldest medical departments with specific
commitment for the medical science and clinical service for the elderly patients in Japan. With the population rapidly ageing
at unprecedented pace, the spectrum of diseases we tackle has been shifted accordingly; patients with cognitive disorders are
increasing in number along with such diseases as cerebrovascular and cardiac disorders, malignant neoplasm and infections.
Considering the comorbidity and chronic course of the diseases of elderly patients and to sustain their physical functions
properly at home, we have implemented several measures including team-based medical care with the support provided by nonmedical as well as medical multidisciplinary professionals. As mentioned below, we also devote ourselves to scientific research
activities such as studies on pathogenesis, prevention and treatment of various diseases common to elderly patients and studies
on cellular senescence.
❶
●
Since its establishment of the department, our
research activities have focused on historically
studies on organ-based medicine such as diabetology,
neurology, gastroenterology, lipidology and
cardiology. Along with these, our current research
activities encompass new approaches in geriatric
medicine, cognitive neurology and a study on
cellular senescence. As to the studies on neurological
disorders of elderly people, we are developing a
method using neuropsychological and imaging
technique to diagnose Alzheimer disease at an early
❷
stage. We also study factors related to the progression ●
of dementia. It is also our important research target
to develop new approach to relieve caregiver burden
and to improve quality of life of dementia patients.
As to the comprehensive geriatric assessment, we are
assessing the ADLs, physical and mental functions of
elderly patients with multidisciplinary professionals
to see which factors are affecting on quality of life
of them. To develop a novel preventive medical
approach, we have established anti-ageing clinic
since 2006. The purpose of the clinic is prevention
and reduction of bed-bound state, based on up-date
❸
information on general ageing. For example, we ●
treat post-menopause women for dislipidemia and
osteoporosis, while we treat elder people as general
clinician. Our educational program includes learning
of history and frontier question in ageing research,
which could be applicable to the future clinical
approach. In our clinical trial, serum oxidative
stress is under examination among patients. We also
scope stress-induced senescence as basic research.
Our keen interest is to disclose the protective effect
of enhanced glycolysis during ageing process.
Lastly, with a sure prediction of an increase of elder
population in global level, we continue to educate
young researchers in the field of gerontology in both
clinical and basic and to train clinical fellows in
Recent Publications
geriatric medicine.
Geriatric Medicine
Senior
Lecturer : Hajime Takechi
Assistant
Professor : Hiroshi Kondoh, Yoshiyuki Hamakawa
TEL
: +81-75-751-3460
FAX
: +81-75-771-9784
e-mail
: [email protected]
URL
: http://www.geriatric.kuhp.kyoto-u.ac.jp/
❶ A snap shot of meeting with
rehab staffs on the progress of
our patients
❷ Concept of anti-aging clinic in
our department
❸ PET imaging of Alzheimer
amyloid
❹ Young and aged cells
❹
●
1. Takechi H, et al. (2010) Scenery Picture Memory Test, a New Type of Quick and Effective
Screening Test to Detect Early Stage Alzheimer Disease Patients. Geriat Gerontol Int 10; 183-190.
2. Artero-Castro A, et al.(2009) Cold-inducible RNA-binding protein bypasses replicative senescence
in primary cells through extracellular signal-regulated kinase 1 and 2 activation. Mol Cell Biol. 29,
1855-68.
3. Dodge H, et al. (2008) Healthy cognitive aging and leisure activities among the oldest old in Japan:
Takashima study. J Gerontol A Biol Sci Med Sci. 63:1193-200.
4. Kondoh H. (2008) Cellular life span and the Warburg effect. Exp Cell Res. 314, 1923-8.
5. Kondoh,H. et al.(2005) Glycolytic enzymes can modulate cellular life span. Cancer Research
65,177-185.
6. Nomura, I,et al, (2005) Inhibition of long term potentiation by amyloid beta is mediated in a
mechanism independent of NMDA receptor or VDCC in hippocampal CA1 pyramidal neurons.
Neurosci. Lett 391,1-6
The department of Diabetes and Clinical Nutrition was founded as the Nutritional Care Unit of Kyoto University Hospital
in 1933, and became the division of Clinical Nutrition in 1981 as a central clinical facility. In 1992, the department was
reestablished to reflect its academic and scientific roles of providing advanced instruction to medical students in the roles of
metabolism and nutrition as well as research opportunities for graduates students in diabetology and nutritional research. We are
very active in research and publication, and we encourage ambitious students to consider joining us.
Nobuya Inagaki, M.D., Ph.D.
Professor
❶
●
Our major interest is to clarify the mechanisms of
the onset of metabolic disease, especially diabetes
mellitus. Our studies include the production and
secretion of insulin in pancreatic Beta-cells (Fig.1),
secretion and action of the incretins such as GIP
and GLP-1 (Fig.2), development of Beta-cell
imaging, pathophysiological and genetic studies of
diabetes mellitus, metabolism in Beta-cell and liver,
transplantation of pancreatic Beta-cells, clinical
study of diabetic mellitus and nutritional disorders,
and development of stimulation system of energy
❷
●
metabolism. For example, we recently have shown
that gastrointestinal polypeptide secreted in the
duodenum plays a critical role in the maintenance
of glycemic homeostasis and succeeded in islet
transplantation from a living donor .
Each research project is independent, and all
graduate students are allowed freedom to pursue
their interest. The teaching staff contributes timely
encouragement, discussion, and advice, and teaches
the practical techniques required to carry out the
experiments. We investigate physiology, pathology,
and molecular and cellular biology using animal ❶ The mechanism of insulin secretion.The figure
indicates the mechanism of insulin secretion from
models and the most advanced analytical methods.
pancreatic beta cells by the stimulation of glucose
During the course of the research, the student learns
or hypoglycemic agents. Several agents use in the
treatment of diabetic patients are the target of our
the numerous skills required for systematic analysis
research.
and scientific decision making.
❷ The roles of incretin in glycemic homeostasis.
Professor : Nobuya Inagaki
Associate
Professor : Shimpei Fujimoto
Senior
Lecturer : Kazuaki Nagashima
Senior Lecturer (Special Appointment)
: Shin-ichi Harashima
Assistant
Professor : Kentaro Toyoda, Akihiro Hamasaki,
Yoshihito Fujita, Norio Harada
: Yasuhiko Nakamura, Masahito Ogura,
Shunsuke Yamane, Yukari Takeda
Kyoto University
❸
●
❹
●
❺
●
Gastric inhibitory polypeptide (GIP) and glucagonlike peptide-1 (GLP-1) are the physiological incretin
that stimulates insulin release upon ingestion of
nutrients. To clarify the roles of these hormones in
the maintenance of glycemic homeostasis, we are
carrying out various experiments using various gene
targeting mice.
❸ The research meeting.Graduate students make a
presentation about their experimental data in English.
❹ The clinical conference is held once a week.We
discuss about the problems in each patient.
❺ The scene on experiment. Each graduate student has
some independent research projects and teachingstuffs advise timely.
Recent Publications
1. Inagaki N. et al. Reconstitution of IATP: an inward rectifier subunit plus the sulfonylurea receptor.
Science. 1995: 270(5239):1166-70
2. Yamada K, Inagaki N. et al. A real-time method of imaging glucose uptake in single, living
mammalian cells. Nat. Protoc. 2007: 2(3)753-62
3. Fujita Y, Inagaki N. Metformin suppresses hepatic gluconeogenesis and lowers fasting blood
glucose levels through reactive nitrogen species in mice. Diabetologia. 2010 Jul;53(7):1472-81.
4. Yoshihara E, Inagaki N, et al. Disruption of TBP-2 ameliorates insulin sensitivity and secretion
without affecting obesity. Nat Commun. 2010 Nov;1(8):127.
5. Mukai E, Inagaki N. et al. Exendin-4 suppresses SRC activation and reactive oxygen species
production in diabetic Goto-Kakizaki rat islets in an Epac-dependent manner. Diabetes. 2011:
60(1):218-26.
6. Nishi Y, Inagaki N. Role of Mitochondrial Phosphate Carrier in Metabolism-Secretion Coupling in
Rat Insulinoma Cell Line INS-1. Biochem J. 2011 in press.
Primary Care & Emergency Medicine
Our department, responsible for the fields of primary care and emergency medicine, was established in April 2006. Our initial
focus and the expectations of people around us were to enhance the quality of emergency medical care and to improve the
education of medical students, residents, and other medical providers. The staff members gathered to achieve these goals come
from different medical schools and have been trained in various specialties. Our department has a positive attitude and a very
free atmosphere. In the future, we would like to contribute to the design of regional medical systems for emergencies and natural
disasters and the education of related health care professionals, while preparing to receive, educate, and train graduate students.
We hope that many people will be interested in working with us at Kyoto University to develop this new field.
Kaoru Koike, MD, PhD.Chairman
Professor
Emergency medicine is the starting point of medical science.
We aim to provide high-quality medical care at any time, 24
hours a day, 365 days per year. Clinically, we are working hard
every day, mainly treating patients who require emergency
services. Our daily motto is “for the patient.” Emergency
medical care requires a multidisciplinary approach, going
beyond the borders of traditional specialties. We thus have a
central role in managing and coordinating the services provided
by the departments in our university hospital and thereby
promptly provide optimal medical care and services to critically
ill patients. We are planning to have our own beds in the future.
【Research and education】
In 2008, we plan to start basic research on conditions such
as serious trauma, sepsis, and burn injuries. Current research
topics include “the development of educational techniques
for emergency medicine and primary care,” “the development
of methods for the dissemination of community-based
cardiopulmonary resuscitation,” “the design of medical systems
for major disasters,” “the design of in-hospital emergency
systems,” “improved emergency medical care before hospital
admission,” and “the design of regional networks for emergency
medical care.” These topics cover diverse fields, ranging
from the response of hospitals to special circumstances to the
establishment of community-based networks and the education
of health care professionals and the general public. Our
department plays a leading role in the development of systems
for cardiopulmonary resuscitation and disaster medicine in
Japan. Although our department was established only a short
time ago, we are now making many presentations at both
international and domestic congresses and serve as members of
the organizational and steering committees of medical societies
involved in emergency medicine. As for education, we are
currently focusing on ways to improve education and training
during the first few years after graduation from medical school.
Major advances have been made in different specialties, and
organ-specific diagnosis and treatment has received increasing
attention. Because we are usually the first department to come
in contact with critically ill patients, our educational and
training programs emphasize the basic processes of diagnosis
and treatment, i.e., potential diagnoses are made on the basis
of patients’ medical history and physical findings; appropriate
examinations are then performed to narrow the diagnosis. To
effectively treat patients in whom emergency procedures are
indicated by their main symptoms and vital signs, our training
programs stress the importance of developing the ability to
perform diagnosis and treatment in parallel. We have actively
introduced off-the-job training, which has recently assumed
increasing importance, and are now developing new training
techniques to further enhance clinical education. We are
planning to also participate in the education of medical students,
as well as the development of training-based medical education
programs.
Primary Care & Emergency Medicine
Professor : Kaoru Koike,M.D.,Ph.D.
Senior
Lecturer : Kakuo Sato, MD.
Kei Nishiyama, MD.
Takao Suzuki, MD.
Assistant
Professor : Shigeru Ohtsuru, MD.
Genta Kato, MD.
Ryosuke Nishio, MD.
TEL
: +81-75-751-4210
FAX
: +81-75-751-4211
e-mail
: [email protected]
URL
: http://kuhp.kyoto-u.ac.jp/~qqigaku/
Recent Publications
1. Nishiyama K, et. al. Chronic obstructive pulmonary disease-An independent risk factor for longterm cardiac and cardiovascular mortality in patients with ischemic heart disease. Int J Cardiol 2010
Aug 20;143(2):178-83.
2. Nishiyama K, et al. Temporal pattern of strokes after on-pump and off-pump coronary artery
bypass graft surgery. Ann Thorac Surg. 87:1839-44, 2009.
3. Hirakawa K, Koike K, et al. Experimental estimation of postmortem interval using multivariate
analysis of proton NMR metabolomic data. Legal Medicine 11: S282-S285,2009
4. Suzuki T, et al. Mitogen activated protein kinase mediates non-genomic pathway of estrogen on T
cell cytokine production following trauma-hemorrhage. Cytokine. 2008;42:32-8.
5. Suzuki T, et al. Estrogen-mediated activation of non-genomic pathway improves macrophages
cytokine production following trauma-hemorrhage. J Cell Physiol. 2008;214:662-72.
Nephrology
The mission of scientists in the Section of Nephrology is to provide the highest level of patient care, and to conduct basic
laboratory and clinical research. Using the latest techniques in biomedical science, molecular biology, immunology, cell biology,
knockout mice and iPS cells, researchers investigate the pathophysiology of kidney disease; function of key molecules; effects
of many medicine; the cause and treatment of interstitial fibrosis; regeneration of kidney; and the development of new and
improved methods to diagnose glomerulosclerosis.
❶
●
Basic research is now mainly focused on tubuloi n t e r s t i t i a l i n j u r y, d i a b e t i c n e p h r o p a t h y, a n d
regeneration of kidney.
i) Novel strategy for the treatment of advanced renal
injuries:
Tubular damage is a final common pathway leading to
end-stage renal disease. Although the administration
of bone morphogenetic protein-7 (BMP-7) has
been shown to repair established tubular injuries its
pathophysiological role remains elusive. We have
recently shown that uterine sensitization-associated
gene-1 (USAG-1), novel BMP antagonist abundantly
expressed in the kidney, is the central negative regulator
of BMP function in the kidney. Inhibition of USAG1 will be promising means of development of novel
treatment for kidney diseases.
ii) Mechanism of the development of diabetic
glomerulosclerosis (collaborative research with
University of Tokushima): Diabetic nephropathy is
characterized by the accumulation of extra-cellular
matrix in glomeruli. To elucidate these mechanisms,
we examine the role of Smad1 for the progression of
diabetic nephropathy, which is the transcriptional factor
we reported to directly regulate the expression of type
IV collagen, the main component of extra-cellular ❶ Disease-specific iPS cells derived from skin cells of a patient with autosomal dominant
polycystic kidney disease (ADPKD)
matrix in sclerotic glomeruli.
iii) Regeneration of kidney:
We also cooperate with the Kidney regeneration group
in CiRA (Kenji Osafune’s lab), focusing on the in
vitro regeneration of kidney from human iPS cells for
transplantation and development of new therapeutic
drugs against renal diseases.
In clinical researches, many studies are going on
by clinical fellows, such as the beneficial effect of
anti-hypertensive drug on renal hemodynamics, the
combined effect of cyclosporin and prednisolone
for minimal change nephrotic syndrome, the iron
metabolism in Japanese hemodialysis patients, and the
role of osteocalcin in CKD-MBD patients. Lastly, to
provide the highest level of patient care, we continue
to educate and train clinical fellows for developing
and acquiring expertise as subspecialists in the field of
clinical nephrology.
Nephrology
Senior
Lecturer : Atsushi Fukatsu
Assistant
Professor : Noriyuki Iehara
Assistant
Professor (Special Apoinntment)
: Takeshi Matsubara
TEL
: +81-75-751-3641
FAX
: +81-75-751-3643
e-mail
: [email protected]
Kyoto University
Recent Publications
1. Osafune K.(2010) *In vitro* regeneration of kidney from pluripotent stem cells. Exp.Cell Res.
316(16): 2571-7.
2. Mima A, et al (2008) Urinary Smad1 is a novel marker to predict later onset of mesangial matrix
expansion in diabetic nephropathy. Diabetes. 57(6): 1712-22.
3. Tanaka M, et al (2008) Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney
development and injury. Kidney Int. 73(2): 181-91.
4. Kanamori H, et al (2007) Inhibition of MCP-1/CCR2 pathway ameliorates the development of
diabetic nephropathy. Biochem Biophys Res Commun. 360(4): 772-7.
5. Sumi E, et al (2007) SRY-related HMG box 9 regulates the expression of Col4a2 through
transactivating its enhancer element in mesangial cells. Am J Pathol. 170(6): 1854-64.
6. Nomura K, et al (2007) Roles of coagulation pathway and factor Xa in rat mesangioproliferative
glomerulonephritis. Lab Invest. 87(2): 150-60.
- Clinical Medicine (Core Departments) - Cutaneous Life Science
Dermatology
Modern dermatology has completely grown out of conservative old dermatology that described only morphology of skin
diseases, thus changing to global cutaneous science which deals with both basic biology and clinical medicine. Our department
gathers many specialists including immunologists, allergologists, photobiologists, molecular biologists and hair biologists who
try to link basic science with clinical dermatology. Especially, immunodermatology and cutaneous regenerative medicine are
two important keywords of our research hopefully leading to fruitful results in dermatology frontier in near future.
Yoshiki Miyachi, M.D., Ph.D.
Professor
❶
●
❷
●
❸
●
In immunodermatology, the biological role of
cultured human mast cells in allergic inflammation
as well as tissue remodeling, and establishment
of human mast cells in animal model using
xenotransplantation of human hematopoietic stem
cells are under investigation, which may provide
valuable tools for investigating allergic skin diseases.
Other hot topics in this field include researches on
molecular mechanism of contact hypersensitivity
using prostaglandin knockout mice, immunological
investigation of dendritic cells and chemokine,
regulatory T cells in autoimmune skin diseases.
❹
●
Neurophyisiological study of itch is another brand
new field of our research.
In cutaneous regenerative medicine, molecular
biological studies of keratinocytes in wound healing,
regeneration of melanocytes as well as hair, cell
biological studies of adhesion molecules, connective
tissue metabolism in aging, and clinical studies of
pressure ulcers are our specialties.
In any event, all basic researches should be evaluated
in view of clinical impact, because we should return
research profits to clinical dermatology contributing
to the improvement of clinical outcomes of patients
with skin diseases. For graduate students, clinical
motivation is absolutely required to start basic
research in cutaneous life science, which in turn may ❶ Nishimura EK, et. al.: Dominant role of the niche in melanocyte stem cell fate
determination. Nature, 416: 854-860, 2002
broaden their capacity and possibility as physician
❷ Kabashima K, et. al.: The prostaglandin receptor EP4 suppresses colitis, mucosal
scientists in future. Our policy in both research
damage and CD4 cell activation in the gut. J Clin Invest, 109:883-893, 2002
and education in graduate school should be greatly ❸ Morita K, et.al.: Molecular architecture of tight junctions of periderm differs from that of
the maculae occludentes of epidermis. J Invest Dermatol, 118:1073-1079, 2002
appreciated by those who want to join us.
❹ Staffs
Recent Publications
Dermatology
Professor : Yoshiki Miyachi
Associate
Professor : Kenji Kabashima
Senior
Lecturer : Yumi Matsumura, Miki Tanioka
Assistant
Professor : Akiko Arakawa, Mayumi Katoh,
Keisuke Egawa, Hideki Tanizaki,
Eri Muroga, Atsusi Otsuka
TEL
: +81-75-751-3310
FAX
: +81-75-761-3002
e-mail
: [email protected]
1. Tomura M, Honda T, Tanizaki H, Otsuka A, Egawa G, Tokura Y, Waldmann H, Hori S, Cyster JG,
Watanabe T, Miyachi Y, Kanagawa O, Kabashima K. Activated regulatory T cells are the major T
cell type emigrating from the skin during a cutaneous immune response in mice.
J Clin Invest. 2010 Mar 1;120(3)653-6
2. Moniaga CS, Egawa G, Kawasaki H, Hara-Chikuma M, Honda T, Tanizaki H, Nakajima S, Otsuka
A, Matsuoka H, Kubo A, Sakabe JI, Tokura Y, Miyachi Y, Amagai M, Kabashima K. Flaky Tail
Mouse Denotes Human Atopic Dermatitis in the Steady State and by Topical Application with
Dermatophagoides pteronyssinus Extract.
Am J Pathol. 2010 May;176(5):2385-93
3. Tanizaki H, Egawa G, Inaba K, Honda T, Nakajima S, Moniaga CS, Otsuka A, Ishizaki T,
Tomura M, Watanabe T, Miyachi Y, Narumiya S, Okada T, Kabashima K. Rho-mDia1 pathway
is required for adhesion, migration, and T-cell stimulation in dendritic cells. Blood. 2010 Dec
23;116(26):5875-84
4. Hirai M, Kadowaki N, Kitawaki T, Fujita H, Takaori-Kondo A, Fukui R, Miyake K, Maeda T,
Kamihira S, Miyachi Y, Uchiyama T. Bortezomib suppresses function and survival of plasmacytoid
dendritic cells by targeting intracellular trafficking of Toll-like receptors and endoplasmic
reticulum homeostasis.
Blood. 2011 Jan 13;117(2):500-9
5. Nakahigashi K, Kabashima K, Ikoma A, Verkman AS, Miyachi Y, Hara-Chikuma M. Upregulation
of Aquaporin-3 Is Involved in Keratinocyte Proliferation and Epidermal Hyperplasia.
J Invest Dermatol. 2010 Dec 30. [Epub ahead of print]
- Clinical Medicine (Core Departments) - Developmental Medicine
Pediatrics
The most important issue at Department of Pediatrics is development. A number of pediatric disorders are derived from the
impairments during developmental process and the investigations disclosing the intrinsic defects lead to the exploitation of new
diagnosis and treatment for intractable diseases. We would like to apply our outcomes obtained from clinic and laboratory to
children with intractable diseases.
Toshio Heike
Professor
❶
●
❷
●
Several projects on stem cell research and
regenerative medicine are on progress. We are
dealing with wide variety of stem cells such as
hematopoietic stem cells, bone marrow-derived
multipotent stem cells, skeketal or cardiac muscle
stem cells, neural stem cells, liver stem cells
including somatic stem cells and embryonic stem
cells in a mouse, monkey and a human. We are
aiming for the clinical application using these cells.
We have developed a new immunocompromised
mouse, NOD/SCID/gamma c null mouse, which
permits the engraftment and reconstitution of
transplanted human cells. The development of this
mouse enabled in vivo evaluation of human stem
cells for the first time, leading to the establishment of ❶ ES-derived satellite-like cells can repair damaged muscle in vivo.
reliable and safe regenerative medicine using human ❷ Selective and efficient detection of latent mutation of CIAS1 gene in mosaic CINCA
syndrome
stem cells.
Pediatrics
Professor
Associate
Professor
Senior
Lecturer
Assistant
Professor
TEL
FAX
e-mail
URL
: Toshio Heike
Recent Publications
: Masahiko Kawai, Ryuta Nishikomori
: Ken-ichiro Watanabe,
: Hiraku Doi, Takahiro Yasumi,
Takeo Kato, Yasunari Yamanaka,
Fusako Niwa, Shinji Kaichi,
Katsutsugu Umeda, Shiro Baba,
Tomonari Awaya, Takeshi Hasegawa
: +81-75-751-3290
: +81-75-752-2361
: [email protected]
~pediatrics/
Kyoto University
1. Morishima T, Watanabe KI, Niwa A, Fujino H, Matsubara H, Adachi S, Suemori H, Nakahata T,
Heike T.: Neutrophil Differentiation From Human-Induced Pluripotent Stem Cells. J Cell Physiol.
2011
2. Kumada T, Yamanaka Y, Kitano A, Shibata M, Awaya T, Kato T, Okawa K, Abe T, Oshima N,
Nakahata T, Heike T.: Ttyh1, a Ca(2+)-binding protein localized to the endoplasmic reticulum, is
required for early embryonic development. Dev Dyn. 2010
3. Kaichi S, Hasegawa K, Takaya T, Yokoo N, Mima T, Kawamura T, Morimoto T, Ono K, Baba
S, Doi H, Yamanaka S, Nakahata T, Heike T. : Cell line-dependent differentiation of induced
pluripotent stem cells into cardiomyocytes in mice. Cardiovasc Res. 2010
4. Mizuno Y, Chang H, Umeda K, Niwa A, Iwasa T, Awaya T, Fukuda S, Yamamoto H, Yamanaka
S, Nakahata T, Heike T: Generation of skeletal muscle stem/progenitor cells from murine induced
pluripotent stem cells. FASEB J 24:2245-2253, 2010.
5. Sakai H, Ito S, Nishikomori R, Takaoka Y, Kawai T, Saito M, Okafuji I, Yasumi T, Heike
T, Nakahata T: A case of early-onset sarcoidosis with a six-base deletion in the NOD2 gene.
Rheumatology 49 : 194-62009.
- Clinical Medicine (Core Departments) - Radiology and Nuclear Medicine
Radiation Oncology and Image-Applied Therapy
We are developing innovative treatment approaches to eradicate cancers which now affect majority of folks. As molecular
biological approaches, we are focusing on hypoxic cells within tumors. We are investigating the cause of radioresistance of the
hypoxic cells and developing methods to overcome the effects of the hypoxia. On the other hand, as physical and engineering
approach, we are driving forward to high-precision radiotherapy such as intensity-modulated radiotherapy and stereotactic
irradiation, and 4-D radiotherapy. We welcome the participation of physicians, biologists, and experts in physical engineering
who are interested in the development of tumor-targeted treatments customized for characteristics of tumors.
Masahiro Hiraoka, M.D., Ph.D.
Professor
■Biological approach
Tumor hypoxia, which is caused by the imbalance between
oxygen-consumption in and oxygen-supply to a cancer,
has been reported to induce radioresistant phenotype of
cancer cells. We have been aiming to elucidate biological
mechanism behind the hypoxia-mediated cancer
radioresistance. Then, based on the obtained information,
we are aiming to develop innovative radiation therapy
strategies for cancer.
1) Imaging of hypoxic regions in solid tumors by using the
reporter construct, 5HRE-Luciferase. We first constructed
reporter genes, which express luciferase bioluminescence
under the control of HIF-1-dependent promoter, 5HRE.
Then, we established a strategy to image tumor hypoxia
as HIF-1-dependent bioluminescence in real-time. The
imaging system has helped us to elucidate molecular
mechanism behind cancer radioresistance and to develop
innovative 4-dimentional radiation therapy and chemoradiation therapy.
2) Development of imaging probes and anti-cancer drugs
for tumor hypoxia. Through the collaboration with various
labs belonging to Graduate School of Pharmaceutical
Science and Engineering, we have developed imaging
probes and anti-cancer drugs to image and target tumor
hypoxia, respectively.
■Physical and engineering approach
We are implementing basic researches and clinical
applications of advanced high-precision radiation therapy
such as intensity-modulated radiotherapy (IMRT),
stereotactic irradiation, and image-guided radiotherapy as a
physical and engineering approach. We are also developing
next-generation 4-dimensional radiotherapy system with
tracking irradiation ability. Our final goal is to develop
methods for so-called tailor-made radiotherapy in which
biological imaging and molecular biological approach are
integrated into physical and engineering approach. In April
2005, we have established a Division of Medical Physics
in our Department consisted of four staffs in order to build
up the framework for both researches and clinical works,
where 4D dose calculation algorithm and in-house Monte
Carlo dose-calculation system is underdevelopment.
Radiation Oncology and Image-Applied Therapy
Professor : Masahiro Hiraoka
Associate
Professor : Michihide Mitsumori, Akira Sawada
Senior
Lecturer : Takashi Mizowaki, Keiko Shibuya
Assistant
Professor : Satoshi Itasaka, Michio Yoshimura,
Yukinori Matsuo, Masakazu Ogura,
Yoshiki Norihisa, Masaru Nrabayashi,
Sayaka Sato, Yuuki Miyabe,
Mitsuhiro Nakamura
TEL
: +81-75-751-3417
FAX
: +81-75-771-9749
e-mail
: [email protected]
URL
: http://radiotherapy.kuhp.kyoto-u.ac.jp
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❶ Immunohistochemical analysis of a section of solid tumor with fluorescence-labeled
antibodies. The green indicates a blood vessel and the red indicates hypoxic tumor cells.
❷ Real time imaging of hypoxic regions in solid tumors via IVIS-SPECTRUM by using
cancer cell lines, which specifically express luciferase under hypoxic conditions.
❸ Orthotopic model for lung cancer : Evaluation of new therapeutic strategy via IVISSPECTRUM.
❹ An example of Intensity Modulated Radiation Therapy (IMRT) for prostate cancer. Using 5
ports of intensity modulated beam, large dose of radiation can be delivered while sparing
radiosensitive organs such as rectum or femoral head.
Recent Publications
1. Nakamura M, Sawada A, Ishihara Y, et al. Dosimetric characterization of a multileaf collimator
for a new four-dimensional image-guided radiotherapy system with a gimbaled x-ray head, MHITM2000, Med. Phys. 37, 4684-.4691, 2010
2. Shiinoki T, Shibuya K, Nakamura M, Nakamura A, Matsuo Y, Nakata M, Sawada A, Mizowaki T,
Itoh A, Hiraoka M Interfractional reproducibility in pancreatic position based on four-dimensional
computed tomography. Int J Radiat Oncol Biol Phys. Oct 2010 (Accepted)
3. Kizaka-Kondoh S, ltasaka S, Zeng L, Tanaka S.Zhao T. Takahashi Y, Shibuya K, Hirota K,
Semenza GL, Hiraoka M. Selective killing of hypoxia-inducible factor-1-active cell improves
survival in a mouse model of invasive and metastatic pancreatic cancer. Clin Cancer Res, 2009,
15:3433-41.
4. Harada H, Itasaka S, Kizaka-Kondoh S, Shibuya K, Morinibu A, Shinomiya K, Hiraoka M. The
Akt/mTOR pathway assures the synthesis of HIF-1alpha protein in a glucose- and reoxygenationdependent manner in irradiated tumors. J. Biol. Chem. 284:5332-5342. 2009.
5. Takayama K, Mizowaki T, Kokubo M, Kawada N, Nakayama H, Narita Y, Nagano K, Kamino Y,
Hiraoka M. Initial validations for pursuing irradiation using a gimbals tracking system. Radiother
Oncol. 93:45-9. 2009
- Clinical Medicine (Core Departments) - Radiology and Nuclear Medicine
Diagnostic Imaging and Nuclear Medicine
The Department of Diagnostic Imaging and Nuclear Medicine, since its establishment in 1976, has committed to teaching
Diagnostic Radiology and Nuclear Medicine, and practice medical services to patients with a variety of diseases on the basis of
imaging. Our Radiology Department provides a full-range of diagnostic services utilizing diagnostic imaging modalities such
as X-ray CT, MRI, Ultrasonography, as well as Positron Emission Tomography, and cover the whole fields of internal organs.
Interventional Radiology that incorporates both diagnosis and treatment is another service which we have been providing. Today,
the Department of Nuclear Medicine and Diagnostic Imaging is leading the way by bringing imaging excellence not only into
various departments within our hospital but also into the community with the achievement of biomedical imaging.
Kaori Togashi, M.D., Ph.D.
Professor
The major research interests of the departmental staff
include:
(1) physical and mathematical investigations for
development of the effective use of imaging modalities,
(2) establishment of a new method of imaging diagnosis
and clinical investigation such as pathological analysis,
and (3) basic medical research using biomedical
and pathological methods to imaging findings.(4)
establishment of a new technology of image-assisted
minimally-invasive therapy. We focus research
activities mainly on clarification of mechanism with
a pathophysiological approach, establishment of a
new method of imaging diagnosis, and development
of state-of-the-art imaging modalities and its clinical
applications. The characteristics of our research are
its wide variety in the field and modality, as a result,
a wide variety of collaboration with departments of
basic sciences, engineering, and medical information.
Although our main concern is clinical problem oriented
researches, we are also concerning with experimental
studies such as development of novel contrast
enhancement, molecular imaging, or an evaluation of
angiogenesis, oxygenation, blood flow in tumors with a
use of state-of-the-art imaging technique.
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Education:
We heartily wish to serve in the field of education
not only for residents who will be a radiologist but
also for residents that are scheduled to be doctors in
other departments. As an option for the residents in
SUPER ROTATION, we are preparing for short courses
consisting of two months to develop their skill in the
imaging diagnosis, because imaging is mandatory in all
the medical fields. Of course, we are waiting for young
doctors to grow them up as professional radiologists
with a program of four years in two institutions to cover
all the major field of body and to be familiar with a
variety of examination.
Diagnostic Imaging and Nuclear Medicine
Professor : Kaori Togashi
Associate
Professor : Toshiya Shibata, Hiroyoshi Isoda
Senior
Lecturer : Yuji Nakamoto, Tomohisa Okada
(Program-Specific Senior Lecturer)
Hiroyuki Sekiguchi
Assistant
Professor : Ryota Fujimoto, Takeshi Kubo,
Mitsunori Kanagaki, Akira Yamamoto,
Shotaro Kanao, Shigeaki Umeoka
(Program-Specific Assistant Professor)
Koji Fujimoto, Masahiro Yakami,
Aki Kido, Toyomichi Shibata,
Masako Kataoka
TEL
: +81-75-751-3760
FAX
: +81-75-771-9709
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~diag_
rad/
Kyoto University
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❶ Fusion image of the tumor, intestine
and vessels of a case of cecal cancer
scheduled for laparoscopic par tial
resection of the colon.
❷ Postoperative case of CABG bypass
with lt-internal thoarcic artery bypassed
to anterior descending branch of ltcoronary artery.
❸ A case of FDG-PET examination for
glucose metabolism in the brain
Recent Publications
1. Kasahara S, Miki Y, Kanagaki M, Yamamoto A, Mori N, Sawada T, Taoka T, Okada T, Togashi K.
Hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with a history
of brain irradiation. Radiology. 2011 Jan;258(1):222-8.
2. Miyake KK, Nakamoto Y, Mikami Y, Ishizu K, Saga T, Higashi T, Togashi K. F-18 FDG PET of
foreign body granuloma: pathologic correlation with imaging features in 3 cases. Clin Nucl Med.
2010 Nov;35(11):853-7.
3. Fujimoto K, Nakai A, Okada T, Ikeuchi T, Satogami N, Daido S, Yakami M, Togashi K. Effect
of hyoscine butylbromide (HBB) on the uterine corpus:quantitative assessment with T2-weighted
(T2W) MRI in healthy volunteers. J Magn Reson Imaging. 2010 Aug;32(2):441-5.
4. Shimada K, Isoda H, Hirokawa Y, Arizono S, Shibata T, Togashi K. Comparison of gadoliniumEOB-DTPA-enhanced and diffusion-weighted liver MRI for detection of small hepatic metastases.
Eur Radiol. 2010 Nov;20(11):2690-8.
5. Umeoka S, Koyama T, Watanabe G, Saga T, Kataoka M, Togashi K, Hatabu H.Preoperative local
staging of esophageal carcinoma using dual-phase contrast-enhanced imaging with multi-detector
row computed tomography: value of the arterial phase images. J Comput Assist Tomogr. 2010 MayJun;34(3):406-12.
6. Yakami M, Ishizu K, Kubo T, Okada T, Togashi K. Development and Evaluation of a Low-Cost and
High-Capacity DICOM Image Data Storage System for Research. J Digit Imaging. 2010 Feb 24.
- Clinical Medicine (Core Departments) - Clinical Bioregulation
Emerging and re-emerging infectious diseases and increasing drug resistance in various pathogenic microorganisms have created
a worldwide interest in infectious diseases. A complex failure in the balance between pathogen, host, and environment causes
infectious diseases. While it is thus very important to establish a correct diagnosis and to administer appropriate treatment for
infectious diseases, it is also very difficult. Our aims are to develop novel diagnostic methodologies and to identify clinical
evidence that will lead to more efficient management of infectious diseases. Our mission is to develop young, promising
clinicians and investigators who will take an active part internationally in the fields of clinical infectious diseases, infection
epidemiology, and clinical microbiology.
Satoshi Ichiyama, M.D., Ph.D.
Professor
Infection is caused by a variety of pathogens from a virion
to a multicellular parasite, while infected hosts show a
range of immunological status from completely healthy to
severely immunocompromised.
Many modalities such as microscopical examination,
culturing, direct detection of antigens or genomes, are now
available for the identification of causative pathogens leading
to the initiation of optimal treatment. However, the correct
cause cannot always be accurately identified, so that there is
a growing need for the development and practical application
of new technologies. To meet this need, we are cooperating
with the clinical laboratory of Kyoto University Hospital and
with many industries for the development and practical use
of novel diagnostic methods for infectious diseases.
Infections in patients who are immunocompromised or
have undergone aggressive surgery are likely to be highly
complicating and life threatening. Effective prevention and
control of nosocomial infections can be expected to result
not only in improved outcomes but also in reduced medical
costs. We are therefore conducting research into a thorough
surveillance of postoperative or post-transplantation
infections as well as into the prevention and control of these
infections.
Unfortunately, the resources for adequate education in
and management of infectious diseases in Japan have
been insufficient compared with those available in other
developed countries. To improve this situation, scientific
rationality, rather than unsubstantiated “authoritative”
comments, must take priority for better practice with regard
to infectious diseases. At Kyoto University Hospital, we
have been providing a sophisticated consultation service
regarding efficient diagnostic procedures and appropriate
management of patients with severe infection, which
has resulted in a steady improvement of the prognosis
for patients with nosocomial sepsis. In addition, we are
educating both medical students and residents in the
management of patients with infectious diseases on the
basis of up-to-date clinical evidence.
We are continuing to pursue the development and application
of novel methods for the diagnosis of infectious diseases,
the control as well as prevention of nosocomial infection
with the aim of putting everyday medical practice regarding
infectious diseases on a foundation of scientific rationality.
Professor : Satoshi Ichiyama
Associate
Professor : Shunji Takakura
Senior
Lecturer : Junko Ito
Assistant
Professor : Takahiro Doi, Miki Nagao,
Aki Matsushima
TEL
: +81-75-751-3502
FAX
: +81-75-751-3233
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/%7Eict/
labmed.html
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❶ To assess the impact of inter vention by
infectious diseases physicians in cases
with Staphylococcus aureus bacteremia, a
retrospective cohort study of patients with SAB,
comparing the management and outcome of
patients during the initial (dashed line) and the
later (solid line) half of the intervention period.
The 30-day mortality significantly decreased in
the later period (solid line).
❷ Suppression of explosive emergence of VRE
in Kyoto Area : Annual surveillance of VRE
since 2005, which about a half of all hospitals
and about a third of long-term care facilities
participated, revealed that emergence and
rapid increase of VRE in Kyoto turned to a
gradual suppression after the promotion of
regional infection control measures with VRE
guidelines.
❸ Molecular epidemiology of vanA- or vanBpositive Enterococcus gallinarum detected in
Kyoto Area. A major clone of vanA- or vanBpositive Enterococcus gallinarum was found
from PFGE analysis. These isolates possessed
vanA gene with the same transposon structure
of vanA-positive E. faecium which had been
detected from multiple hospitals in Kyoto Area.
This implicates that regionwide approach
would be required to suppress the emergence
of VRE capable of spread by horizontal,
interspecies gene transfer of resistance gene.
❹ staffs
Recent Publications
1. Close cooperation between infectious disease physicians and attending physicians results in
better outcomes for patients with Staphylococcus aureus bacteraemia. Nagao M, Iinuma Y, Saito
T, Matsumura Y, Shirano M, Matsushima A, Takakura S, Ito Y, Ichiyama S. Clin Microbiol Infect.
2010;16:1783-8.
2. First outbreak of methicillin-resistant Staphylococcus aureus USA300 harboring the PantonValentine leukocidin genes among Japanese health care workers and hospitalized patients.
Nagao M, Iinuma Y, Suzuki M, Matsushima A, Takakura S, Ito Y, Ichiyama S. Am J Infect Control.
2010;38:e37-9.
3. Regional spread of vanA- or vanB-positive Enterococcus gallinarum in hospitals and long-term
care facilities in Kyoto prefecture, Japan. Shirano M, Takakura S, Yamamoto M, Matsumura Y,
Matsushima A, Nagao M, Fujihara N, Saito T, Ito Y, Iinuma Y, Shimizu T, Fujita N, Ichiyama S.
Epidemiol Infect. 2011;139:430-6.
4. High Prevalence of Mutators in Enterobacter cloacae Nosocomial Isolates and Their Association
with Antimicrobial Resistance and Repetitive Detection. Matsushima A, Takakura S, Fujihara N,
Saito T, Ito Y, Iinuma Y, Ichiyama S. Clin Microbiol Infect. 2009 Dec 23. [Epub ahead of print]
- Clinical Medicine (Core Departments) - Department of Surgery
Gastrointestinal Surgery
Department of Surgery was reorganized into three new divisions in April 2006: Gastrointestinal Surgery, Hepatobiliarypancreas Surgery & Transplantation, and Breast Surgery. Division of Gastrointestinal Surgery focuses on surgical treatments
of gastrointestinal (esophageal, gastric, colorectal) carcinomas, inflammatory bowel diseases and morbid obesity. The division
offers comprehensive surgical education to the medical students and young surgeons, and a strong foundation for basic
surgical research related to the field to the graduate students. Recent advances in laparoscopic surgery have led us to minimally
invasive, yet more refined operation compared with classical open-abdominal surgery. The finest-quality laparoscopic surgeries
performed in our division are reflection of the rigorous surgical training and sturdy basic surgical research.
Yoshiharu Sakai, M.D., Ph.D
Professor
Main topics of surgical researches are as follows:
1) molecular biological analysis of gastrointestinal
carcinomas to estimate the prognosis or the
efficacy of chemoradiotherapy, 2) evaluation of
gastrointestinal physiology after surgical procedures,
3) development of new imaging system to unveil
and understand more details of surgical anatomy,
4) development of novel surgical procedures and
surgical instruments, 5) active involvement in
the multi-institutional clinical studies to evaluate
outcome of the surgical treatments. Laparoscopy
and thoracosopy have provided the clear, magnified
view even in the narrowest of the human body space
and contributed to disclose the surgical anatomy
beyond what was once thought the limitation of
the human eyes. The new surgical procedures with
less damage on the surrounding organs or tissues
would be grounded on the new imaging technique
that could detail the surgical anatomy to the levels
previously unseen. These new procedures must be
further evaluated with the physiological examination
and the clinical outcome examination. A rigorous
surgical training program and firm basic surgical
research are fundamental to obtain the best possible
clinical outcome. It is critical for surgical trainees to
learn from the video of the exquisite operation and to
be guided by a skillful, experienced surgeon. We are
confident that our program provides both of these in
the finest quality.
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❶ Lymphangiogenesis in cancer metastasis
❷ The signaling pathway of anti-cancer effect of INF gamma
❸ The role of chemokines during metastais of colon cancer
❹ The interaction of cancer stem cells and mesenchymal cells
❺ The induction of cancer stem cells by mesenchymal cells
Surgery
Division of Gastrointestinal Surgery
Professor : Yoshiharu Sakai
Associate
Professor : Hiroshi Okabe
Senior
Lecturer : Suguru Hasegawa
Assistant
Professor : Junichiro Kawamura,
Kazutaka Obama, Kenji Kawada,
Eiji Tanaka, Shigeru Tsunoda,
Masahiro Yamada
TEL
: +81-75-751-3650
FAX
: +81-75-751-3219
e-mail
: [email protected]
Kyoto University
Recent Publications
1. Kawamura J, Nagayama S, Nomura A, Itami A, Okabe H, Sato S, Watanabe G, Sakai Y. Long-term
outcomes of peripheral arm ports implanted in patients with colorectal cancer. Int J Clin Oncol.
13:349-54, 2008.
2. Hosogi H, Nagayama S, Kawamura J, Koshiba Y, Nomura A, Itami A, Okabe H, Satoh S, Watanabe
G, Sakai Y. Molecular insights into Peutz-Jeghers syndrome: two probands with a germline
mutation of LKB1. J Gastroenterol. 43:492-7, 2008.
3. Okoshi K, Kubo H, Nagayama S, Tabata C, Kadokawa Y, Hisamori S, Yonenaga Y, Fujimoto A,
Mori A, Onodera H, Watanabe G, Sakai Y. All-trans-retinoic acid attenuates radiation-induced
intestinal fibrosis in mice. J Surg Res. 150: 53-59, 2008.
4. Hisamori S, Tabata C, Kadokawa Y, Okoshi K, Tabata R, Mori A, Nagayama S, Watanabe G, Kubo
H, Sakai Y. All-trans-retinoic acid ameliorates carbon tetrachloride-induced liver fibrosis in mice
through modulating cytokine production. Liver Int. 28: 1217-1225, 2008.
Hepato-pancreato-biliary Surgery and Transplantation
In our Division of Hepato-Biliary-Pancreatic Surgery & Transplantation, we are practicing multi-modality treatments consisting
of surgical operation, chemotherapy, irradiation and others for patients with hepato-biliary and pancreatic malignancies. Even
against difficult-to-treat advanced cancers, we are currently undertaking extension of surgical indication based on the latest
outcomes of clinical studies and experienced surgical skills. On the other hand, we are introducing minimally invasive surgery
such as laparoscopic surgery for both benign and malignant diseases. Liver transplantation for the treatments of end-stage
liver failure and hepatic malignancies is the most significant feature of our division. As a worldwide leader in the field of liver
transplantation, we are proud of clinical outcomes of our series. It is our goal to lead surgeons of tomorrow through researches
with substantial feedback toward clinical practices and by intensive training of surgical skills.
Shinji Uemoto, M.D., Ph.D.
Professor
In hepato-biliary surgery, the studies concerning
development of molecular-targeted therapy against
hepatocellular carcinoma, mechanism of chemotherapyinduced liver injury, and molecular mechanism of liver
fibrosis are conducted. Concerning the realization of
regenerative medicine for liver diseases, we execute
experiments for differentiation and cell transplantation of
several kinds of stem/progenitor cells, for example, ES
cells, iPS cells, hepatic stem cells, and hepatic progenitor
cells. Furthermore, we are also going to focus on the
identification and characterization of cancer stem cells of
liver and pancreatic cancer. To improve clinical outcome
of pancreatic cancer, we are actively undertaking the
international collaborative study on precursors to pancreatic
cancer including pancreatic intraepithelial neoplasia
(PanIN) and intraductal papillary mucinous neoplasm
(IPMN). In our research group of pancreatic regeneration,
we have shown that dosage of Ptf1a plays an important
role in cell fate determination among pancreatic/ bile
duct/ and duodenal lineages during organogenesis. We
are presently investigating the mechanisms involved in
maintenance of pancreatic duct epithelium, which may
lead to a breakthrough in pancreatic carcinogenesis to the
treatment of pancreatic cancer as our ultimate goals. We
have islet transplantation program both in clinical practice
and in basic research, which is mainly focused on islet
isolation, preservation and transplantation. In the liver
transplantation, we have been executing various basic/
clinical researches to solve the crisis of donor shortage:
Development of “Chimeric liver” using xenogenic hepatic
architecture as “scaffold” with replacement of human
hepatocytes; Mesenchymal stem cell transplantation
with liver transplantation, anticipating various protective
and regenerative effects to small/damaged liver grafts;
Development of novel strategy/algorithm for intensive
portal venous pressure with an emphasis of liver-resident
regulatory T-cells; Development of a novel perfusion
preservation of liver grafts, accompanied with new concepts
of graft “Post-conditioning”.We support graduate students
not only to laboratory research, but also to learn advanced
medicine and to study abroad. Conferring the degree, they
can play active parts in education, research and clinic.
Hepato- Biliary-Pancreatic Surgery and
Transplantation
Professor : Shinji Uemoto
Associate
Professor : Toshimi Kaido
Senior
Lecturer : Kyoichi Takaori, Yoshiya Kawaguchi,
Etsuro Hatano
Assistant
Professor : Akira Mori, Masaki Mizumoto,
Yasuhiro Ogura, Yasuhiro Iwanaga,
Kentaro Yasuchika, Kojiro Taura,
Toshihiko Masui, Koichiro Hata,
Masayuki Koizumi, Jun Yoshizawa
TEL
: +81-75-751-3651
FAX
: +81-75-751-3106
e-mail
: [email protected]
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❶ JNK inhibitor suppressed rat DEN-induced HCC (Hepatology, 49:1944-53, 2009)
❷ Contribution of mouse embryonic stem cell-derived hepatocytes to regeneration of
damaged-model mouse liver after cell transplantation. (Stem Cells. 2007 Dec;25
(12):3252-60.)
❸ Ptf1a as an important factor in cell fate determination among pancreatic/ bile duct/ and
duodenal lineages during organogenesis.
❹ Islet transplantation
❺ Chimeric Liver: Luminescence and Albumin
Recent Publications
1. Iwaisako, K., Hatano, E., Taura, K., et al. Loss of Sept4 exacerbates liver fibrosis through the
dysregulation of hepatic stellate cells. J Hepatol 49 (5):768-778, 2008
Narita M., Hatano, E., Ikai, I., et al. A phosphodiesterase III inhibitor protects rat liver from
sinusoidal obstruction syndrome through heme oxygenase-1 induction. Ann Surg, 249 (5):806-13,
2009
2. In vitro hepatic maturation of human embryonic stem cells by using a mesenchymal cell line
derived from murine fetal livers.
Ishii T, Yasuchika K, Fukumitsu K, Kawamoto T, Kawamura-Saitoh M, Amagai Y, Ikai I, Uemoto
S, Kawase E, Suemori H, Nakatsuji N. Cell Tissue Res. 2010 Mar;339(3):505-12.
3. Fukuda A, Kawaguchi Y, Furuyama K, et al.
Reduction of Ptf1a gene dosage causes pancreatic hypoplasia and diabetes in mice.
Diabetes. 2008;57(9):2421-31.
4. Toyoda K, Okitsu T, Yamane S, Uonaga T, Liu X, Harada N, Uemoto S, Seino Y, Inagaki K.
GLP-1 receptor signaling protects pancreatic beta cells in intraportal islet transplant by inhibiting
apoptosis. Biochem Biophys Res Com 2008, 367(4), 793-8.
5. 1. Liver Transpl. 2010 Apr;16(4):538-40.
Usefulness of the Kyoto criteria as selection criteria for living donor liver transplantation for
hepatocellular carcinoma.
Kaido T, Takada Y, Uemoto S.
Breast Surgery
Among Japanese females, the incidence of breast cancer is the highest amongst all cancers. The incidence and mortality rate of
breast cancer are rising every year, and it has been demonstrated that these trends differ between Asia and the West. Furthermore,
there is a drastic increase in the importance of breast cancer research in this country. In our research group, studies ranging
from molecular biological research to clinical trials are performed with the aim of creating a system for optimization and
individualization of treatment by means of profound and overall understanding of characteristics of each patient. Novel tools for
local therapy and diagnosis are also being investigated extensively. Furthermore, studies of breast cancer prevention according
to an individual’s risk profile are being initiated to create a platform for holistic medicine.
Masakazu Toi M.D. Ph.D
Professor
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For optimization and individualization of
breast cancer treatment based on the concept
of multidisciplinary therapy, studies are being
performed to create a system for assessing the
relationship between biological characteristics
of tumours and host and to develop therapeutic
algorithms. The analyses of biomarkers include those
for gene amplification, gene polymorphism, gene
mutation, protein manifestation and phosphorylation.
The development of therapeutic algorithms focuses
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on integrating informatics using laboratory data,
pathological findings and clinical information and
outcomes.
Current breast cancer studies in our group, such those
concerning basic science, translational research and
clinical trials, include the following:
* Breast cancer stem cell and adipose stem cell study
* Biomarker study for optimizing systemic and local
therapy
* Study of circulating tumour cells, endothelial cells
and immune cells
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* Clinical development and application of bio-optical
devices
* Development of a novel and less invasive therapy
* Study of treatment algorithms for breast cancer
patients
We work enthusiastically not only for breast cancer
patients but also for further education of young
medical doctors and investigators. We are interested
in developing international collaborations. We
are seeking exceptional, interactive and creative
❶ Human adipose tissue-derived stem cells (left) and adipocytes induced by it (right, oil red
scientists and physicians to develop novel breast
O staining)
cancer research and new treatment paradigms.
❷ Mammosphere, containing breast cancer stem like cells
Breast Surgery
Professor : Masakazu Toi
Associate
Professor : Tomoharu Sugie,
(Program-Specific)
Kitai Toshiyuki
Senior
Lecturer : Hiroshi Ishiguro
Assistant
Professor : Takayuki Ueno,
Megumi Takeuchi,
(Program-Specific)
Wakako Tsuji
TEL
: +81-75-751-3660
FAX
: +81-75-751-3616
e-mail
: [email protected]
URL
: http://www.brca.jp/
Kyoto University
❸ laboratory staff room
❹ laboratory room
❺ Operation
❻ CTC(Circulating Tumor Cell) analysis
Recent Publications
1. Ali AM, Toi M, Ueno T. Anti-angiogenic cancer therapy updates. Curr Mol Med. 9:954-66, 2009.
2. Tsuji W, Inamoto T, Yamashiro H, et al. Adipogenesis induced by human adipose tissue-derived
stem cells. Tissue Eng Part A. 15:83-93, 2009.
3. Toi M, Iwata H, Fujiwara Y, et al. Lapatinib monotherapy in patients with relapsed, advanced, or
metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II
studies. Br J Cancer 101:1676-82, 2009.
4. Toi M. Long-term outcomes of aromatase inhibition for breast cancer. Lancet Oncol 9: 8-9, 2008
5. Ueno T, Elmberger G, Weaver TE, et al. The aspartic protease napsin A suppresses tumor growth
independent of its catalytic activity. Lab Invest. Mar;88(3):256-63. Epub 2008
- Clinical Medicine (Core Departments) - Clinical Sciences for Surgical Stresses
Anesthesia
The original purpose of anesthesiology was reduction of surgery-induced pain. However, the present goal of anesthesiology
is control of excessive biological responses induced by a variety of stresses and protection of patients from stress-induced
complications. Clinical activity of this department is divided into anesthesia in the operation theater, pain control for a variety of
diseases and critical care medicine. We aim to protect a living body from stresses including surgical stresses, pain, injuries and
inflammation for the benefit of patients. Our ultimate goal is elucidation of mechanism for stress responses and development of
treatment and care for suppression of excessive stress responses.
Kazuhiko Fukuda, M.D., Ph.D.
Professor
The goal of research in this department is to elucidate
mechanisms of responses induced by a variety of stresses and
to develop management to control stress responses. Anesthetics
and opioids have long been used to suppress stress responses
induced by surgical stresses, and are clinically indispensable
drugs today. However, the mechanisms of action of these
drugs have not been completely understood. We are analyzing
actions of anesthetics and opioids from many aspects. To
analyze pharmacological actions of opioids at the molecular
level, we have cloned cDNAs of opioid receptors, and have
analyzed intracellular signal transduction mechanisms activated
by opioids. Using genetically engineered mice, we are testing
the role of the opioid receptor family in the pharmacological
actions of inhaled anesthetics, and have demonstrated the
possible involvement of the nociceptin receptor and the
kappa-opioid receptor in the analgesic action of nitrous oxide.
We have shown that benzodiazepines and local anesthetics
potentiate corticotropin releasing factor-induced transcription
of the proopiomelanocortin gene. During perioperative period,
oxygen supply is often reduced by anemia and changes in
the cardio-respiratory system, and organs are exposed to
hypoxia, which induces hypoxic responses at the organ, cellular
and molecular levels. We have analyzed hypoxia-inducible
factor (HIF), which plays important roles in cellular hypoxic
responses, and demonstrated that perioperatively used drugs
and hypothermia can change cellular hypoxic responses by
affecting HIF activity and gene expression controlled by HIF.
The clinical research group in this department is attempting to
develop comfortable anesthetic care for ambulatory surgery and
automatic control of intravenous anesthesia.
This department is responsible for instruction and clinical
training of anesthesiology and critical care medicine for
undergraduate and postgraduate students. Residents are trained
to obtain the basic capability of life support and anesthetic care
in the operation room. Doctors aiming to be board certified
anesthesiologists are trained for anesthetic management of
special operations, intensive care for various systemic diseases
and control of pain caused by various diseases.
Anesthesia
Professor : Kazuhiko Fukuda
Associate
Professor : Toshiyuki Arai
Senior
Lecturer : Hajime Segawa, Kiichi Hirota,
Jiro Kurata
Assistant
Professor : Masahiro Kakuyama,
Hidekatsu Furutani, Hisanari Ishii,
Takehiro Shoda, Hiroshi Tsujikawa,
Keiji Tanimoto, Taizo Hisano,
Tomoharu Tanaka, Toshiyuki Mizota,
Masami Sato, Katsunori Yokoyama
: Makiko Ikeura, Tomohiro Koyama,
Toshie Habara
TEL
: +81-75-751-3433
FAX
: +81-75-752-3259
e-mail
: [email protected]
URL
: http://anesthesia.kuhp.kyoto-u.ac.jp/
❶
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❸
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❹
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❶ Predicted structure of the opioid
receptors.
Cloning of the cDNAs and
determination of the amino acid
sequences demonstrated that the
opioid receptors belong to the seven
transmembrane receptor family.
❷ Intracellular signal transduction
mechanism mediated by the opioid
receptors.
Activation of the opioid receptors
i n d u c e s a va r i e t y o f c e l l u l a r
responses, including inhibition of
adenylate cyclase, activation of the
inwardly rectifier K+ channel and
inhibition of the voltage-dependent
Ca2+ channel, via activation of the
G-protein. Furthermore, activation
of mitogen-activated protein kinases
by the opioid receptors leads to
changes in gene expression and
activation of phospholipase A2.
❸ E f fe c t s o f a n e s t h e t i c s o n t h e
hypoxia-inducible factor (HIF).
Propofol, an intravenous anesthetic,
inhibits lipopolysaccharide-induced
HIF-1 activation and changes in
glucose metabolism in macrophage,
by suppressing translation of HIF1alpha from mRNA.
❹ Clinical anesthesia in the operating
theater
Staffs of the department of
anesthesia perfor m anesthetic
management and teach residents in
the operating theater.
Recent Publications
1. Koyama, T., Mayahara, T., Wakamatsu, T., Sora, I. and Fukuda, K.: Deletion of mu-opioid receptor
in mice does not affect the minimum alveolar concentration of volatile anesthetics and nitrous
oxide-induced analgesia. Br. J. Anaesth. 103, 744-749 (2009).
2. Tsujikawa, H., Shoda, T., Mizota, T. and Fukuda, K.: Morphine induces DNA damage and P53
activation in CD3+ T cells. Biochim. Biophys. Acta 1790, 791-799 (2009).
3. Tanaka, T., Wakamatsu, T., Daijo, H., Oda, S., Kai, S., Adachi, T., Kizaka-Kondoh, S., Fukuda,
K. and Hirota, K.: Persisting mild hypothermia suppresses hypoxia-inducible factor 1a protein
synthesis and HIF-1-mediated gene expression. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298,
R661-671 (2010).
4. Tanaka, T., Takabuchi, S., Nishi, K., Oda, S., Wakamatsu, T., Daijo, H., Fukuda, K. and Hirota, K.:
The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia-inducible factor
1 activation and suppresses the glucose metabolism in macrophages. J. Anesth. 24, 54-60 (2010).
5. Koyama, T. and Fukuda, K.: Involvement of the k-opioid receptor in nitrous oxide- induced
analgesia in mice. J. Anesth. 24, 297-299 (2010).
- Clinical Medicine (Core Departments) - Surgery for Visceral Organs
In the clinical field of obstetrics and gynecology, we manage physiological and psychological problems during the entire
women’s life toward which all medical doctors should face. In addition, obstetricians and gynecologists manage specialized
field of pathophysiology; i.e. pregnancy and disease of female pelvic organs. In our department of gynecology and obstetrics, all
postgraduate residents can learn characteristics of female pathophysiology, and can acquire basic knowledge about primary care
in obstetric and gynecological emergency. In the research field, obstetrics and gynecology contain various research issues such
as perinatology, gynelocogical oncology and reproductive pathophysiology.
Ikuo Konishi, M.D.
Professor
❶
●
Our department covers the field of perinatology, gynecological
oncology and reproduction. Clinical and research issues which
across these fields are discussed among staffs and research
fellows in each field.
■Perinatology:
In the clinical department of perinatology, we manage patients
with high risk pregnancy, fetal anomalies, and with various
medical complications. In the field of perinatology, we are
investigating the mechanisms of parturition such as regulation
of uterine contraction and cervical ripening by prostaglandins
or nitric oxide produced in utero. We are also interested in
the regulatory mechanisms of fetal development, concerning
about feto-maternal energy metabolism, especially in relation
to placenta and adipocyte derived factors including leptin and
resistin.
■Gynecological oncology:
Clinical principle is to select most suitable treatment strategy
for each patient. To achieve this purpose, we discuss the results
of image diagnosis and pathological diagnosis with radiologists
and pathologists in each case. In addition, we have established
bloodless and bladder function-preserved radical hysterectomy,
which is standard surgical procedure for invasive cervical
cancer. In the research field, leiomyoma and ovarian cancer cell
lines established in our department are investigated to clarify
the tumorgenesis of uterine smooth muscle tumor and ovarian
cancer. In addition, new approach of anti-cancer drug delivery
system, analyses of immuno-escaping mechanism of cancer and
the development of anti-cancer immunotherapy using dendritic
cells are undergone.
■Reproduction:
We offer a complete spectrum of infertility treatments
including In Vitro Fertilization (IVF) and other Assisted
Reproductive Technologies. Laparoscopic surgeries are also
performed for the infertile women. In the research field, we
are interested in ovulation, implantation and placentation;
which are all important processes for the establishment of
successful pregnancy. To clarify pathophysiology of these
processes, we are now investigating the regulatory mechanisms
of folliculogenesis and corpus luteum formation in the
ovary, identification of molecules which regulate successful
implantation, the mechanisms of controlled invasion of
placental extravillous trophoblasts into maternal uterus and the
regulatory mechanisms of immune factor in implantation.
Professor : Ikuo Konishi
Associate
Professor : Hiroshi Fujiwara
Senior
Lecturer : Masaki Mandai, Keiji Tatsumi,
Kenzo Kosaka
Assistant
Professor : Yukiyasu Sato, Ayako Suzuki,
Noriomi Matsumura, Tsukasa Baba,
Kazuyo Kakui, Eiji Kondo,
Junzo Hamanishi, Shogo Yamamura,
Yumiko Yoshioka
TEL
: +81-75-751-3269
FAX
: +81-75-761-3967
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~obgy/
Kyoto University
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❶ Leptin produced by placental trophoblast is involved in the regulation of fetal-maternal metabolism.
❷ Transformed human ovarian surface epithelial cells formed tumors in the injected mice.
❸ Laeverin, a novel membrane bound aminopeptidase we have cloned from cDNA library derived from
human chorion laeve, is specifically expressed on extravillous trophoblast in human implantaton site.
VT, villous trophoblasts; EVT, extravillous trophoblasts.
Recent Publications
1. “Oncogenic property of acrogranin in human uterine leiomyosarcoma: direct evidence of genetic contribution in
in vivo tumorigenesis ”
N.Matsumura, M.Mandai, M.Miyanishi, K.Fukuhara, T.Baba, T.Higuchi, M.Kariya, K.Takakura, and S.Fujii
Clin Cancer Res. 2006 Mar 1;12(5):1402-11.
2. “Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression ”
M.Miyanishi, M.Mandai, N.Matsumura, K.Yamaguchi, J.Hamanishi, T.Higuchi, K.Takakura and S.Fujii
Oncol Rep. 2007 Feb;17(2):329-33.
3. “Immune cell contribute to systemic cross-talk between the embryo and mother during early pregnancy in
cooperation with the endocrine system”
H.Fujiwara
Reproductive Medicine and Biology, 5:19-29, 2006
4. “Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in
patients with repeated failure of IVF-embryo transfer”
S.Yoshioka, H.Fujiwara, T.Nakayama, K.Kosaka, T.Mori and S.Fujii
Human Reproduction,21(12):3290-3294,2006
5. “Eph-ephrin A System Regulates Murine Blastocyst Attachment and Spreading”
H.Fujii, K. Tatsumi, K.Kosaka, S.Yoshioka, H.Fujiwara and S.Fujii
Developmental Dynamics, 235:3250-3258,2006
6. “ Integrin alpha5 is involved in fibronectin-induced human extravillous trophoblast invasion ”
BX Zeng, H.Fujiwara, Y.Sato, Y.Nishioka, S.Yamada, S.Yoshioka, M.Ueda, T.Higuchi and S. Fujii
J Reprod Immunol. 2007 Feb;73(1):1-10. Epub 2006 Oct 5.
7. “ Precise anatomy of the vesico-uterine ligament for radical hysterectomy ”
S.Fujii, K.Takakura, N.Matsumura, T.Higuchi, S.Yura, M.Mandai and T.Baba
Gynecol Oncol. 2007 Jan;104(1):186-91. Epub 2006 Sep 22.
8. “Differences in maternal plasma leptin concentration during human pregnancy, induced labor, after cesarean
section without labor and vaginal deliveries: A review.”
M. Nuamah, S. Yura, N. Sagawa, H. Itoh and S. Fujii
Nepal Journal of Obstetrics & Gynecology, 1: 13-7, 2006
9. “Increased cyclooxygenase-2 expression is correlated with suppressed antitumor immunity in cervical
adenocarcinomas”
Chen TH, Fukuhara K, Mandai M, Matsumura N, Kariya M, Takakura K, Fujii S
Int J Gynecol Cancer 16(2):772-779, 2006.
10. “Undernutrition inutero augments systolic blood pressure and Cardiac Remodeling in Adult Mouse OffspringPossible Involvement of Local Cardiac Angiotensin System in Developmental Origins of Cardiovascular
Disease-Endocrinology”
M.Kawamura, H.Itoh, S.Yura, H.Mogami, S.Isuga, H.Makino, Y.Miyamoto, Y.Yoshimasa, N.Sagawa and S.Fujii
Endocrinology. 2007 Mar;148(3):1218-25. 2006.
Urology
Urology comprehends a wide range of medical field. Among them, the main interests of our department are in urologic oncology,
and in benign diseases including voiding function, transplantation, reproductive medicine, and pediatric urology.
In urologic oncology, in particular, we have a long track record of having introduced innovative therapies such as new anticancer
drug treatments for urogenital tumors, new types of operation for urinary diversion, and laparoscopic urologic surgeries, of
which we have taken the leadership in Japan.
The basic policy of our department is to carry out the advanced medicine based on active propulsion of research and education.
We offer, not only the standard medical treatments, but highly advanced medical treatments to the patients by constantly
introducing the state-of the-art technology and updated knowledge of the time.
Osamu Ogawa, M.D., Ph.D
Professor
❶ Laparoscopic urologic surgery
❶
●
Urology
Professor : Osamu Ogawa
Associate
Professor : Hiroyuki Nishiyama
Senior
Lecturer : Akihiro Kanematsu, Koji Yoshimura,
Tomomi, Kamba
Assistant
Professor : Kazutoshi Okubo, Takahiro Inoue,
Yousuke Shimizu, Yoshiyuki Matsui,
Masaaki Imamura
TEL
: +81-75-751-3325
FAX
: +81-75-761-3441
e-mail
: [email protected]
URL
: http://www.urology.kuhp.kyoto-u.ac.jp/
Minato N, Nakamura E. Kobayashi T, Inoue T, Shimizu Y, Terada N, Maeno A, Kajita Y, Yamasaki
T, Kamba T, Toda Y, Mikami Y, Yamada T, Kamoto T, Ogawa O, Nakamura E. SPA-1 controls the
invasion and metastasis of human prostate cancer. Cancer Sci. 2011 (in press)
2. Akamatsu S, Takata R, Ashikawa K, Hosono N, Kamatani N, Fujioka T, Ogawa O, Kubo M,
Nakamura Y, Nakagawa H. Hum Mol Genet. A functional variant in NKX3.1 associated with
prostate cancer susceptibility down-regulates NKX3.1 expression. 2010, 9:4265-72.
3. Kobayashi T, Inoue T, Shimizu Y, Terada N, Maeno A, Kajita Y, Yamasaki T, Kamba T, Toda Y,
Mikami Y, Yamada T, Kamoto T, Ogawa O, Nakamura E. Activation of Rac1 is closely related
to androgen-independent cell proliferation of prostate cancer cells both in vitro and in vivo Mol
Endcrinol, 2010, 24: 722-34.
4. Terada N, Shimizu Y, Kamba T, Inoue T, Maeno A, Kobayashi T, Nakamura E, Kamoto T, Kanaji
T, Maruyama T, Mikami Y, Toda Y, Matsuoka T, Okuno Y, Tsujimoto G, Narumiya S, Ogawa O.
Identification of EP4 as a potential target for the treatment of castration-resistant prostate cancer
using a novel xenograft model. Cancer Res, 2010, 70: 1606-15.
5. Imamura M, Negoro H, Kanematsu A, Yamamoto S, Kimura Y, Nagane K, Yamasaki T, Kanatani
I, Ito N, Tabata Y, Ogawa O. Basic fibroblast growth factor causes urinary bladder overactivity
through gap junction generation in the smooth muscle. Am J Physiol Renal Physiol 2009, 297:F4654. 2009
❷ Mouse bear ing xenograft
As an important part of the surgical section, we try
established from clinical cancer
to bring up top quality urologists with sophisticated
specimen
surgical techniques, who can analyze complicated
❸ Molecular cellular approach to
pathology of urological diseases properly and manage
the urological diseases as a
appropriate treatments for the patients. We believe that
backbone of the basic research
this task will be efficiently achieved by performing
❹ The members of our department
practice of advanced medicine in an education-oriented
environment.
We have maintained a largest number of endourological
surgery, including laparoscopic surgery, in Japan.
Therefore, we believe that we can offer an optimal
educational environment to young physicians trained as
urologic surgeons and educator. Actually, we run a new
education program for specialty training in cooperation
with the affiliated hospitals since 2006.
❷
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On research field, we prioritize the practical science
that can contribute to real medical treatments. In our
lab, more than 10 postgraduate students are engaged in
urologic research, and continue to send the high quality
results to prestigious international journals. In our major
fields such as urologic oncology, voiding function,
transplantation, or reproductive medicine, we encourage
collaboration with various basic research sections in our
university and the foreign laboratories.
In addition, we always have several young urologists
engaged in research abroad, who will contribute to
maintain the research activity at the top-level of the
world.
❹
In the research area of urological oncology, we have ●
made substantial contribution in the elucidation of the
carcinogenic mechanism by using molecular biological
methods and the determination of the hereditary
cancer risk using molecular epidemiological approach.
Recently, we are also actively working with a more
clinically relevant anima model system, patientderived xenograft model in mice. In the area of benign
diseases, we have conducted researches on kidney
transplantation as well as the outstanding studies on
regeneration of the lower urinary tract. More recently,
we are now making innovative achievements in the
field of voiding dysfunction, by introducing molecular
cellular biological approach in this field. In the area Recent Publications
of andrology, we conduct basic researches on the 1. Shimizu Y, Hamazaki Y, Hattori M, Doi K, Terada N, Kobayashi T, Toda Y, Yamasaki T, Inoue TA,
mechanism of male infertility.
Kajita Y, Maeno A, Kamba T, Mikami Y, Kamoto T, Yamada T, Kanno T, Yoshikawa K, Ogawa O,
We take charge of surgical treatment for all categories of cardic diseases (ischemic, valvular and congenital) and vascular
diseases (aortic and peripheral). Our goal is to improve clinical outcomes not only by refining on the established surgical
methods, but also introducing novel concepts evolved from basic researches.
Ryuzo Sakata
Professor
We conduct patients-oriented researches which
are directed toward patients' clinical benefit. Our
main topic is the development of novel therapeutic
methods for end-stage heart failure. Under this
topic, we are undergoing experiments concerning
heart transplantation, assist circulation, myocardial
regeneration, myocardial protection and therapeutic
angiogenesis. Collaboration is actively carried
out with Frontier Science Research Institute,
Translational Research Center, Other Universities
and Centers. We also focus on translational
researches. Based on animal experiments, we are
conducting clinical trial of therapeutic angiogenesis
to treat limb ischemia by sustained release of bFGF
using gelatin hydrogel. We convinced that the
experiences of the basic research and the ability to
solve problems help young surgeons in their further
clinical training.
❶
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❶ Scene in the operating room. Cooperation with cardiologists, anesthesiologist, and comedicals yields excellent surgical results.
❷ Various aspects of cardiovascular surgery. (Left) Left ventricular repair for severely failing
heart. (Upper middle) Off-pump CABG has expanded the surgical indication for coronary
reconstruction. (Lower middle) obotic surgery is expected to play an important role in the
near future. (Right) Cell transplantation for heart failure is one of our researches on the
regenerative therapy.
❸ Clinical and Laboratory staffs
Professor : Ryuzo Sakata
Associate
Professor : Tadashi Ikeda
Senior
Lecturer : Senri Miwa
Assistant
Professor : Kazuhiro Yamazaki, Kenji Minakata,
Tomohiro Nakata, Hiroyuki Muranaka
AssociateProfessor (Translational Research Center)
: Akira Marui
AssistantProfessor (Translational Research Center)
: Shigeki Yanagi
TEL
: +81-75-751-3780
FAX
: +81-75-751-3098
e-mail
: [email protected]
URL
~cardiovasc_surg/
Kyoto University
Recent Publications
1. Bir SC, Esaki J, Marui A, Sakaguchi H, Kevil CG, Ikeda T, Komeda M, Tabata Y, Sakata R.
Therapeutic Treatment with Sustained-Release Platelet-Rich Plasma Restores Blood Perfusion
by Augmenting Ischemia-Induced Angiogenesis and Arteriogenesis in Diabetic Mice. J Vasc Res.
2010;48:195-205
2. Yanagi S, Matsumura K, Marui A, Morishima M, Hyon SH, Ikeda T, Sakata R. Oral pretreatment
with a green tea polyphenol for cardioprotection against ischemia-reperfusion injury in an isolated
rat heart model. J Thorac Cardiovasc Surg. 2011;141:511-7
3. Muranaka H, Marui A, Tsukashita M, Wang J, Nakano J, Ikeda T, Sakata R. Prolonged mechanical
unloading preserves myocardial contractility but impairs relaxation in rat heart of dilated
cardiomyopathy accompanied by myocardial stiffness and apoptosis. J Thorac Cardiovasc Surg.
2010:916-22
4. Morishima M, Marui A, Yanagi S, Nomura T, Nakajima N, Hyon SH, Ikeda T, Sakata R.
Sustained release of vancomycin from a new biodegradable glue to prevent methicillin-resistant
Staphylococcus aureus graft infection. Interact Cardiovasc Thorac Surg. 2010;11:52-5
5. Shimamoto T, Marui A, Nagata Y, Sato M, Saito N, Takeda T, Ueda M, Ikeda T, Sakata R,
Inoue K. A novel approach to prevent spinal cord ischemia: Inoue stent graft with a side branch
of small caliber for the reconstruction of the artery of Adamkiewicz. J Thorac Cardiovasc Surg.
2010;139:655-9
Thoracic Surgery
Department of Thoracic Surgery, Kyoto University, was founded in 1941 and involved into a leading international thoracic
surgery program from one of the earliest such programs in Japan. Clinically, we are dealing with various diseases of the lung
and mediastinum. For increasing lung cancer surgery, video-assisted thracoscopic surgery has become a standard approach
in our department. A new Kyoto Lung Transplant Program was developed by Professor Date who had done a majority of
lung transplants in Japan. Between June 2008 and December 2009, the new program performed living-donor lobar lung
transplantation in eight sick patients resulting in all success. We have accepted a number of foreign visitors for observing such
operation. Thoracic surgeons trained in our department are practicing in affiliated hospitals mainly in the west part of Japan.
Over 2,300 cases of lung cancer surgery (about 10% of cases in whole Japan) are performed annually by our group.
Hiroshi Date, M.D., Ph.D.
Professor
Faculty research within the Department of Thoracic
Surgery encompasses a wide range of interests
including lung cancer, lung transplantation and
regenerative medicine. For lung cancer research, we
are looking for prognostic factors after lung cancer
surgery using specimens removed in OR. Especially,
EGFR mutations and EML4-ALK fusion gene have
been extensively investigated in our laboratory.
Preoperative as well as postoperative chemotherapy
and/or chemo-radiotherapy for lung cancer have
been studied both in the clinic and in the laboratory
so as to identify useful biological makers for “order
made treatment”. For lung transplant research, we
have developed ET-Kyoto solution for preservation
and this solution is now clinically used in various
institutions. We are conducting studies on lung
transplantation from donors after cardiac death using
an ex-vivo lung perfusion animal model. We have
found that forced oscillation technique may be useful
in detecting rejection after lung transplantation.
We first successfully performed a bilateral native
lung sparing living-donor lobar lung transplantation
which can be applied to large adult recipients. The
Department of Thoracic Surgery provides education
and treatment of the full range of complex general
thoracic problems regarding diagnoses, examinations
and surgical and non-surgical therapies.
❶
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❷
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❹
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❶ Lung transplantation
❷ Bilateral native lung sparing living-donor lobar lung transplantation
❸ Ex-vivo lung perfusion model
❹ Novel EML4-ALK variants
❺ Department picture
Thoracic Surgery
Professor : Hiroshi Date
Associate
Professor : Zhenglong Huang
Senior
Lecturer : Hiroaki Sakai, Makoto Sonobe
Assistant
Professor : Tsuyoshi Shoji, Fengshi Chen,
Toshihiko Sato
TEL
: +81-75-751-4975
FAX
: +81-75-751-4974
e-mail
: [email protected]
URL
: http://www.thoracic-kyoto-u.gr.jp/
Recent Publications
1. Date H, et al. Improved survival after living-donor lobar lung transplantation. J Thorac Cardiovasc
Surg 128:933-40, 2004
2. Chen F, et al. Prognositc factors of pulmonary metastasectmy for osteosarcomas of the extrimities.
Eur J Cardiovasc Surg 34:1235-9, 2008
3. Satoda N, et al. Value of FOXP3 expression in peripheral blood as rejection maker after miniature
swine lung transplantation. J Heart Lung Transplant 27:1293-301, 2008
4. Date H. Diagnostic strategies for mediastinal tumors and cysts. Thorac Surg Clin 19:29-35, 2009
5. Iwakiri S, et al. Higher expression of chemokine receptor CXCR7 is linked to early and metastatic
recurrence in pathological stage I nonsamll cell lung cancer. Cancer 115:2580-93, 2009
6. Takahashi T, et al. Clinicopathologic feasures of non-small-cell lung cancer with EML4-ALK
fusion gene. Ann Surg Oncol 2009 (Epub ahead of print)
- Clinical Medicine (Core Departments) - Surgery for Sensory and Motor System
Plastic and Reconstructive Surgery
Plastic and reconstructive surgery is a specialized branch of surgery to repair deformities and defects of the integument and
underlying musculocutaneous framework. In our field, we not only conduct clinical studies for improvement of surgical
outcomes but also focus on basic research into wound healing and microcirculation of the skin and subcutaneous tissue. In
addition, we had already begun to study skin regeneration before the phrase “regenerative medicine” became popular. One of our
achievements in this area has already been commercialized. As well as skin regeneration, we have been studying regeneration of
nerve, bone, cartilage and blood vessel. We will continue to perform clinically useful research.
Shigehiko Suzuki, M.D., Ph.D.
Professor
Current research activities in our field deal with clinical
studies regarding maxillofacial surgery, microsurgery,
skin surgery and hand surgery, and basic studies
regarding regenerative medicine, wound healing,
cutaneous microcirculation and embryology.
In regenerative medicine, we first started to develop
an artificial dermis in cooperation with the Institute
for Frontier Medical Sciences. The artificial dermis
composed of collagen sponge is spontaneously
converted into a synthesized connective tissue matrix
similar to the true dermis. The present version of our
artificial dermis has been clinically used in the world.
In addition, we have developed a new artificial dermis
that can provide sustained release of cell growth factors
and an autologous cultured dermal substitute containing
autologous fibroblasts. These are now in clinical trials in
cooperation with Translational Research Center, Center
for Cell & Molecular Therapy and the department of
dermatology. Furthermore, we have been conducting
research on skin-derived precursor cells (SKPs) and
the regenerative mechanism of elastic fibers with a
view to developing an ideal cultured skin. In addition,
we have been studying preservation of the skin and
skin substitutes. As for regeneration of cartilage, we
identified progenitor cells in the ear perichondrium
and are now developing novel scaffolds for clinical
application. Furthermore, we have been engaged in
studies on regeneration of the central nervous system,
peripheral nerves, cartilage, bone and micro vessels.
In wound healing, we are putting a great deal of
effort into elucidating the origins of keloid tissue
and hypertrophic scars and developing fundamental
treatments for these problems. In addition, we have
been engaged in preparing iPS cells to clarify the
pathogenesis of neurodegenerative and cutaneous
diseases in collaboration with CiRA (Center for iPS
Cell Research and Application) and the department of
neurology.
Such basic research is closely related to clinical
applications. We regard a clinically useful study as
highly important in our field and we are training
young researchers to have both scientific and clinical
perspectives and to aim at performing creative studies.
Plastic and Reconstructive Surgery
Professor : Shigehiko Suzuki
Senior
Lecturer : Katsuya Kawai, Motoko Naitoh,
Naoki Morimoto
Assistant
Professor : Toshihiro Ishiko, Katsuhiro Yoshikawa
TEL
: +81-75-751-3613
FAX
: +81-75-751-4340
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~keisei/
Kyoto University
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❶ Immunohistochemical analysis of elastic
fiber components in normal skin tissues (a)
and keloids (b).
❷ Skin-derived precursor cells (SKPs), which
are multipotent progenitor cells, have been
isolated from adult human dermis.
❸ Instructors and graduate students of our
department.
❹ Tissue engineered cartilage using a novel
scaffold (a) and its microscopic appearance
(b).
❺ Preparing autologous cultured dermis for
clinical trial in Cell Processing Center.
❻ Prepared autologous cultured dermis.
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Recent Publications
1. Morimoto,N.,Takemoto,S.,Kanda,N.,Ayvazyan,A.,Taira,T.,Suzuki,S.:The Utilization of animal
product-free media and autologous serum in an autologous dermal substitute culture. J Surg Res. 6
Fed 2010. [Epub ahead of print]
2. Ikeda, M., Naitoh, M., Kubota, H., Ishiko, T., Yoshikawa, K., Yamawaki, S., Kurokawa, M.,
Utani, A., Nakamura, T., Nagata, K., Suzuki, S.: Elastic fiber assembly is disrupted by excessive
accumulation of chondroitin sulfate in the human dermal fibrotic disease, keloids. Biochem. Bioph.
Res. Co. 390: 1221-1228, 2009.
3. Takemoto, S., Morimoto, N., Kimura, Y., Taira, T., Kitagawa, T., Tomihata, K., Tabata, Y., Suzuki,
S.: Preparation of collagen/gelatin sponge scaffold for sustained release of bFGF. Tissue Eng. 14:
1629-1638, 2008.
4. Kawazoe, T., Kim, H., Tsuji, Y., Morimoto, N., Hyon, S.H., Suzuki, S.: Green tea polyphenols
affect skin preservation in rats and improve the rate of skin grafts. Cell Transplantation 17: 203-209,
2008.
5. Morimoto, N., Takemoto, S., Kawazoe, T., Tomihata, Taira, T., Suzuki, S: In vivo culturing of a
bilayered dermal substitute with adipo-stromal Cells. J Surg Res. 146: 246-253, 2008.
- Clinical Medicine (Core Departments) - Surgery for Sensory and Motor Systems
Ophthalmology and Visual Sciences
Vision is a very important function for human life. The process of vision is very complicated that requires numerous components
of eye and brain work together. Our focus in research is to clarify the mechanism of various vision threatening eye diseases and
to develop new therapeutic approaches for them. To harmonize the ideas from clinics with good quality research, students must
tackle not only in research but also in clinical works. You are qualified to join our department if you have a desire to see the
details of eye diseases.
Nagahisa Yoshimura, M.D., Ph.D.
Professor
Everything related to vision is theme in our department.
Vision is a very important function for human life and
our interests of research is to understand underlying
mechanisms of ocular diseases and the abnormalities
that lead to severe visual loss. Our mission is to carry out
high-grade laboratory research through observation and
knowledge that can be obtained in the clinics.
Eye is a very small organ with the size of around 25mm
in diameter. However, the structure and function of the
eye is very complicated and many of the pathogenesis
of ocular diseases has not been clarified yet. Because
of the complexity, eye research requires many kinds
of knowledge including not only vascular biology,
neural cell biology, molecular cell biology, embryology,
anatomy, genetics, but engineering, physics and
electrophysiology. It is very exciting to put these
knowledge and ideas together to precede eye research.
One of the main interests in our laboratory are
chorioretinal diseases. On-going projects now are to
figure out the detailed mechanism in the development
of vascular diseases including age-related macular
degeneration and diabetic retinopathy, and retinal
vascular regeneration or targeted gene therapy using
bone marrow progenitor cells, and an alternate approach
to identifying potential therapeutic avenues to treating
diseases for which there are currently no effective
treatments including retinal degenerative diseases.
With industrial partners, recently, we have developed
new-generation optical coherence tomography
(OCT) and now vigorously working to elucidate the
pathophysiology of various chorioretinal diseases with
the use of new-generation OCT.
It s not easy to do research and clinical work
simultaneously, however, we believe that there is
something important for clinicians that can be obtained
only though intensive research experience. We hope you
will join us and share the excitement of eye research.
Ophthalmology and Visual Sciences
Professor : Nagahisa Yoshimura
Associate
Professor : Masanori Hangai
Senior
Lecturer : Kazuaki Miyamoto, Akitaka Tsujikawa,
Atsushi Otani
Assistant
Professor : Atsushi Nonaka, Kenji Yamashiro,
Sotaro Ooto, Tadamichi Akagi,
Tomoaki Murakami, Hanako Ikeda,
Akio Oishi, Akihito Uji
TEL
: +81-75-751-3248
FAX
: +81-75-752-0933
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~ganka/
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❶ High-resolution imaging of
t h e p h o t o r e c e p t o r l aye r u s i n g
adaptive optics scanning laser
ophthalmoscopy
❷ Spectral-domain optical coherence
tomography (SD-OCT) images
of retinal edema associated with
branch retinal vein occlusion (Ref.2)
❸ Color-coded maps of scans by which
to measure the total retinal volume
obtained by SD-OCT in the eye of a
patient with glaucoma (Ref.3)
❹ Time-lapse imaging of retinal
angiogenesis (Ref.4)
❺ Staffs
Recent Publications
1. Ooto S, Hangai M, Sakamoto A, Tsujikawa A, Yamashiro K, Ojima Y, Yamada Y, Mukai
H, Oshima S, Inoue T, Yoshimura N. High-resolution imaging of resolved central serous
chorioretinopathy using adaptive optics scanning laser ophthalmoscopy. Ophthalmology 117:
1800-1809, 2010
2. Tsujikawa A, Sakamoto A, Ota M, Kotera Y, Oh H, Miyamoto K, Kita M, Yoshimura N. Serous
retinal detachment associated with retinal vein occlusion. Am J Ophthalmol 149: 291-301, 2010
3. Mori S, Hangai M, Sakamoto A, Yoshimura N. Spectral-domain optical coherence tomography
measurement of macular volume for diagnosing glaucoma. J Glaucoma 19: 528-534, 2010
4. Unoki N, Murakami T, Ogino K, Nukada M, Yoshimura N. Time-lapse imaging of retinal
angiogenesis reveals decreased development and progression of neovascular sprouting treated with
anecortave desacetate. Invest Ophthalmol Vis Sci 51: 2347-2355, 2010
5. Hayashi H, Yamashiro K, Gotoh N, Nakanishi H, Nakata I, Tsujikawa A, Otani A, Saito M, Iida T,
Matsuo K, Tajima K, Yamada R, Yoshimura N. CFH and ARMS2 variations in age-related macular
degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation. Invest
Ophthalmol Vis Sci 51: 5914-5919, 2010
Otolaryngology-Head and Neck Surgery
Otolaryngology - Head and Neck Surgery treats all disorders in the head and neck field. Therefore we treat the largest number
of diseases in the clinical departments. Among diverse diseases, disorders of sensory organs (auditory, vestibular, olfactory,
and gustatory) are characteristic of our specialty. The most important problem to overcome is the deafness due to the cochlear
hair cell damages. We are mainly working on this project using the methods of regenerative medicine. At the same time, we are
working on the project for the regeneration of several organs such as mastoid mucosa, vocal fold, trachea, and recurrent laryngeal
nerve, for functional recovery after the deficit by surgery. Clinical application for the novel inner ear treatment using inner ear
drug delivery system and for the regeneration of the ear drum and atrophied vocal folds has been started. Another project is to
elucidate the central mechanisms of human auditory system using functional brain imaging (MEG, fMRI, and PET).
Juichi Ito, M.D., Ph.D.
Professor
■Regeneration of inner ear
Once damaged, inner ear sensory cells never regenerate
and their function do not recover. The purpose of
our study is to overcome this difficulty and realize
functional regeneration of inner ear. The 43rd Erwin von
Bälz prize was awarded to this work.
We have been addressing this difficulty using following
approaches.
1. Stem cell transplantation
We transplant the multipotent stem cells, such as ES
cells, iPS cells, bone marrow stromal cells, adipose
stem cells etc., into inner ear. Some of grafted cells
survived and differentiated into inner ear cells, and
partial functional recovery was observed. Our cell
transplantation technique is widely highly respected in
the field of inner ear research.
2. Mechanisms of hearing impairment and the
development of the new treatment
Several genes that play important roles in the
development and function of inner ear has been
identified. We investigate the mechanisms of hearing
impairment using the knockout mice and model animals
to develop the therapeutic application. By manipulating
related genes, we successfully induced proliferation
of supporting cells that do not usually happen in
the inner ear of adult mammals. We also investigate
the therapeutic potentials of growth factors and low
molecular weight agents for the treatment of hearing.
3. Therapeutic application by inner ear drug delivery
system (DDS)
Using the drug delivery system, we locally apply the
trophic factors and therapeutic drugs into the inner
ear. This method enables application of drugs without
systemic side effects. We have developed the inner ear
DDS and conducted the clinical trial using the local
application of insulin-like growth factor 1 (IGF-1). The
next phase clinical trial is in preparation.
■Regeneration of middle ear, trachea, and larynx
We study the way of regeneration of several other organs
in the head and neck using the in situ tissue engineering
techniques. Transplantation of scaffolds with stem cells
enabled the regeneration of larynx, trachea, recurrent
laryngeal nerve, and middle ear mucosa.
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❶ Neurally induced ES and iPS cells for transplantation into inner ear
❷ Proliferation of supporting cells were successfully induced by gene manipulation
❸ Surface image of Cochlear outer hair cells
❹ Regeneration of an ear drum using bFGF spongel
❺ Regeneration of the vocal fold using acellular extracellular matrix
❻ Members of inner ear regeneration research
❼ Members of regeneration research of middle ear, traceha and larynx
Recent Publications
Otolaryngology-Head and Neck Surgery
Professor : Juichi Ito
Senior
Lecturer : Shigeru Hirano, Takayuki Nakagawa
Assistant
Professor : Ichiro Tateya, Akiko Taura,
Harukazu Hiraumi, Tatsunori Sakamoto,
Norio Yamamoto, Morimasa Kitamura,
Shin-ichiro Kitajiri
TEL
: +81-75-751-3346
FAX
: +81-75-751-7225
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~ent/
Kyoto University
1. Horie RT, Sakamoto T, Nakagawa T, Ishihara T, Higaki M, Ito J. Stealth-nanoparticle strategy
for enhancing the efficacy of steroids in mice with noise-induced hearing loss. Nanomedicine
(London) 5:1331-1340, 2010.
2. Nakagawa T, Sakamoto T, Hiraumi H, Kikkawa YS, Yamamoto N, Hamaguchi K, Ono K,
Yamamoto M, Tabata Y, Teramukai S, Tanaka S, Tada H, Onodera R, Yonezawa A, Inui K, Ito J.
Topical insulin-like growth factor-1 treatment using gelatin hydrogels for glucocorticoid-resistant
sudden sensorineural hearing loss: a prospective clinical trial. BMC Med 8:76, 2010.
3. Kitajiri S, Sakamoto T, Belyantseva I, Goodyear R, Stepanyan R, Fujiwara I, Bird J, Riazuddin
Sa, Riazuddin Sh, Ahmed Z, Hinshaw J, Sellers J, Bartles J, Hammer J, Richardson G, Griffith
A, Frolenkov G, Friedman T Actin-bundling protein TRIOBP forms resilient rootlets of hair cell
stereocilia essential for hearing Cell. 2010 May 28;141(5):786-98.
4. Kishimoto Y, Hirano S, Kitani Y, et al. Chronic vocal fold scar restoration with hepatocyte growth
factor. Laryngoscope 2010;120:108-113.
5. Yamashita M, Kanemaru S, Hirano S, et al. Glottal reconstruction with a tissue engineering
technique using polypropylene mesh: A canine experiment. Ann Otol Rhinol Laryngol
2010;119:110-117.
Orthopaedic and Musculoskeletal Surgery
We, orthopaedic surgeons, treat patients who suffer diseases and injuries in the musculo-skeletal system. Most of the people
experience knee or shoulder pain and low back pain in a lifetime. Femoral or vertebral fracture is the second popular cause that
leads the elderly people to become bedridden. We believe that overcoming functional disability of the musculo-skeletal system
contribute not only to the happiness of an individual patient but also to the welfare of our whole society. The first decade in
the 21st century was the “Bone and Joint Decade”, in which the World Health Organization (WHO) promoted the world-wide
improvement in the treatment of the musculo-skeletal disorders. We hope that all people can mobilize their healthy body without
difficulties through their life.
Takashi Nakamura, MD, D.M.Sc.
Professor
Clinical and basic researches are carried out intensively and
vigorously in each group of specialists. We deal with many
joint disease including hip joint diseases (osteoarthritis of the
hip, avascular necrosis of the femoral head, etc), knee joint
diseases (osteoarthritis of the knee, ligament injury, meniscal
injury, etc), and other joint disease, rheumatoid diseases
like rheumatoid arthritis. We also treat spinal diseases (disc
herniation, ossification of the posterior longitudinal ligament,
spinal tumors, etc), bone and soft tissue tumors (osteosarcoma,
liposarcoma, etc), disorders in the upper extremity (amputated
fingers, peripheral nerve palsy, etc), and so forth. Our
department consists of 6 groups; hip surgery, sports medicine
and knee/shoulder surgery, rheumatology, spine surgery,
musculo-skeltal tumor surgery, and hand surgery. Each group
has clinical conference and/or journal club at least once a week,
where the surgeons heighten and refresh their clinical and
surgical skills. We also try frontier diagnosis and treatment as
members of world leading university.
We are also doing basic research working with postgraduate students and clinical fellows. Skeletal formation/
functional regulation group is focusing on genome-wide and
systemic analyses of gene and protein expression, function
in skeletogenesis and bone and cartilage metabolism using
molecular biological, biochemical, and mouse genetics
approaches. Biomaterial group has developed many bioactive
implants, some of which have been applied clinically. Recently
good osteoconductive and osteoinductive titanium has been
developed. Using this material, a new spinal fusion cage was
made and used in patients as a clinical trial, with an excellent
result. Tumor group is researching on a molecular mechanism
of generation of bone and soft tissue tumor and its application
to clinical cases. Application of bone marrow stromal cells
to necrotic lesion of femoral head or carpal bone is under
clinical research, collaborated with Institute for Frontier
Medical Science. Cartilage metabolism/rheumatology group is
experimentally investigating the mechanism of joint destruction
in osteoarthritis and rheumatoid arthritis, leading to future
cartilage repair. Sports medicine and knee/shoulder surgery
group is developing imaging systems in order to evaluate
physical and structural properties of the cartilage for clinical
applications. Peripheral nerve group is working on the nerve
regeneration, once thought impossible, trying to apply the
method for treating nerve degeneration and injury.
Orthopaedic and Musculoskeletal Surgery
Professor : Takashi Nakamura
Associate
Professor : Masashi Neo, Haruhiko Akiyama
Senior
Lecturer : Tomitaka Nakayama,
Masahiko Kobayashi
Assistant
Professor : Hiromu Ito, Shunsuke Fujibayashi,
Takeharu Nakamata, Takeshi Okamoto,
Hiroyuki Yoshitomi, Tadashi Goto,
Mitsuru Takemoto, Koji Yamamoto
TEL
: +81-75-751-3652
FAX
: +81-75-751-8409
e-mail
: [email protected]
URL
~seikeigeka/
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❶ Navigation system is used in a difficult operation in spine surgery as well as artificial joint
surgery. (Reference1)
❷ Newly developed cementless total hip joint system (left) and canine spinal fusion using
bioactive porous titanium (right). (Reference2, 3)
❸ Clinical application of bone marrow stromal cell to necrotic lesion of femoral head or
hand. (left: treatment, right: non-treatment) (Reference4)
❹ Skeletogenesis and bone and cartilage metabolism by molecular biological, biochemical,
and mouse genetics approaches. (Reference5)
❺ Staff of orthopedic surgery
Recent Publications
1. Ikeguchi R, Kakinoki R, Aoyama T, Shibata KR, Otsuka S, Fukiage K, Nishijo K, Ishibe T,
Shima Y, Otsuki B, Azuma T, Tsutsumi S, Nakayama T, Otsuka T, Nakamura T, Toguchida
J,:Regenerartion of osteonecrosis of canine scapho-lunate using marrow stromal cells: possible
therapeutic approach for Kienbock disease:Cell Transplant:15,5: 411-22:2006
2. Takemoto M, Fujibayashi S, Neo M, So K, Akiyama N, Matsushita T, Kokubo T, Nakamura T,:A
porous bioactive titanium implant for spinal interbody fusion: an experimental study using a canine
model:J Neurosurg Spine:4:435-43:2007
3. Kimura H, Kwan KM, Zhang Z, Deng JM, Darnay BG, Behringer RR, Nakamura T,
Crombrugghe B, Akiyama H,:Cthrc1 is a positive regulator of osteoblastic bone formation:PLoS
ONE:3,9:e3174:2008
4. Miyata M, Neo M, Fujibayashi S, Ito H, Takemoto M, Nakamura T,:O-C2 angle as a predictor of
dyspnea and/or dysphagia after occipitocervical fusion:Spine (Phila Pa 1976) :34,2:184-8:2009
5. Kitaori T, Ito H, Schwarz EM, Tsutsumi R, Yoshitomi H, Oishi S, Nakano M, Fujii N, Nagasawa
T, Nakamura T, :Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment
of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model:Arthritis
Rheum:60,3:813-23:2009
6. Kawanabe K, Ise K, Goto K, Akiyama H, Nakamura T, Kaneuji A, Sugimori T, Matsumoto T,:A
new cementless total hip arthroplasty with bioactive titanium porous-coating by alkaline and heat
treatment: average 4.8-year results:J Biomed Mater Res B Appl Biomater:90,1:476-81:2009
Department of Oral and Maxillofacial Surgery is committed with academic oral surgeon aiming to progress the clinical care,
education, and scientific research. Our mission is to advance the modern diagnosis and treatment for dent-maxillofacial, oral
and craniofacial disorders through innovative basic and clinical research. Based on Kyoto University’s highest intellectual and
physical resources, we are maintaining the top level of patient’s care, residency and postgraduate education program, and frontier
research.
Kazuhisa Bessho, D.D.S.,D.M.Sc.
Professor
The current researches in our department are as follows.
Our major interest is to clarify the mechanisms of the onset
of temporomandibular joint disorders (TMDs), especially
"closed lock". In previous studies, our research unit has
evaluated histopathologic and biochemical alterations of
temporomandibular arthritis induced by mechanical loading
in rabbits (arthritis animal models), because excessive loads
on the glenoid fossa is thought one of the significant causes of
TMDs. Also our research unit has analyzed concentration of
proteins and cytokines in the synovial fluids of TMD patients.
Now we have interest in methodologies of mass spectrometric
analysis of hyaluronic acid in synovial fluids. Our research
unit is analyzing normal and abnormal jaw function through
refined recordings of muscle activity and jaw movement in
3 dimensional magnetic resonance imaging (MRI) and high
speed MRI (HASTE method: figure ) for studying the detailed
functions of the jaw muscles. These same methodologies are
being applied to the study of jaw function in TMD patients
to identify differences between TMD patients and normal
persons. We think the outcomes from these studies should lead
to a reduction of the burden that TMD causes on the medical
practice. Uterine sensitization associated gene-1 (USAG-1) is
a BMP antagonist that functions in the local regulation of BMP
mediated signal transduction by binding and neutralizing BMP
activities, and also modulates Wnt signaling . We previously
reported that USAG-1 deficient mice have supernumerary
teeth. The supernumerary maxillary incisor appears to form as
a result of the successive development of the rudimentary upper
incisor. USAG-1 abrogation rescued apoptotic elimination of
odontogenic mesenchymal cells. We confirmed that BMPs
were expressed in both the epithelium and mesenchyme of
the rudimentary incisor at E14 and E15. BMP signaling in
the rudimentary maxillary incisor, assessed by expressions
of Msx1 and Dlx2 and the phosphorylation of Smad protein,
was significantly enhanced. Inhibition of BMP signaling
rescues supernumerary tooth formation in E15 incisor explant
culture. Based upon these results, we conclude that enhanced
BMP signaling results in supernumerary teeth in the USAG1 deficient mouse model. We constructed a BMP-2-expressing
adenoviral vector with high efficiency and succeeded gene
transfer by electroporation and sonoporation with a BMP-2expressing plasmid vector. These bone regeneration methods
may be useful in clinic. The pluripotential cells isolated from
the pulp of human teeth and expanded in vitro, differentiated
into osteoblasts, chondrocytes and adipocytes. We research
about biomaterials and bone reconstruction using bone
morphogenetic protein expressing vector. And we examine
interactions between osteoinduction and chemicals. On the
other hand, we research and develop new diagnosis devices,
operation devices and dental implant in cooperation with
Faculty of Engineering and enterprises.
Professor : Kazuhisa Bessho
Associate
Professor : Kazuma Fujimura
Senior
Lecturer : Katsu Takahashi, Junya Sonobe
Assistant
Professor : Kazuhisa Goto, Masashi Yamori,
Hiromitsu Yamamoto
TEL
: +81-75-751-3401
FAX
: +81-75-761-9732
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/%7E
oral_surg/Oral_Surg_index.html
Kyoto University
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❶ High speed MRI (HASTE)
Left: Anterior displacement
of disc without reduction
❷ Osteoinduction by bone
mor phogenetic protein
using transcutaneous
sonoporation.
❸ Supernumerary maxillary
incisor in USAG-1 deficient
mouse
❹ Osteoinduction in the calf
muscle of rat by bone
morphogenetic protein-2expressing recombinant
adenoviral vector.
❺ The research on the links
between oral health and
general health
❻ Staffs
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Recent Publications
1. Takafuji H, Suzuki T, Okubo Y, Fujimura K, Bessho K. Regeneration of articular cartilage defects
in the temporomandibular joint of rabbits by fibroblast growth factor-2.Int J Oral Maxillofac Surg.
36, 934-937, 2007.
2. Takahashi, K., Sakata, T., Murashima-Suginami, A., Tsukamoto, H., Kiso, H., Bessho, K. Tooth
regeneration: Potential for stimulation of the formation of a third dentition by one gene, Current
Topics in Genetics, 3, 77-82, 2008
3. Osawa K, Okubo Y, Nakao K, Koyama N, Bessho K. Osteoinduction by repeat plasmid injection
of human bone morphogenetic protein-2. J Gene Med. 12, 937-944, 2010
4. Kaihara S, Bessho K, Okubo Y, Sonobe J, Kawai M, Iizuka T. Simple and effective osteoinductive
gene therapy by local injection of a bone morphogenetic -2-expressing recombinant adenoviral
vector and FK506 mixture in rats. Gene Therapy. 11:439-447, 2004
5. Yamori M, Yoshida M, Watanabe T, Shirai Y, Iizuka T, Kita T, Wakatsuki Y Antigenic activation of
Th1 cells in the gastric mucosa enhance dysregulated apoptosis and turnover of the epithelial cells.
Biochem Biophys Res Commun. 316:1015-1021, 2004
- Clinical Medicine (Core Departments) - Medical Genetics
Few areas of medicine remain unaffected by the rapid developments in molecular genetics that have taken place over recent
years. Not only the classic Mendelian disorders, but also diseases of complex and multifactorial etiology are now susceptible
to investigation at the molecular level. Moreover, gene therapies are expected to become important therapeutic modalities in
the 21st century. To apply molecular medicine to the clinics, however, there are still many problems. We need hard-working,
motivated individuals to work with us to resolve them.
Jun Fujita, M.D., Ph.D.
Professor
Hepatocellular carcinoma (HCC) is a common
and aggressive malignant tumor with especially
high prevalence in Asia and Africa. Many are
diagnosed with advanced HCC and have little chance
of survival. To improve diagnosis and identify
therapeutic targets for the treatment of HCC patients,
we have isolated several genes overexpressed in
HCC such as novel genes gankyrin and HSCO. Since
gankyrin was overexpressed in all HCC analyzed, we
have been developing therapeutic agents based on its
structure or functions.
Compared to bacteria and plants, the cold shock
response has attracted little attention in mammals.
Although previous studies have mostly dealt with
temperatures below 20°C, we are interested in mild
cold (32°C), and have shown that it can change the
cell's response to subsequent stresses. Furthermore,
we have identified the first cold shock protein, Cirp,
in mammalian cells at 32°C. We have identified
more mammalian cold shock proteins, and have
been clarifying the regulatory mechanisms of mildcold response. Mammalian cells are metabolically
active and respond to stresses at 32°C with strategies
different from those at 37°C.
Genetic counseling has been impacted by the rapid
increase in information. To gain easy access to the
expanding and useful clinical genetics resources, we
have started an internet site, “Iden-Net”. Among its
contents, most noteworthy will be the computerized
directory of Japanese laboratories performing
disease-specific DNA testing of heritable disorders
and the directory of Japanese genetic counselors.
❶ Structure of gankyrin.
Orthogonal ribbon
representations of gankyrin.
The polypeptide chain is
color-ramped from its N
terminus in blue to the C
terminus in red.
❷ Delivering polyubiquitylated
substrates to the 26S
proteasome.
Gankyrin probably delivers
ubiquitylated p53 to the
proteasome by binding
to MDM2 as well as the
S 6 b s u bu n i t o f t h e 2 6 S
proteasome.
❸ Te m p e ra t u r e - d e p e n d e n t
expression of cirp mRNA in
BALB/3T3 cells.
❹ Members of the laboratory.
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Recent Publications
Professor : Jun FUJITA
Associate
Professor : Katsuhiko ITOH
Assistant
Professor : Hiroaki HIGASHITSUJI,
Hisako HIGASHITSUJI
TEL
: +81-75-751-3751
FAX
: +81-75-751-3750
e-mail
: [email protected]
1. Higashitsuji, H., Itoh, K., Nagao, T., Dawson, S., Nonoguchi, K., Kido,T., Mayer, R.J., Arii, S.,
Fujita, J. (2000) Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrinrepeat protein overexpressed in hepatomas. Nature Med., 6, 96-99.
2. Higashitsuji, H., Higashitsuji, H., Nagao, T., Nonoguchi, K., Fujii, S.,Itoh, K., Fujita, J. (2002) A
novel protein overexpressed in hepatoma accelerates export of NF-_B from the nucleus and inhibits
p53-dependent apoptosis. Cancer Cell, 2, 333-346.
3. Higashitsuji H, Higashitsuji H, Itoh K, Sakurai T, Nagao T, Sumitomo H,Masuda T, Dawson
S, Shimada Y, Mayer RJ, Fujita J.(2005) The oncoprotein gankyrin binds to MDM2/HDM2,
enhancing ubiquitylation and degradation of p53. Cancer Cell, 8, 75-87.
4. Higashitsuji, H., Higashitsuji ,H., Masuda, T., Liu, Y., Itoh, K.,Fujita, J. (2007) Enhanced
deacetylation of p53 by the anti-apoptotic protein HSCO in association with HDAC1. J. Biol.
Chem., 282, 13716-13725.
5. Fujita, J. (2008) Gankyrin. in Encyclopedia of Cancer, 2nd ed. Schwab M(ed), pp1205-1207,
Springer, Berlin.
- Clinical Medicine (Core Departments) - Clinical Neuroscience
Neurology
Department of Neurology have served as an academic research center by educating students, residents, and staff towards
professional values in neurosciences; neuropathology, neurochemistry, molecular neurobiology, and neurophysiology using
molecular biology, molecular genetics, developmental engineering, pharmacology, electrophysiology, histology, and/or system
brain science to achieve novel and efficient therapies for intractable neurological diseases.
Ryosuke Takahashi, M.D. Ph.D.
Professor
❶
●
❷
●
Department of Neurology consists of 4 laboratories.
In Neuropathology lab, we examine human
autopsy brains in clinico-pathological conference,
and further study with immunohistochemistry
and neurochemical methods. Using geneticallymodulated animals, we are doing research work on
the pathogenesis and new therapeutic strategies for
stroke and dementia, and neurodegenerative diseases
(Figure 1).
In Neurochemistry lab, we study the molecular
mechanism of neuronal death in neurodegenerative
disorders including Alzheimer’s disease, Parkinson’s
disease and amyotrophic lateral sclerosis (ALS),
and are trying to develop novel therapy for the
diseases. For example we have revealed the nicotinic
receptor-mediated neuroprotective cascade (Figure
2). Moreover, we study proteomics to investigate
the pathogenesis and develop diagnostic methods in
neurodegenerative disorders.
Molecular Neurobiology lab aims to provide
novel preventive/therapeutic approaches towards
sporadic Parkinson’s disease and ALS based on
recent findings that misfolded proteins cause
neurodegeneration either in familial Parkinson’s
disease or familial ALS (Figure 3).
In Neurophysiology lab, we have aimed at
elucidating the pathophysiology of the diseases of
the central nervous systems involving the neuronal
circuitry and functional organization such as
epilepsy, movement disorders and higher cortical
dysfunctions, and at promoting the new treatment
approaches. We also have clarified the mechanism
of higher cortical functions in humans such as motor
control, language and sensory perception, all of
which are always related to the relevant diseases
(Figure 4).
❶ Neuropathology lab accumulated 360 brains with a variety of neurological diseases.
For education, we provide students and residents
These disease include cerebrovascular diseases, infection, tumor, neurodegenerative
with organized, educational course of researches.
and demyelinating diseases. The brains are subjected to clinicopathological conference
and examination with immunohistochemical and neurochemical methods.
❷ Nicotinic receptor-mediated neuroprotection against apoptosis.
Neurology
Professor : Ryosuke Takahashi
Associate
Professor : Akio Ikeda
Senior
Lecturer : Hidefumi Ito
Assistant
Professor : Riki Matsumoto, Kengo Uemura,
Masafumi Ihara, Makio Takahashi,
Hirofumi Yamashita
TEL
: +81-75-751-4397
FAX
: +81-75-761-9780
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/%7
Eneurology/
Kyoto University
Recent Publications
1. Imai, Y., Soda, M., Inoue, H., Hattori, N., Mizuno, Y. and Takahashi, R. An unfolded putative
membrane transmembrane olypeptide, which can lead to endoplasmic reticulum stress, is a
substrate of Parkin. Cell 105, 891-902, 2001.
2. Kinoshita, M., Ikeda, A., Matsumoto, R., Begum, T., Usui, K., Yamamoto, J., Matsuhashi, M.,
Takayama, M., Mikuni, N., Takahashi, J., Miyamoto, S., and Shibasaki, H. Electric stimulation on
human cortex suppresses fast cortical activity and epileptic spikes. Epilepsia 45: 787-791, 2004.
Neurosurgery
As the advance of neuroscience, neurosurgery has developed into a division of neuroscience from the specialized field
concerned with the diagnosis and treatment of disorders or injuries in the brain, spinal cord or peripheral nerves. Our department
is characterized as high activity in clinical science, a faculty to develop innovative treatments based on neuroscience, and
establishments of medical evidence for the management of nervous system and neurovascular disorders. We also collaborate
with basic research laboratories and apply its results into the clinical field. This scientific approach is also of great advantage to
the education system in neurosurgery.
Susumu Miyamoto, M.D., Ph.D.
Professor
Clinical Research
Our department plays a major role in the nationwide clinical
studies of moyamoya disease, unruptured cerebral aneurysm,
hemodynamic brain ischemia and brain tumors. To preserve
the patient’s brain function, we advance the surgical technique
and operation system using awake-craniotomy and functional
brain mapping. Our clinical research has developed on the base
that we are in possession of microsurgical training system,
abundant clinical experience and many experts in neurosurgical
subspecialty.
Basic Research
In the neurovascular laboratory, we investigate susceptible
genes for the familial intracranial aneurysms, arteriovenous
malformation and moyamoya disease. Using animal models
of cerebral aneurysms, we have shown that cerebral aneurysm
formation is based on the chronic vascular inflammation.
Recently, the studies of risk factor for ischemic stroke and
the instrument to evaluate arteriosclerosis noninvasively have
launched. In the brain tumor laboratory, we are currently
focusing to determine the molecular mechanism of glioma
growth and invasion using in-vivo imaging system with twophoton microscope, epigenetic regulation of brain tumor stem
cell, and molecular diagnosis of glioma. We also try to establish
oncolytic therapy with vaccinia virus. In the brain functional
laboratory, we develop methodology for human brain imaging
with high-resolution 3-tesla MRI and magnetoencephalography
(MEG) and intraoperative brain functional mapping and
monitoring. In the neuronal regeneration laboratory, we
challenge to establish the regeneration treatment for Parkinson
disease and brain ischemia using ES cells and iPS cells. We also
study the bHLH factor regulation in pituitary gland generation
and new artificial materials useful for neurosurgical treatments.
Education
Our department has improved the education system for young
neurosurgeon by collaborating with the related hospitals.
Our aim is that a trainee rapidly acquires the skill necessary
to microsurgery and endovascular treatment through plenty
of clinical experience and skill training in the laboratory.
Furthermore, there are opportunities to learn techniques of
neurosurgical subspecialty in the related hospital, such as spine
surgery, pediatric neurosurgery and endovascular surgery. In the
Ph.D. course, the student attends to basic research applicable
to neurosurgical fields, which will add his/her ability to think
scientifically at clinical work. All young neurosurgeon also
has a chance to receive their skill training in the domestic and
foreign institutes. The goal is that we provide a neurosurgeon
with high-level skill as well as makings of a leader in
neurosurgical field.
Neurosurgery
Professor : Susumu Miyamoto
Senior
Lecturer : Jun Takahashi, Taketo Hatano
Assistant
Professor : Yoshiki Arakawa, Akira Ishii,
Masanobu Okauchi,
Kazumichi Yoshida, Masato Hojo
TEL
: +81-75-751-3450
FAX
: +81-75-753-9501
e-mail
: [email protected]
URL
~neurosurg/index.html
❶
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❷
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❹
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❶ Maximum flow reduction (MFR) strategy for large thrombosed aneurysms.
❷ Brain functional study with high-resolution 3-tesla MRI
❸ Clinical application of the artificial dura mater made of absorptive material.
❹ Oncolytic therapy with vaccinia virus: vaccinia virus (green) and actin filament (red).
❺ Induction of neuronal cells from ES cells.
Recent Publications
1. Iihara K, Murao K, Yamada N, Takahashi JC, Nakajima N, Satow T, Hishikawa T, Nagata I,
Miyamoto S. Growth potential and response to multimodality treatment of partially thrombosed
large or giant aneurysms in the posterior circulation. Neurosurgery 2008; 63(5):832-42.
2. Ogawa A, Mori E, Minematsu K, Taki W, Takahashi A, Nemoto S, Miyamoto S, Sasaki M, Inoue
T; MELT Japan Study Group. Randomized trial of intraarterial infusion of urokinase within 6 hours
of middle cerebral artery stroke: the middle cerebral artery embolism local fibrinolytic intervention
trial (MELT) Japan. Stroke. 2007;38(10):2633-9.
3. Mikuni N, Okada T, Nishida N, Taki J, Enatsu R, Ikeda A, Miki Y, Hanakawa T, Fukuyama
H, Hashimoto N. Comparison between motor evoked potential recording and fiber tracking for
estimating pyramidal tracts near brain tumors. J Neurosurg. 2007; 106(1):128-33.
4. Hayase M, Kitada M, Wakao S, Itokazu Y, Nozaki K, Hashimoto N, Takagi Y, Dezawa M.
Committed neural progenitor cells derived from genetically modified bone marrow stromal cells
ameliorate deficits in a rat model of stroke. J Cereb Blood Flow Metab. 2009.
5. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Morishita R, Hashimoto N. Reduced Collagen
Biosynthesis Is the Hallmark of Cerebral Aneurysm. Contribution of Interleukin-1{beta} and
Nuclear Factor-{kappa}B. Arterioscler Thromb Vasc Biol. 2009
6. Hirata E, Arakawa Y, Shirahata M, Yamaguchi M, Kishi Y, Okada T, Takahashi JA, Matsuda M,
Hashimoto N. Endogenous tenascin-C enhances glioblastoma invasion with reactive change of
surrounding brain tissue. Cancer Sci. 2009
Psychiatry
The Department of Psychiatry was established in September 1902, just 100 years ago. From then onward, our Department
has continued to play an important role as a clinical research center for psychiatry in Japan, in particular, in the realms of
psychopathology, neuropsychology, neuropathology, child and forensic psychiatry. We will uphold this tradition and continue
to go ever further. However, psychiatry is also related to the recently rapid developments in brain science. Currently, various
techniques from brain imaging to a gene analysis are being used in psychiatric research. We will actively conduct these
biological studies in order to elucidate the etiology or pathogenesis of psychoses and find new treatment techniques.
Toshiya Murai
Professor
By applying neurobiological as well as psychosocial
approaches flexibly, we aim to achieve a multifaceted understanding of psychiatric disorders.
1)Neuroimaging
Impairment of social cognition, decision
making, and social behaviors are common in
various neuropsychiatric conditions. Multimodal
neuroimaging, including functional MRI and high
resolution gray and white matter imaging, is applied
to elucidate the neural correlates of these processes.
2) Psychopathology
Psychopathology, which attempts to directly
understand the psychology underlying mental
phenomena, is one of the essential approaches to
investigation of psychiatric diseases. Especially, we
focus on eating disorders, dissociative disorders and
psychiatric aspects of epilepsy. Psychiatric issues of
patients and donors of living organ transplantation
are also studied.
3)Neuropsychology
I n c o l l a b o r a t i o n w i t h b r a i n s u rg e o n s a n d
occupational and speech therapists, neural correlates
of cognitive and behavioral sequelae after brain
damage are investigated. Especially, we attempt to
elucidate the mechanisms and possible therapeutic
approaches for alterations of social behaviors after
traumatic brain injury
4) Child and Adolescent Psychiatry
We are currently focusing on the following themes on
developmental disorders in children and adolescents:
variability of diagnostic assessments; relationships
between phenotype and neurocognitive functions;
effectiveness of each intervention; and factors
predicting outcome.
5)Forensic psychiatry
We tackle issues of criminal responsibility and civil
competency of individuals with mental disorders.
Especially, biological and psychosocial mechanisms
of violence as well as the predictability of a return
to criminal behavior after treatment or release from
incarceration are investigated by combining multidisciplinary approaches.
Psychiatry
Professor : Toshiya Murai
Senior
Lecturer : Shun'ichi Noma, Takashi Okada,
Hidehiko Takahashi
Clinical
Lecturer : Kenjiro Fukao
Assistant
Professor : Akira Oshita, Taro Suwa,
Nobuyuki Yamasaki, Jun Miyata,
Keita Ueda, Yasuko Funabiki
TEL
: +81-75-751-3386
FAX
: +81-75-751-3246
e-mail
: [email protected]
URL
~psychiat/
Kyoto University
Recent Publications
1. Hirao K, Miyata J, Fujiwara H, Yamada M, Namiki C, Shimizu M, Sawamoto N, Fukuyama H,
Hayashi T, Murai T. Theory of mind and frontal lobe pathology in schizophrenia: A voxel-based
morphometric study. Schizophrenia Research 105:165-74, 2008.
2. Miyata J, Hirao K, Namiki C, Fujiwara H, Shimizu M, Fukuyama H, Sawamoto N, Hayashi T,
Murai T. Reduced white matter integrity correlated with cortico-subcortical gray matter deficits in
schizophrenia. Schizophrenia Research 111:78-85, 2009.
3. Ueda K, Fujiwara H, Miyata J, Hirao K, Saze T, Kawada R, Fujimoto S, Tanaka Y, Sawamoto
N, Fukuyama H, Murai T. Investigating association of brain volumes with intracranial capacity in
schizophrenia. Neuroimage 49:2503-8, 2010.
4. Noma S, Hayashi A, Uehara M, Kuwabara H, Tanaka S, Furuno Y, Ogawa K, Hayashi T.
Psychosocial predictors of psychiatric disorders after living donor liver transplantation.
International Journal of Psychiatry in Clinical Practice 12:120-126, 2008.
5. Okada T, Sato W, Kubota Y, Usui K, Inoue Y, Murai T, Hayashi T, Toichi M. Involvement of medial
temporal structures in reflexive attentional shift by gaze. Soc Cogn Affect Neurosci 3:80-88, 2008.
- Clinical Medicine (Core Departments)
Transfusion Medicine and Cell Therapy
Former department was fully restructured in 2002 as a new Department of Transfusion Medicine and Cell Therapy along with the
rapid progress of medicinal science elucidating new molecular and cellular pathophysiology of incurable diseases such as cancers. In
addition to control transfusion therapy in the hospital, we supply purified hematopoietic stem cells and relevant cells to clinical trials
for allogeneic bone marrow, peripheral blood, and cord blood transplantations. Our research and clinical goals are to develop innovative
cell therapy, regenerative therapy, and molecular target therapy for leukemias and other malignancies. Stem cell transplantation, cell and
regenerative therapy, and molecular target therapy being ultimate therapeutic approaches for incurable diseases, their establishments
(translational research) are urgently needed. To provide clinical-graded therapeutic human cells for translational trials, GMP-graded cell
processing facility (Center for Cell and Molecular Therapy: CCMT, Fig.1) has been established in 2003 next door to the Department.
Taira Maekawa, M.D., D.Med. Sci.
Therefore, the Department of Transfusion Medicine and Cell Therapy will play the pivotal role in new era for the progress of advanced
Professor
medical research and clinical trials at Kyoto University Hospital.
This department is responsible for education
concerning transfusion medicine for undergraduate
and graduate students, and also has to supervise
appropriate use of blood products for transfusion
therapy in the university hospital. In addition, to
improve the clinical outcome of hematopoietic stem
cell transplantation and cell therapy, we provide
qualified and powerful therapeutic human cells and
tissues to the clinical settings and develop novel
method to detect anti-ABO, and anti-HLA antibodies
(Fig 2). Recently we have successfully performed
allogeneic islet cell transplantation to a patient with
severe type I diabetes from a related living donor
for the first time in the world. In addition to these
cellular therapy, we have been engaged in basic
and clinical researches involving molecular target
therapy for cancer. We are now working on the
following three main projects; a) imatinib mesylate,
a competitive inhibitor of Abl tyrosine kinase, is
highly effective, but remissions induced in advanced
phase CML and Philadelphia chromosome positive
(Ph+) acute lymphoblastic leukemia tend to be
relatively short-lived mostly due to point mutations
within the Abl kinase domain. New tyrosine kinase
inhibitors have been developed to override such
resistance. We developed INNO-406, which is one
of these new compounds and phase I clinical trial
has been successfully, and has named bafetinib and
multi-kinase inhibitor, AT9283 (Fig.3) , b) RNA
interference, which has recently been introduced
into cancer therapy, is a newly discovered cellular
pathway for silencing genes at the mRNA level in
a sequence-specific manner by the introduction of
small interfering RNA (siRNA)(Fig.4), c) γδT cells
kill myeloma cells by recognizing metabolites of the
mevalonate pathway and ICAM-1 on the myeloma
cells. This suggests that patients with myeloma cells
that express high levels of ICAM-1 are suitable
for cellular immunotherapy usingγδT cells in a
clinical setting (Fig.5). We are also interested in the
transcriptional system of granulopoiesis and in the
control of GvHD using mesenchymal stem cells, and
trying to bring it into translational research. Young
investigators and graduate students with curious and
challenging mind are always very welcome (Fig.6).
Transfusion Medicine and Cell Therapy
Professor : Taira Maekawa
Senior
Lecturer : Hideyo Hirai
Assistant
Professor : Yasuo Miura
TEL
: +81-75-751-3628
+81-75-751-3630
FAX
: +81-75-751-3631
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~dtm/
index.html
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❶ Cell processing for
cultured mesenchymal
stem cells at CCMT
❷ Novel method using
surface plasmon
resonance to detect
anti-A/B antibodies
❸ News release of novel
multi-kinase inhibitor
for CML
❹ PLK-1 siRNA inhibits
progression of liver
metastasis in lung
cancers
❺gamma delta T
cells (small) attack
malignant cells (large)
❻ Colleagues of the
department
❻
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Recent Publications
1. Takeuchi M et al. (2011) Rakicidin A effectively induces apoptosis in hypoxia adapted Bcr-Abl
positive leukemic cells. Cancer Sci, in press.
2. Tanaka R et al. (2010) Activity of the multi-targeted kinase inhibitor, AT9283, in imatinib-resistant
BCR-ABL positive leukemic cells. Blood 116(12):2089-95.
3. Takeuchi M et al. (2010) Glyoxalase-I induction during hypoxia adaptation in Bcr-Abl positive
leukaemic cells. Cell Death Diff 17:1211-1220.
4. Ashihara E et al. (2010) Future Prospect of RNA interference for cancer therapies. Curr Drug
Targets. 11(3): 345-360, 2010.
5. Ashihara E et al. (2009) Beta-catenin siRNA successfully suppressed progression of multiple
myeloma in a mouse model. Clin Cancer Res, 15:2731-2738.
6. Yokota A et al (2007) INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses
the growth of Ph+ leukemia cells in the central nervous system and cyclosporine A augments its in
vivo activity. Blood, 109:306-314
7. Hirai H et al(2006) C/EBPbeta is required for emergency granulopoiesis. Nat Immunol. 7:732-739.
- Clinical Medicine (Core Departments) - Laboratory of Diagnostic Pathology
The Department of Diagnostic Pathology was established in 1980, and has long been recognized as a branch laboratory of
investigative pathology and clinical pathology. Diagnostic pathology is a clinical application of proteomics and cellular
pathology, contributing to determination of treatment strategy and evaluation of effects of treatment. In accordance with
reorganization of the departments of investigative pathology, our department is now responsible for all autopsies and education
of systemic pathology for undergraduate students as well as examination and interpretation of surgical specimens and
cytopathological specimens in Kyoto University.
Hironori Haga
Professor
Members of the department are experts in surgical
pathology of several organs and some specific
diseases. They pursue individual research projects
in close cooperation with clinicians and other
biomedical researchers. Most of our researches
are clinically oriented, and our goal is to provide
accurate and scientific diagnosis based on histology
and cytology.
Current clinical researches include 1) analysis of
allograft rejection and other complications after
organ transplantation, 2) diagnosis of rare cervical
cancers, 3) study on IgG4-related systemic diseases.
Other current and previous study included analysis
of duodenal cancer, lung cancer, bone tumors, and so
on. More basic themes are 1) elucidation of JAK2/
STAT5 pathway in development of hematologic
malignancies, 2) chimerism and senescence of
the liver allograft, and 3) treatment of mast cell
disorders. In addition to these studies initiated by
pathology members, we are involved in several
projects lead by clinicians.
Education for graduate students is combination
of research and advanced training for diagnostic
pathology. Subspecialty training for surgical
pathology or cytopathology is encouraged in
combination with basic investigative research
and/or traditional pathology study using
immunohistochemistry and in situ hybridization.
Complete in-house digital pathology database and
image analysis using virtual microcopy are also
available.
❶
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❶ Endothelial chimerism. Original
donor endothelium (green)
mixed with recipient-derived
endothelial cells (brown)
reflecting portal fibrosis and
neovessel formation.
❷ C4d-positive chronic rejection
after liver transplantation.
❸ IgG4-related lung disease
showing vasculitis with IgG4positive plasma cells.
❹ Staffs.
❹
●
Recent Publications
Professor : Hironori Haga
Associate
Professor : Yoshiki Mikami, Sachiko Minamiguchi
Senior
Lecturer : Aya Miyagawa-Hayashino
Assistant
Professor : Shinji Sumiyoshi
TEL
: +81-75-751-3488
FAX
: +81-75-751-3499
e-mail
: [email protected]
URL
~pathology/index.html
Kyoto University
1. Tsuruyama T, Nakai T, Hiratsuka T, Jin G, Nakamura T, Yoshikawa K. In vitro HIV-1 selective
integration into the target sequence and decoy-effect of the modified sequence. PLoS One.
2010;5:e13841.
2. Miyagawa-Hayashino A, Egawa H, Yorifuji T, Hasegawa M, Haga H, Tsuruyama T, Wen MC,
Sumazaki R, Manabe T, Uemoto S. Allograft steatohepatitis in progressive familial intrahepatic
cholestasis type 1 after living donor liver transplantation. Liver Transpl. 2009;15:610-8.
3. Mikami Y, Kiyokawa T, Sasajima Y, Teramoto N, Wakasa T, Wakasa K, Hata S. Reappraisal of
synchronous and multifocal mucinous lesions of the female genital tract: a close association with
gastric metaplasia. Histopathology. 2009;54:184-91.
4. Fujimoto M, Haga H, Okamoto M, Obara E, Ishihara M, Mizuta N, Nishimura K, Manabe T. EBVassociated diffuse large B-cell lymphoma arising in the chest wall with surgical mesh implant.
Pathol Int. 2008;58:668-71.
5. Yamashita K, Haga H, Kobashi Y, Miyagawa-Hayashino A, Yoshizawa A, Manabe T. Lung
involvement in IgG4-related lymphoplasmacytic vasculitis and interstitial fibrosis: report of 3 cases
and review of the literature. Am J Surg Pathol. 2008;32:1620-6.
- Clinical Medicine (Core Departments) - Medical Informatics
Medical Informatics
Medical informatics is an academic discipline seeking new informatics knowledge and technology that supports medical
effectiveness and efficacy.
Medical informatics is growing academic discipline that approaches any academic topics of medicine including basic, clinical
and community medicine and topics across their boundaries via technology and knowledge of information science.
We are expecting for prospective colleague with full of curiosity, concentration, and, most of all, flexibility to enjoy any
academic activities.
Hiroyuki Yoshihara, M.D., Ph.D.
Professor
❶
●
2) Research and Development of Tele-health environment
(fig.2)
Medical Informatics division is developing an integrated
information assistance environment “Surgical Cockpit
System” that aim at robotic tele-healthcare in future and
its technological infrastructure including application level
integrated QoS controlled communication technology.
❷
●
❶ Data Centers for accumulating
clinical infor mation are
established in each region.
Using these centers, clinical
information is shared by clinics
and hospitals. Every patient also
can refer his/her data.
❷ Surgical Cockpit System (TeleMedicine)
❸ Virtual Reality based surgical
planning and training simmulater
❹ Radiological document retrieval
system using annotation
information of schema.
1) Planning and designing toward the community healthcare
alliance. (fig.1)
According the arrival of aging society and new medical
technology, total health care expenditure is increasing
rapidly in these days. These change result in the rationing
of total health care expenditure in national budget. They
also result in increasing social pressure toward quality
healthcare and efficacy. Such change of environment
requires alliance in community to provide appropriate
healthcare services without wasting resources. Medical
informatics division, collaborating with Kyoto-fu Medical
Association, healthcare organizations in the Kyoto
Prefecture, Government of Kyoto Prefecture and Kyoto city
etc., is planning and designing toward the establishment of
community healthcare alliance consortium “MAIKO-net”.
3) Research and Development of Surgery Simulator (fig.3)
To meet the controversies to training high-tech medicine
and requirement toward patient safety, innovative
educational method to train highly technical surgical
operation combining conventional educational method
that is conducted on the job training and new information
technology is required. Medical informatics division,
applying Virtual Reality technology, developed Surgery
Simulator that enables surgeons to train the surgical
operations under the vision and sense of touch as if the
computer generated virtual patient is real.
❸
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4) Knowledge Extraction from Practical Data in Medicine
(fig.4)
We think that the widespread use of Electronic Medical
Records (EMRs) gives vast reusable knowledge. However,
the study of knowledge extraction from EMR data is on a
learning curve to use it as evidence. If we extract reusable
knowledge of medicine, it is necessary to benefit from
knowledge processing, cognitive science and natural
language processing, in addition to medical knowledge. We
study medical extraction knowledge from various practical
data of hospitals, World Wide Web, medical text and so on.
Recent Publications
Medical Informatics
Professor : Hiroyuki Yoshihara
Associate
Professor : Tomohiro Kuroda
Senior
Lecturer : Tadamasa Takemura
Assistant
Professor : Naoto Kume
Program-Specific Assistant Professor
: Kazuya Okamoto
TEL
: +81-75-751-3646
FAX
: +81-75-751-3076
e-mail
: [email protected]
URL
: http://www.kuhp.kyoto-u.ac.jp/~mi/
1. Yoshiaki Nakagawa, Tadamasa Takemura, Hiroyuki Yoshihara and Yoshinobu Nakagawa: A New
Accounting System for Financial Balance Based on Personnel Cost after the Introduction of a DPC/
DRG System,Journal of Medical Systems; (Online): ,2009
2. Kuroda Y, Takemura T, Kume N, Okamoto K, Hori K, Nakao M, Kuroda T, Yoshihara H: Semiautomatic development of optimized surgical simulator with surgical manuals., Stud Health
Technol Inform.; 125: 250-255, 2007
3. Naoto Kume, Kazuya Okamoto, Takashi Tsukasa, and Hiroyuki Yoshihara: VR-Based Self Brain
Surgery Game System by Deformable Volumetric Image Visualization, Virtual Reality, HCII 2007,
LNCS 4563; : 670 672, 2007
4. Tadamasa Takemura1, Kazuya Okamoto, Hyogyong Kim, Masahiro Hirose, Tomohiro Kuroda,
and Hiroyuki Yoshihara: Context-Based Loose Information Structure for Medical Free Text
Document, Human Interface,Part I, HCII 2007, LNCS 4557; : 544 548, 2007
5. Tomohiro Kuroda, Kazuya Okamoto, Ryo Kitauchi, Tadamasa Takemura, Naoki Ohboshi,
and Hiroyuki Yoshihara: Finding Origin Points for New Coordinate System Suitable for Sign
Animation, Digital Human Modeling, HCII 2007; : 415 422, 2007
Pharmacy
The aim of our laboratory is to establish the scientific bases of appropriate drug usage and pharmaceutical practice for
efficient and reliable pharmacotherapy. The efficacy and safety of drugs are closely related to their pharmacokinetics and
pharmacodynamics. Therefore, to clarify the pharmacokinetics in human, we have systematically developed the research from
drug transport analyses based on the molecular levels to the clinical pharmacokinetics. To settle the problem found in the
pharmacotherapy, we attempt to feedback the achievements of basic research (Bench) to clinical practice (Bedside) (Figure 1).
The pharmacokinetics for various drugs consist of four kinds
of processes such as absorption, distribution, metabolism
and excretion, and are regulated by various factors including
drug transporters. In our laboratory, research projects
have been carried out to determine optimal drug therapies
in view of pharmacokinetics, having with the theme
“laboratory and clinical studies of the pharmacokinetics,
effectiveness and toxicity of drugs”. For examples, we have
performed functional and molecular characterization of drug
transporters expressed in the intestine, kidney and liver,
and the establishment of personalized medicine based on
the molecular information of drug transporters. Especially,
the research on the renal drug excretion has been carried
out over 25 years with leading outcomes in this field: i.e.,
clarification of the transport mechanisms, cDNA cloning
of drug transporters, and elucidation of gene regulatory
mechanisms for drug transporters and so on. Furthermore,
we have expanded research projects to analyze genetic
polymorphisms for clinical practice or transcriptional
regulatory mechanism of drug transporters, and to identify
and analyze H+/organic antiporter in renal proximal tubules
and riboflavin transporter.
We contribute to personalized medicine of immunosuppressant
tacrolimus in the living donor liver transplantation (LDLT).
It was demonstrated that the intra- and interindividual
variability of tacrolimus pharmacokinetics in allograft
recipients is related to the intestinal expression level of
MDR1 (ABCB1), an active efflux pump located on the
intestinal brush-border membranes, and that the intestinal
expression level of MDR1 is a part of prognostic factor
for acute cellular rejection and mortality as well as a
pharmacokinetic factor in recipients of LDLT (Figure
2). In addition, we establish genome-based population
pharmacokinetic model requiring additional CYP3A5
polymorphism and MDR1 mRNA level for individualizing
the dosage regimen of tacrolimus in de novo pediatric LDLT
recipients. The information is utilized for the determination
of the initial dosage regimen for LDLT recipients.
Recently, we investigate the personalized medicine of
anticancer drugs. To improve safety and efficiency of
chemotherapy, we attempt to identify the factors affecting
inter-individual variations of pharmacokinetics or adverse
effects of anticancer drugs. The graduate students of
Medicine and Pharmaceutical Sciences play pivotal roles
for laboratory research, and all members have been tackling
with difficult scientific problems from various angles,
collaborating with pharmacists in Kyoto University Hospital.
Recent Publications
Pharmacy
Associate
Professor : Toshiya Katsura, Ph.D.
Senior
Lecturer : Satohiro Masuda, Ph.D.
Assistant
Professor : Hideyuki Motohashi, Ph.D.,
Masahide Fukudo, Ph.D.,
Atsushi Yonezawa, Ph.D.
TEL
: +81-75-751-3577
FAX
: +81-75-751-4207
e-mail
: [email protected]
URL
~yakuzai/main.htm
Kyoto University
1. Yonezawa, A., Inui, K.: Organic cation transporter OCT/SLC22A and H+/organic cation antiporter
MATE/SLC47A are key molecules for nephrotoxicity of platinum agents. Biochem Pharmacol.,
81(5):563-8. (2011)
2. Toyama, K., Yonezawa, A., Tsuda, M., Masuda, S., Yano, I., Terada, T., Osawa R, Katsura T,
Hosokawa M, Fujimoto S, Inagaki N, Inui K.: Heterozygous variants of multidrug and toxin
extrusions (MATE1 and MATE2-K) have little influence on the disposition of metformin in diabetic
patients., Pharmacogenet Genomics., 20(2):135-8. (2010)
3. Terada, T., and Inui, K.: Physiological and pharmacokinetic roles of H+/organic cation antiporters
(MATE/SLC47A). Biochem. Pharmacol., 75(9):1689-1696. (2008)
4. Masuda, S., and Inui, K.: An up-date review on individualized dosage adjustment of calcineurin
inhibitors in organ transplant patients. Pharmacol. Ther., 112(1):184-198. (2006) [review]
5. Fukudo, M., Yano, I., Masuda, S., Goto, M., Uesugi, M., Katsura, T., Ogura, Y., Oike, F., Takada,
Y., Egawa, H., Uemoto, S., Inui, K.: Population pharmacokinetic and pharmacogenomic analysis of
tacrolimus in pediatric living-donor liver transplant recipients. Clin. Pharmacol. Ther., 80(4):331345. (2006)
Experimental Therapeutics
To improve outcome of treatment or prevention from incurable diseases by creation and development of novel medical
treatments and diagnoses is one of the big missions given to the Kyoto University Graduate School of Medicine and to Kyoto
University Hospital. For this purpose, Kyoto University Hospital took a new strategy to convert the findings of basic medicine
and biology efficiently into novel clinical diagnosis and treatment by establishing a center, named Translational Research Center,
to promote such translational and synthetic research. Department of Experimental Therapeutics is for research to discover new
drugs and to develop novel methods for diagnosis and treatment. This department has two units, Fixed and Invited Research
Project Units. Fixed Research Project Unit, post-genome project, is to develop novel drugs and methods for clinical diagnosis by
analyzing human genome information, gene structure and expression.
Akira Shimizu, M.D., Ph.D.
Professor
On order to collect research seeds in nation-wide scale,
research proposals suitable for translation termed 3-5
years were invited and selected.
Collaborating with other Centers and Institutes of
Graduate School of Medicine, Fixed Project unit hosts
and supports the research by the Invited Research
Project Unit.
Our major subject of basic research is to analyze
molecular mechanisms underlying higher order
functions such as immunity. Active molecular
mechanisms appear to suppress IgE class switch
recombination (CSR), thereby preventing serious
complications during the normal course of the immune
response. Analyzing Id2-deficient mice, we found that
the switching efficiency of IgE is enhanced in Id2deficient B cells. Because of the lack of the Id2 gene,
increased active E2A and Pax5 proteins bind to the
epsilon germline promoter and augment the expression
of epsilon germline transcript (GLT). As a consequence,
Id2-deficient B cells undergo CSR to IgE at a much
higher frequency than wild-type B cells. On the other
hand, TGF-Beta1 is known to inhibit CSR to IgE.
We also found that Id2 acts as an effector molecule
involved in TGF- Beta1 signaling in activated B cells.
TGF- Beta1 induces Id2 expression and inhibits IgE
CSR. In summary, the TGF- Beta1-Id2 pathway is
required to keep the IgE concentration low in the serum.
Thus, Id2 might act as a afeguard molecule to prevent
harmful effects during the Th2-type immune reaction.
Furthermore, it found out that balance of transcription
factors including activators such as E2A and Pax5, and
inhibitors like Id2 is crucial for activation process and
function of lymphocyte. These knowledge are important
to understand control mechanisms of lymphocyte
activation, and application of these results to the
development of a novel treatment of allergy and of a
novel method to regulate immune reaction seems to be
promising. In addition to these, research on the molecule
mechanism for the polarity formation of lymphocytes
and the micro-environment formation at the place of
immunoreaction is also ongoing.
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❶ Id2 deficient mouse
shows hyper-IgE
phenotype.
Fr o ze n s e c t i o n s o f
mice immunized
by sheep red blood
c e l l s a r e o b s e r ve d
under fluorescence
microscope. B
lymphocytes, IgEs,
and germinal center
cells are stained
blue, red and green
respectively. Most of
B lymphocytes of Id2
deficient mouse (right
side) passively attach
IgE via low affinity
receptors reflecting a
high IgE concentration
in the serum, and cells
after IgE CSR (atrined
by all the three clolrs)
are seen in some of
the germinal centers of
Id2 deficient mouse.
❷ Model for the egulation
of IgE germline
transcription and AID
gene expression by
E2A, Pax5 and Id2.
Recent Publications
Experimental Therapeutics (Fixed Project)
Professor : Akira Shimizu
Senior
Lecturer : Manabu Sugai
Assistant
Professor : Tatsuya Ito
Lecturer (Special Appointment)
: Takafumi Ikeda
: Kayoko Endo
TEL
: +81-75-751-4749
FAX
: +81-75-751-4905
e-mail
: [email protected]
1. Essential role of Id2 in negative regulation of IgE class switching. Sugai, M., Gonda, H., Kusunoki,
T., Katakai, T., Yokota, Y. and Shimizu, A. Nature Immunol. 4, 25-30 (2003).
2. The balance between Pax5 and Id2 activities is the key to AID gene expression. Gonda, H., Sugai,
M., Nambu, Y., Katakai, T., Agata, Y., Mori, K. J., Yokota Y. and Shimizu, A. J. Exp. Med. 198,
1427-1437 (2003).
3. Tanscription-coupled events associating with immunoglobulin switch region chromatin. Nambu,
Y., Sugai, M., Gonda, H., Lee, C.-G., Katakai, T., Agata, Y., Yokota, Y. and Shimizu, A. Science
302, 2137-2140 (2003).
4. Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with
lymphocytes. Katakai, T., Hara, T., Sugai, M., Gonda, H. and Shimizu, A. J. Exp. Med. 200, 783795 (2004).
5. Spontaneous large-scale lymphoid neogenesis and balanced autoimmunity versus tolerance in the
stomach of H+/K+-ATPase-reactive TCR transgenic mouse. Katakai, T., Nomura, T., Gonda, H.,
Sugai, M., Agata, Y., Nishio, A., Masuda, T., Sakaguchi, S. and Shimizu, A. J. Immunol. 177, 78587867 (2006).
Clinical Trial Design and Management
Clinical trials are defined as intervention studies on human beings that designed to test the hypothesis for diagnostic techniques,
treatments, and disease preventions. Any novel medical technologies should be evaluated the efficacy and safety by clinical
trials. Our department is the first research branch in Japan to study and educate on clinical trial design, management, statistical
analysis, and assessment, which covers from the development of new treatments to establishing of standard therapy.
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Our department aims at “to improve treatment
outcomes for intractable diseases” and assists in
running investigator-sponsored clinical studies
(http://www.kutrc.org). At the study planning and
protocol development phase, we objectively assess
ethical and scientific appropriateness, and feasibility
of study. At the implementation phase, we carry out
the data management, monitoring, and statistical
analysis that is fundamental to the quality control
of study, independently with the sponsor and the
investigators. The staff members consist of medical
doctors, biostatisticians, data managers, monitors,
IT specialists, data analysts. For the projects in
Translational Research Center of Kyoto University
Hospital, we support protocol developments as
members of protocol committee, and conduct the
data management including CRF (case report forms)
designing, database designing, patient enrollment
and allocation, data entry and data review. We also
perform the monitoring including SDV (source data ❶ Software for Protocol Development (Study Designer)
verification) and safety monitoring, and the statistical
analysis including study designing, randomization
and data analysis. Since to know state-of-the-art for
treatment outcomes is most important for designing
clinical trials, we carry out lots of outcomes research
in collaboration with medical departments.
Recent Publications
Clinical Trial Design and Management
Associate
Professor : Satoshi Teramukai
Assistant
Professor : Harue Tada, Miyuki Niimi,
Shiro Tanaka, Kenichi Yoshimura
TEL
: +81-75-751-3858
FAX
: +81-75-751-4732
e-mail
: [email protected]
URL
: http://www.kutrc.org
Kyoto University
1. Teramukai S, Kitano T, Kishida Y, et al. Pretreatment neutrophil count as an independent
prognostic factor in advanced non-small-cell lung cancer: An analysis of Japan Multinational Trial
Organisation LC00-03. Eur J Cancer 2009;45: 1950-1958.
2. Kishida Y, Kawahara M, Teramukai S, et al. Chemotherapy-induced neutropenia as a prognostic
factor in advanced non-small-cell lung cancer: Results from Japan Multinational Trial Organization
LC00-03. Br J Cancer 2009;101: 1537-1542.
3. Tada H, Teramukai S, Fukushima M, et al. Risk factors for lower limb lymphedema after lymph
node dissection in patients with ovarian and uterine carcinoma. BMC Cancer 2009;9: 47.
4. Zhou B, Teramukai S, Yoshimura K, et al. Validity of cerebrospinal fluid biomarkers as endpoints
in early-phase clinical trials for Alzheimer’s disease. J Alzheimers Dis 2009;18: 89-102.
5. Nishizawa S, Kojima S, Teramukai S, et al. Prospective evaluation of whole-body cancer screening
with multiple modalities including [18F]fluorodeoxyglucose positron emission tomography in a
healthy population: A preliminary report. J Clin Oncol 2009;27: 1767-1773.
6. Zohar S, Teramukai S, Zhou Y. Bayesian design and conduct of phase II single-arm clinical trials
with binary outcomes: A tutorial. Contemp Clin Trials 2008;29: 608-616.
7. Egawa H, Teramukai S, Haga H, et al. Present status of ABO-incompatible living donor liver
transplantation in Japan. Hepatology 2008;47: 143-152.
8. Teramukai S, Ochiai K, Tada H, Fukushima M. PIEPOC: A new prognostic index for advanced
epithelial ovarian cancer – Japan Multinational Trial Organization OC01-01. J Clin Oncol 2007;25:
3302-3306.
9. Teramukai S, Nishiyama H, Matsui Y, Ogawa O, Fukushima M. Evaluation for surrogacy of end
points by using data from observational studies: Tumor downstaging for evaluating neoadjuvant
chemotherapy in invasive bladder cancer. Clin Cancer Res 2006;12: 139-143.
Clinical Innovative Medicine
Translational research center was established to translate potential therapies into clinical outcomes. A new paradigm is sought
to obviate many of the problems associated with translation of basic science findings. The Department of Clinical Innovative
Medicine was founded in 2002 for this purpose to organize and head a medical team that could pursue highly advanced therapies
safely and relevantly. We have collaborated with Department of Experimental Therapeutics in order particularly to promote the
preclinical studies for clinical application. We are also eager to guarantee scientific and ethical relevance of the clinical trials
and have co-operated with the Department of Clinical Design and Management. Our physicians, research nurses, and research
pharmacists are not only leading multidisciplinary team but also are expert at OPC and wards, getting informed consent from
the patients, and caring after the patients who have left the hospital. Based on these achievements, we wish to propose the new
paradigm to enable rational translation of important basic science findings into clinical use.
We focus our research target on creation of a
new clinical paradigm of translational research
that emphasizes efficacy and clinically relevant
outcomes. We furthermore wish to create a system
for rigorous preclinical testing of promising
potential therapies with clinical trial approaches so
that preclinical research would be assessed under
standardized criteria. We are eager to educate
graduate students interested in clinical studies who
wish to learn while they are working for the patients.
Also, scientific basis of the trials, i.e., blinded,
randomized, multicentered, and adequately powered
studies using standardized methods will be taught.
We do call for the young promising students who
wish to study with us to lead the clinical studies of the
nation.
Masayuki Yokode, M.D., Ph.D.
Professor
❶
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❸
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❹
●
❺
●
❶ Paradigm of Translational Research
❷ informed consent
❸ members
Recent Publications
Clinical Innovative Medicine Translational
Research Center
Professor : Masayuki Yokode
Senior
Lecturer : Toshinori Murayama
Assistant
Professor : Eriko Sumi, Manabu Minami,
Toshiko Ihara, Noboru Ashida,
Takahiro Horie
TEL
: +81-75-751-4743
FAX
: +81-75-761-6816
e-mail
: [email protected]
1. Hatta T, Murayama T, Narita K, Sumi E, Yokode M Trend Analysis of Informed Consent Research
in Clinical Trials: Comprehensive Retrieval via Electronic Databases. Jpn J ClinPharmacol
Therapeutics 2011; 42: 21-25.
2. Minami M, Matsumoto S, Horiuchi H. Cardiovascular side-effects of modern cancer therapy. Circ
J 2010; 74:1779-1786.
3. Nakase H, Fujiyama Y, Oshitani N, Oga T, Nonomura K, Matsuoka T, Esaki Y, Murayama T,
Teramukai S, Chiba T, Narumiya S. Effect of EP4 agonist (ONO-4819CD) for patients with mild
to moderate ulcerative colitis refractory to 5-aminosalicylates: A randomized phase II, placebocontrolled trial. Inflamm Bowel Dis 2010; 16: 731-733.
4. Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, Kinoshita M, Kuwabara Y,
Marusawa H, Iwanaga Y, Hasegawa K, Yokode M, Kimura T, Kita T. MicroRNA-33 encoded
by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo.
ProcNatlAcadSci U S A. 2010; 107:17321-17326.
5. Tamura Y, Sugimoto M, Murayama T, Minami M, Nishikaze Y, Ariyasu H, Akamizu T, Kita T,
Yokode M, Arai H. C-C Chemokine receptor 2 inhibitor improves diet-induced development of
insulin resistance and hepatic steatosis in mice. J ArteriosclerThromb 2010; 17: 219-228.
6. Sumi E, Murayama T, Yokode M. A survey of attitudes toward clinical research among physicians
at Kyoto University Hospital. BMC Med Edu 2009; 9: 75.
- Clinical Medicine (Core Departments) - Human Brain Research Center
Brain Pathophysiology / Functional Brain Imaging
Human Brain Research Center
We are engaged in the research works on the human brain function using non-invasive technique, such as MRI, PET, MEG,
TMS and so on. Our main purpose is directed to disclose the functional localization and connectivity of the human brain, and
research the physiological mechanisms of the disorders in the CNS. We think that it is the most important thing to explore the
brain function from the various aspects using available imaging or physiological apparatus.
Hidenao Fukuyama, M.D., Ph.D.
Professor
Recent advances on the molecular imaging stimulate
us to do the work related this field. The basic
concept is to expand the functional significance of
the gene or subsequent protein products in vivo.
The neuroscience itself is dedicated to find out
the functions of the human brain, but we have to
explore the animal brain for its final goal, because
human brain is specific to human being and also we
cannot do any invasive technique to the human brain
except for the special occasions. It was reported that
beta-amyloid is visualized using PET. In the near
future, we can image the various kinds of proteins
or other substances without invasive exploratory
procedures. This is the dream and final direction of
the neuroscience in one aspect.
Another is the research to help the disadvantaged
brain with the knowledge of the normal brain
functions. Rehabilitation is regarded as one of
the regeneration medicine. HBRC is one of the
departments that concern with the neuroscience and
clinical neurology. Therefore, we have also keen
interest in this aspect, and devote the efforts to make
help for disadvantaged people.
We will welcome every person to join us and do the
research activities, who have the similar interests.
❶
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❷
●
❸
●
❹
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❶ 306 channel whole-head MEG
measures neuronal electrical
activity at high temporal
resolution.
❷ 3 tesla MRI scanner visualizes
brain structure and function at
high spatial resolution.
❸ Tr a c t o g r a p h y a n a l y s i s o f
diffusion MRI data identifies
connectivity among brain areas.
❹ Member of the laboratory.
Recent Publications
Brain Pathophysiology / Functional Brain
Imaging
Human Brain Research Center
Professor : Hidenao Fukuyama, Denis Le Bihan
Associate
Professor : Hiroshi Yamauchi, Tatsuya Mima
Assistant
Professor : Nobukatsu Sawamoto,
Shinichi Urayama
TEL
: +81-75-751-3695
FAX
: +81-75-751-3202
e-mail
: [email protected]
URL
: http://hbrc.kuhp.kyoto-u.ac.jp/
Kyoto University
1. Badry, R., Mima, T., Aso, T., Nakatsuka, M., Abe, M., Fathi, D., Foly, N., Nagiub, H., Nagamine,
T. and Fukuyama, H. (2009). "Suppression of human cortico-motoneuronal excitability during the
Stop-signal task." Clin Neurophysiol 120(9): 1717-23.
2. Aso, T., Urayama, S., Poupon, C., Sawamoto, N., Fukuyama, H. and Le Bihan, D. (2009).
"An intrinsic diffusion response function for analyzing diffusion functional MRI time series."
Neuroimage 47(4): 1487-95.
3. Kohno, S., Sawamoto, N., Urayama, S., Aso, T., Aso, K., Seiyama, A., Fukuyama, H. and Le
Bihan, D. (2009). "Water-diffusion slowdown in the human visual cortex on visual stimulation
precedes vascular responses." J Cereb Blood Flow Metab 29(6): 1197-207.
4. Takaya, S., Mikuni, N., Mitsueda, T., Satow, T., Taki, J., Kinoshita, M., Miyamoto, S., Hashimoto,
N., Ikeda, A. and Fukuyama, H. (2009). "Improved cerebral function in mesial temporal lobe
epilepsy after subtemporal amygdalohippocampectomy." Brain 132(Pt 1): 185-94.
5. Aso, K., Hanakawa, T., Aso, T. and Fukuyama, H. "Cerebro-cerebellar Interactions Underlying
Temporal Information Processing." J Cogn Neurosci.
- Clinical Medicine (Core Departments) - Department of Organ Preservation Technology
Contributed Chairs
We research the mechanisms of functional deterioration of organs, tissues, and cells during preservation. Further, we develop
novel methods and techniques to effectively preserve organs, tissues, and cells.
Kyoto University has developed the original organ preservation solution named ET-Kyoto solution, and proven its protective
effect in various organ preservation. Based on the knowledge, our department was established in August 2006 to investigate wide
range of clinics-oriented themes.
Transplantation of various organs including the
lung, heart, liver, kidney, islets, and small intestine
has been established as the solo therapeutic option
for end-stage organ dysfunction. Additionally,
various relating therapies including bone marrow
transplantation for leukemia, immuno-cell therapies
for cancer, and replantation of amputated digits are
emerging.
However, the quality and quantity of organs, tissues
and cells transplanted after preservation is not yet
satisfactory. Therefore, elucidating the mechanisms
of functional deterioration after preservation and
improving the quality of organs, tissues, and cells
would directly benefit patients for those advanced
therapies. Reliable methods of preservation would
enable the use of marginal donors and alleviate the
shortage of donor organs. Good function of preserved
organs, tissues, and cells would lessen complications
after therapies and contribute to the medical
economics. Further, knowledge on organ, tissue and
cell preservation would also provide better results in
regenerative medicine.
Our department would like to collaborate many
researches, and perform basic as well as pre-clinical
studies.
❶
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❸
●
❹
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❶ Rat lung ex vivo perfusion
model newly developed by our
department (Figure 1).
❷ The device enabled us to measure
the physiological data on time in
various conditions Harvested rat
heart-lung block (Figure 2, Ref. 4
and 5)
❸ Clinical application of our organ
preservation solution, ET-Kyoto
solution (Figure 3). ET-Kyoto
solution showed both a splendid
lung function and histologic
findings even in the setting of more
than 10 hours of ischemia in a
clinical lung transplantation. This
solution has been used not only
lung transplantation but also many
other transplantations, such as
kidney, liver, and islet cell.
❹ Large animal ex vivo perfusion
model, currently being developed
by our department (Figure 4). To
investigate organ function in a
setting closer to clinical situation,
we are currently preparing and
developing a large animal ex vivo
perfusion model.
Recent Publications
Associate
Professor : Toru Bando, MD, PhD
Assistant
Professor : Takuji Fujinaga, MD, PhD,
Fengshi Chen, MD, PhD,
Xiangdong Zhao, MD, PhD
TEL
: +81-75-751-3837
FAX
: +81-75-751-4647
e-mail
: [email protected]
1. Zhao X, Koshiba T, Nakamura T, Tsuruyama T, Li Y, Bando T, Wada H, Tanaka K. ET-Kyoto
Solution plus Dibutyryl Cyclic Adenosine Monophosphate is Superior to University of Wisconsin
Solution in Rat Liver Preservation. Cell Transplantation, in press.
2. Chen F, Kondo N, Sonobe M, Fujinaga T, Wada H, Bando T. Expression of endothelial specific
adhesion molecules after cardiac arrest. Int Cardiovasc Thorac Surg 2008 Feb 15; [Epub ahead of
print].
3. Fujinaga T, Nakamura T, Fukuse T, Chen F, Zhang J, Ueda S, Hamakawa H, Omasa M, Sakai H,
Hanaoka N, Wada H, Bando T. Isoflurane inhalation after circulatory arrest protects against warm
ischemia reperfusion injury of the lungs. Transplantation 2006; 82: 1168-72.
4. Chen F, Nakamura T, Fujinaga T, Zhang J, Hamakawa H, Omasa M, Sakai H, Hanaoka N, Bando
T, Wada H, Fukuse T. Protective effect of a nebulized Beta2-adrenoreceptor agonist in warm
ischemic–reperfused rat lungs. Ann Thorac Surg 2006; 82: 465-71.
5. Noguchi H, Ueda M, Nakai Y, Iwanaga Y, Okitsu T, Nagata H, Yonekawa Y, Kobaya N, Nakamura
T, Wada H, Matsumoto S. Modified two-layer preservation method (M-Kyoto/PFC) improves islet
yields in islet isolation. Am J Transplant 2006; 6:496-504.
- Clinical Medicine (Core Departments) - Department of Respiratory Care and Sleep Control Medicine
Contributed Chairs
The Department of Respiratory Care and Sleep Control Medicine is a new department which was started on April 1, 2008.
The purpose of the department is to investigate the blood gas levels which are essential to life. One of our key research areas
is hypoxemia with or without hypercapnia, and research in this department includes 1) refractory acute respiratory failure,
including acute respiratory distress syndrome, 2) sleep disordered breathing such as sleep apnea, which has a significant effect
on life-style related diseases such as cardiovascular diseases, and 3) sleep associated symptoms such as excessive daytime
sleepiness. From translational research, we hope to develop a new therapy for respiratory failure and sleep disordered breathing.
Kazuo Chin (Hwa Boo Jin) M.D., Ph.D.
Professor
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Based on pulmonary physiology such as the
regulation of breathing while awake and asleep,
gas exchange, and lung mechanics, the purpose
of the Department of Respiratory Care and Sleep
Control Medicine is to investigate blood gas
levels which are essential life. From translational
research, we hope to develop new therapies for
respiratory failure and sleep disordered breathing.
In addition, this department teaches how to manage
respiratory failure, sleep disordered breathing and
excessive daytime sleepiness. For example, we
teach how to manage acute or chronic respiratory
failure by using oxygen, noninvasive ventilation
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(NIV) such as continuous positive airway pressure
(CPAP), noninvasive positive pressure ventilation
(NPPV) and adapted servo ventilation (ASV), and
intermittent positive pressure ventilation (IPPV) via
tracheostomy or intubation (Figure 1). Recently, it
has been shown that intermittent and/or sustained
hypoxia (IH and/or SH), which are induced by
sleep disordered breathing such as sleep apnea,
have significant effects on morbidity and mortality
through transcriptional factors such as NFkappaB
❸
and hypoxia inducible factor-1 (HIF-1). We will ●
❶ Respiratory complications in children
research the effects of IH and SH using molecular
following living donor liver transplantation
biology and new techniques (Figure 2). We’ll also
improved by using noninvasive positive
investigate the pathophysiological effects of IH and
pressure ventilation.
SH on humans and animals by using noninvasive
❷ A machine which can produce intermittent
and sustained hypoxia in several cells.
methods such as polysomnography. Through such
❸ Abdominal adipose tissue accumulation
research we will determine the effects of IH and SH
and serum leptin levels decrease after
on refractory respiratory failure, metabolic syndrome
CPAP treatment
(Figure 3), and life-style related diseases such as
❹ Effects of PGF2alpha on proliferation and
cardiovascular diseases and diabetes mellitus. In
collagen production of lung fibroblasts.
the near future, we will want to make personalized
medicine for sleep disturbance including sleep
disordered breathing. We also hope to develop new Recent Publications
machines and drugs which manage several refractory 1. Chin K, Oga T, Takahashi K, Takegami M, Nakayama-Ashida Y, Wakamura T, Sumi K, Nakamura
respiratory failures, including acute respiratory
T, Horita S, Oka Y, Minami I, Fukuhara S, Kadotani H. Associations between obstructive sleep
apnea, metabolic syndrome and sleep duration, as measured with an actigraph, in an urban male
distress syndrome and pulmonary fibrosis (Figure 4).
Professor : Kazuo Chin (Hwa Boo Jin)
Associate
Professor : Tomomasa Tsuboi
Senior
Lecturer : Toru Oga
Assistant
Professor : Takefumi Hitomi
TEL
: +81-75-751-3852
FAX
: +81-75-751-3854
e-mail
: [email protected]
Kyoto University
working population in Japan. Sleep 2010; 33:89-95.
2. Oga T, Matsuoka T, Yao C, Nonomura K, Kitaoka S, Sakata D, Kita Y, Tanizawa K, Taguchi Y,
Chin K, Mishima M, Shimizu T, Narumiya S. Prostaglandin F2alpha receptor signaling facilitates
bleomycin-induced pulmonary fibrosis independently of transforming growth factor-beta. Nat Med
2009; 15: 1426- 30.
3. Takahashi K, Chin K, Nakamura H, Morita S, Sumi K, Oga T, Matsumoto H, Niimi A, Fukuhara
S, Yodoi J, Mishima M. Plasma thioredoxin, a novel oxidative stress marker, in patients with
obstructive sleep apnea before and after nasal continuous positive airway pressure. Antioxidants &
Redox Signaling 2008; 10:715-726.
4. Chin K, Nakamura T, Fukuhara S, Takahashi K, Sumi K, Matsumoto H, Niimi A, Mishima M,
Nakamura T. Falls in blood pressure in patients with obstructive sleep apnoea after long-term nasal
continuous positive airway pressure treatment. Journal of Hypertension 2006; 24;2091-2099
5. Chin K, Uemoto S, Takahashi K, Egawa H, Kasahara M, Fujimoto Y, Sumi K, Mishima M,
Sullivan CE, Tanaka K. Noninvasive ventilation for pediatric patients including those under a year
undergoing liver transplantation. Liver Transplantation 2005;11:188-195.
- Clinical Medicine (Core Departments) - Department of Translational Clinical Oncology
Research in the field of clinical oncology aims to advance the treatment of cancer, with a particular focus on chemotherapy,
but also supportive care. Translational clinical oncology is a field of study that aims to translate the findings arising from
basic research (e.g. in the fields of pharmacology, pharmacogenetics or tumor biology) into clinical oncology practice. The
Department of Translational Clinical Oncology was founded in October 2003 to facilitate such translational research. It
was also founded with the aim of developing an effective database system to support the implementation of clinical trials,
which are essential to providing patients with new drugs for cancer chemotherapy. Based at the Outpatient Oncology Unit
of Kyoto University Hospital, the department is also dedicated to developing a database system to support safe and effective
chemotherapy for cancer patients.
❶ Comparison of standard clinical
❶
●
database systems and our cancer
Research activities
clinical database system (Cyber
(1) Development of a database system to support
Oncology®). Generally, when an
attempt is made to use electronic
practical cancer chemotherapy: We have developed
health record (EHR) data for
a database system that allows doctors, nurses,
clinical studies, data are obtained
pharmacists, and other practitioners to share patient
directly from the medical records. In
information, and can help identify problems for
contrast, Cyber Oncology® acts as
discussion in clinical conferences.
a front-end component of the EHR
system.
(2) Development of a database system to support
❷ Architecture of the cancer clinical
clinical trials: We have developed a database system ●
❷
database system. The system
that outputs case report forms by using information
comprises four sub-systems: the
from patients’ electronic health records (e.g. adverse
Cyber Oncology® cancer clinical
events or laboratory data).
database system, the clinical
support system, the daily reports
(3) Clinical study of cancer chemotherapy: Using
system and the data analysis
the above-mentioned clinical trial database system,
system.
we have conducted a number of phase II clinical
❸ Phase II study of S-1 and docetaxel
trials such as TS-1 and docetaxel for the treatment
for previously treated patients with
of previously treated non-small cell lung cancer, and
locally advanced or metastatic
non-small cell lung cancer:
TS-1 and gemcitabine for the treatment of recurrent
Kaplan–Meier sur vival cur ves
or inoperable biliary tract cancers. We have also
demonstrating overall (solid line)
conducted some outcomes studies, for example of ●
❸
and progression-free (dashed line)
modified FOLFOX6 for the treatment of advanced or
survival. OS overall survival, PFS
recurrent colorectal cancer.
progression-free survival
(4) Clinical study of supportive care in cancer
chemotherapy: We are exploring measures to
alleviate the pain associated with gemcitabine
infusion, and investigating the risk factors for
chemotherapy-induced anemia and oxaliplatininduced allergic reactions.
(5) Pharmacogenetic study in cancer chemotherapy:
We are investigating the relationships between
genetic polymorphisms and the incidence of adverse
events and/or the effectiveness of a treatment. We are
currently studying pharmacogenetic factors in TS-1 Recent Publications
treatment for gastrointestinal cancer and oxaliplatin- 1. Yamamoto K, Matsumoto S, Tada H, Yanagihara K, Teramukai S, Takemura T, Fukushima
M. A data capture system for outcomes studies that integrates with electronic health records:
induced sensory neuropathy.
Program-Specific Associate Professor
: Kazuhiro Yanagihara
Program-Specific Senior Lecturer
: Takafumi Nishimura
: Shigemi Matsumoto, Toshiyuki Kitano
TEL
: +81-75-751-4770
FAX
: +81-75-751-4772
e-mail
: [email protected]
URL
~oncolctr/index.html
development and potential uses. J Med Syst. 2008;32:423-7.
2. Yanagihara K, Yoshimura K, Niimi M, Yasuda H, Sasaki T, Nishimura T, Ishiguro H, Matsumoto
S, Kitano T, Kanai M, Misawa A, Tada H, Teramukai S, Mio T, Fukushima M. Phase II study of
S-1 and docetaxel for previously treated patients with locally advanced or metastatic non-small cell
lung cancer. Cancer Chemother Pharmacol. 2010 ;66(5):913-8.
3. Kanai M, Yoshioka A, Tanaka S, Nagayama S, Matsumoto S, Nishimura T, Niimi M, Teramukai
S, Takahashi R, Mori Y, Kitano T, Ishiguro H, Yanagihara K, Chiba T, Fukushima M, Matsuda F.
Associations between glutathione S-transferase pi Ile(105)Val and glyoxylate aminotransferase
Pro(11)Leu and Ile(340)Met polymorphisms and early-onset oxaliplatin-induced neuropathy.
Cancer Epidemiol. 2010 ;34(2):189-93.
4. Mori Y, Nishimura T, Kitano T, Yoshimura K, Matsumoto S, Kanai M, Hazama M, Ishiguro
H, Nagayama S, Yanagihara K, Teramukai S, Chiba T, Sakai Y, Fukushima M. Oxaliplatin-free
interval as a risk factor for hypersensitivity reaction among colorectal cancer patients treated with
FOLFOX. Oncology. 2010;79:136-43.
5. Kitano T, Tada H, Nishimura T, Teramukai S, Kanai M, Nishimura T, Misawa A, Yoshikawa K,
Yasuda H, Ishiguro H, Matsumoto S, Yanagihara K, Fukushima M. Prevalence and incidence of
anemia in Japanese cancer patients receiving outpatient chemotherapy. Int J Hematol. 2007;86:3741.
- Translational Research Center
Ghrelin is a novel acylated peptide discovered from the stomach in 1999 and exhibits a variety of biological activities including
the stimulation of growth hormone release and food intake. We are attempting to apply ghrelin to the treatment of disorders
related to appetite and growth hormone secretion.
Takashi Akamizu M.D., Ph.D.
Special Appointment Professor
1.Basic Research
· Pathophysiological role of ghrelin
· New physiological function of ghrelin
· Regulation of ghrelin secretion/production
❶
●
2.Clinical Trials
· Phase I: finished
· Phase II: Two trials finished, One ongoing
3.Education
Drug discovery using peptides
Methodology and systems of translational research
❷
●
❶ Structure of Ghrelin
❷ Function and Clinical applications
of Ghrelin
❸ Lab Personnel
❸
●
Recent Publications
Special Appointment Professor
: Takashi Akamizu
Assistant Professor
: Hiroshi Iwakura, Hiroyuki Ariyasu
TEL
: +81-75-751-4720
FAX
: +81-75-751-4731
e-mail
: [email protected]
URL
~ghrelin/
Kyoto University
1. Iwakura H, Li Y, Ariyasu H, Hosoda H, Kanamoto N, Bando M, Yamada Go, Hosoda K, Nakao
K, Kangawa K, Akamizu T. Establishment of a novel ghrelin-producing cell line. Endocrinology.
151(6):2940-5, 2010
2. Ariyasu H, Iwakura H, Yamada G, Kanamoto N, Bando M, Kohno K, Sato T, Kojima M, Nakao
K, Kangawa K, Akamizu T. A post-weaning reduction in circulating ghrelin temporarily alters
GH responsiveness to GHRH in male mice, but does not affect somatic growth. Endocrinology.
151(4):1743-50, 2010
3. Yamada G, Ariyasu H, Iwakura H, Hosoda H, Akamizu T, Nakao K, Kangawa K. Generation of
transgenic mice overexpressing a ghrelin analog. Endocrinology. 151(12):5935-40, 2010
4. Iwakura H, Ariyasu H, Li Y, Kanamoto N, Bando M, Yamada Go, Hosoda H, Hosoda K, Shimatsu
A, Nakao K, Kangawa K, Akamizu T: A mouse model of ghrelinoma exhibited activated growth
hormone-insulin-like growth factor I axis and glucose intolerance. Am J Physiol Endocrinol Metab.
297(3):E802-11, 2009.
5. Ariyasu H, Iwakura H, Yamada G, Nakao K, Kangawa K, Akamizu T: Efficacy of Ghrelin as a
therapeutic approach for age-related physiologic changes. Endocrinology. 149:3722-8, 2008.
- Translational Research Center
Lactosome Project
On the basis of molecular imaging technique, which is promising for early detection of solid tumors, we aim at development of
a new imaging probe for novel clinical diagnosis. Our strategy is to utilize a novel nanocarrier, molecular assembly of poly(Llactide)-co-polypeptide and named “lactosome”, to be equipped with a signal unit and a targeting unit. Lactosome accumulates
passively in tumors. With labeling and entrapment of anti-cancer drugs, “lactosome” is going to be an excellent imaging/delivery
system.
Shunsaku Kimura, Ph.D.
Professor
❶
●
i) Cooperation of medicine, engineering, and
pharmacology: Cutting-edge medical technology
will be achieved by collaborative researches between
medicine, engineering, and pharmacology. Clinical
application of the technology is prime for our
collaboration to develop a novel diagnosis method
here for early detection of solid tumors by molecular
imaging.
ii) Imaging/targeting: Combination of a signal unit,
targeting unit, and anti-cancer drugs is realized in
the present project by using lactosome, molecular
assembly of poly(L-lactide)-co-polypeptide, as
nanocarrier. With this conjugation, simultaneous
imaging and targeting will be possibly attained.
iii) Lactosome: Lactosome has an advantage as
nanocarrier because of its high stealth effect. We
have succeeded thus in imaging of tiny liver cancer
grafted in liver. For further high functionalization
of lactosome, we are optimizing the molecular ❶ Imaging of liver cancer (HepG2) grafted in liver by using lactosome labeled with NIR
fluorescence probe of ICG.
assembly.
iv) Clinical application: Medicinal and
pharmacological test, pharmacokinetics studies,
safety pharmacologic test, and toxicity test are
scheduled in the project period of five years. Further,
we will prepare the protocol for clinical trial under
cooperation of Translational Research Center.
Lactosome Project
Professor : Shunsaku Kimura
Assistant
Professor : Kensuke Kurihara
TEL
: +81-75-383-2400
FAX
: +81-75-383-2401
e-mail
: [email protected]
URL
: http://pixy.polym.kyoto-u.ac.jp/
lactosome.html
Recent Publications
1. H. Tanisaka, S. K. Kondoh, A. Makino, S. Tanaka, M. Hiraoka, S. Kimura, Near-Infrared
Fluorescent Labeled Peptosome for Application to Cancer Imaging, Bioconjugate Chem., 19, 109117 (2008)
2. K. Kitagawa, T. Morita, S. Kimura, A Helical Molecule That Exhibits Two Length in Response an
Applied Potential, Angew. Chem., Int. Ed., 44, 6330-6333 (2005)
3. S. Yasutomi, T. Morita, Y. Imanishi, S. Kimura, A Molecular Photodiode System That Can Switch
Photocurrent Direction, Science, 304, 1944-1947 (2004)
4. S. Kimura, Y. Imanishi, Enkephalin-Cell Interactions, Vitamins and Hormones, 59, 133-158 (2000)
5. K.-Y. Nam, M. Hiro, S. Kimura, H. Fujiki, Y. Imanishi, Permeability of a Non-TPA-Type Tumor
Promoter, Okadaic Acid, through Lipid Bilayer membrane, Carcinogenesis, 11, 1171-1174 (1990)
- Radiation Biology Center
Radiation System Biology
(Laboratory of Genome Maintenance)
Chromosomal DNA, a carrier of the blue print of life, must be faithfully duplicated and equally delivered to two daughter
cells. Cells with extra chromosomes or less chromosomes (aneuploids), which are generated through unequal segregation
of chromosomes, are a primary cause of genetic diseases such as Down syndrome. They have a great impact on tumor
development/progression as well. We study mechanisms required for equal segregation of chromosomes with yeast and cultured
human cells as major research materials.
Tomohiro Matsumoto, Ph.D.
Professor
A series of the biochemical reactions necessary for
self-duplication of life are orderly programmed
in the cell cycle. In particular, most of the
reactions, which are initiated once and only once
at a specific stage of the cell cycle (such as DNA
replication and segregation), are triggered by the
completion of the preceding reaction. It is generally
accepted that negative feedback loops (so called
checkpoints) are responsible for suppression of
the onset of a reaction until the completion of the
preceding reaction. That sister chromatid separation
must follow the completion of attachment of
the spindle to all kinetochores is an important
rule for equal segregation of chromosomes. The
spindle checkpoint, our major research subject,
is a surveillance mechanism to regulate cellular
apparatus for compliance with this rule. It is a
unique negative feedback that converts/amplifies a
physical signal sensed by kinetochores (attachment
of the spindle and/or tension) and regulates the
timing of the sister chromatid separation. Mad2, a
signal carrier of this feedback, plays a vital role in
the spindle checkpoint. It is specifically localized
at unattached kinetochores that are the origin of the
checkpoint signal. Mad2 targets CDC20 and inhibits
its activity to promote sister chromatid separation.
We study Mad2, a central player of the spindle
checkpoint, to reveal mechanisms, which regulate the
activity of Mad2.
❶ Sister chromatid separation at the
onset of anaphase. Chromosomes
(red) and the spindle (green) were
stained with fluorescence.
❷ Distribution of Mad2 at prophase.
Nuclear membrane (red), Mad2
(green) and chromosomal DNA (blue)
were stained with fluorescence.
❸ Staffs
❶
●
❷
●
❸
●
Recent Publications
Radiation System Biology
Professor : Tomohiro Matsumoto
Assistant
Professor : Toshiyuki Habu
TEL
: +81-75-753-7552
FAX
: +81-75-753-7564
e-mail
: [email protected]
URL
: http://www.rbc.kyoto-u.ac.jp/
Kyoto University
1. Guohong Xia, Xuelian Luo, Toshiyuki Habu, Josep Rizo, Tomohiro Matsumoto, and Hongtao Yu
(2004) Conformation-specific binding of p31comet to Mad2 antagonizes the function of Mad2 in
the spindle checkpoint. EMBO J. 23:3133-3143.
2. Luo X., Tang Z., Xia, G., Wassmann K., Matsumoto T., Rizo, J. and Yu H. (2004) The Mad2
spindle checkpoint protein has two distinct natuively folded states. Nat Struct Mol Biol. 11:338345.
3. Habu, T., Kim, S. H., Weinstein, J., and Matsumoto, T. (2002). Identification of a Mad2-binding
protein, Cmt2, and its role in mitosis. EMBO J. 21: 6419-6428.
4. Kim, S. H., Lin, D. P., Matsumoto, S., Kitazono, A. and Matsumoto, T. (1998). Fission yeast Slp1:
An effector of the Mad2-dependent spindle checkpoint. Science 279:1045-1047.
(Division of Chromatin Regulatory Network)
The purpose of our research is to clarify the role of chromatin remodeling, which is required for the DNA metabolisms such as
transcription, DNA replication, and DNA repair. In particular, we focus on the molecular mechanisms by which histone modifier
complexes regulate the histone eviction as chromatin remodeling machinery upon DNA damage induced by ionizing radiation.
We use the protein complex purification system in combination with genetic analysis to determine the relationship between
histone eviction and DNA damage signaling pathway. Our goal is to understand how histone eviction activates DNA damage
signaling pathways and functions as an anti-cancer signaling.
Eukaryotic genome is tightly packed into the
chromatin, a hierarchically organized complex of
DNA, histone and nonhistone proteins. This packing
represents a common obstacle for most of the
DNA functions. Concerning transcription, covalent
modifications of core histone N-termini and ATPdependent nucleosome remodeling plays a role
in regulation of gene expression in the chromatin
context. On the other hand, role of these chromatin
modifications in other aspects of DNA metabolism,
especially DNA repair, remains largely unexplored.
We have shown that TIP60 histone acetylase
complex involved in DNA repair and apoptosis.
However, it remains unknown how TIP60 complex
involve in DNA repair. To better understand the
mechanism of TIP60 complex in DNA repair, TIP60
complex purifies from chromatin soluble fraction
after exposure of ionizing radiation. As a result,
the TIP60 complex is associated with chromatin
including histone H2AX after DNA damage. Histone
H2AX, histone H2A variant, is phosphorylated
at the site of DNA double-strand breaks (DSBs).
We found that TIP60 acetylates histone H2AX.
By acetylating H2AX, TIP60 stimulates its
ubiquitination by the ubiquitin-conjugating
enzyme UBC13. Furthermore, we revealed that the
acetylation-dependent ubiquitination by the TIP60UBC13 complex leads to the eviction of H2AX
from damaged chromatin using live cell imaging and
UV laser micro-irradiation. Since ubiquitination of
H2AX is required for the recruitment of DNA repair
and checkpoint proteins at the damage site, TIP60/
UBC13-dependent eviction of H2AX may function
as a molecular link between DNA damage sensing
and chromatin remodeling. We are now investigating
the role of the eviction of H2AX upon DNA damage
in chromatin remodeling and checkpoint activation.
❶
●
❷
●
❸
●
❶ Model for the role of TIP60 and
UBC13 in DNA damage response.
The TIP60 complex is recruited
to the damaged chromatin
immediately after induction of
DSBs and acetylates H2AX.
UBC13 is recruited and/or the
activity of UBC13 is modulated
by TIP60, facilitates polyubiquitination of H2AX, resulting
in histone H2AX eviction for the
repair of DSBs.
❷ The strategy fro the TIP60 complex
purification Nuclear extracts were
prepared from HeLa cells stably
expressing Flag-HA tagged TP60.
Affinity purification by using antFlag and anti-HA antibody was
performed. Purified TIP60 complex
was analyzed by SDS-PAGE and
then the components of the TIP60
complex were determined by Mass
Spectrometry analysis.
❸ SDS-PAGE analysis of the TIP60
complex by silver staining.
Recent Publications
Laboratory of Chromatin Regulatory Network,
Department of Mutagenesis,
Associate
Professor : Tsuyoshi Ikura, D.D.S., Ph.D.
TEL
: +81-75-753-7556
FAX
: +81-75-753-7564
e-mail
: [email protected]
1. Ikura, T., Ogryzko, V V., Grigoriev, M., Groisman, R., Wang, J., Horikoshi, M., Scully, R., Qin, J.,
Nakatani, Y. Involvement of the TIP60 Histone Acetylase Complex in DNA repair and apoptosis
(2000). Cell. 102: 463-473.
2. Fuchs, M., Gerber, J., Drapkin, R., Sif, S., Ikura, T., Ogryzko, V., Lane, WS., Nakatani, Y.,
Livingston, DM. The p400 complex is an essential E1A transformation target (2001).Cell. 106:
297-307.
3. Ikura, T., Tashiro, S., Kakino, A., Shima, H., Jacob, N., Amunugama, R., Yoder, K., Izumi, S.,
Kuraoka, I., Tanaka, K., Kimura, H., Ikura, M., Nishikubo, S., Ito, T., Muto, A., Miyagawa,
K., Takeda, S., Fishel, R., Igarashi, K., Kamiya, K. DNA damage-dependent acetylation and
ubiquitination of H2AX enhances chromatin dynamics (2007). Mol. Cell. Biol. 27: 7028-40.
4. Dohi, Y., Ikura, T., Hoshikawa, Y., Katoh, Y., Ota, K., Nakanome, A., Muto, A., Omura, S., Ohta,
T., Ito, A., Yoshida, M., Noda, T., Igarashi, K. Bach1 inhibits oxidative stress-induced cellular
senescence by impeding p53 function on chromatin (2008). Nat. Struct. Mol. Biol. 15. 1246-54.
Late Effects Studies
(Laboratory of DNA Damage Signaling)
Human genome is under constant threat of DNA damage inflicted by exogenous (i.e. ionizing irradiation) or endogenous (i.e.
oxygen radical) agents. All cells are equipped with DNA damage signaling network to cope with this. We are studying molecular
mechanisms in the hereditary disorders, such as Fanconi anemia or familial breast cancer, which have defects in the network.
Minoru Takata, M.D., Ph.D.
Professor
❶
●
❷
●
Genome stability is crucial for maintaining integrity
of the organism, and therefore all cells have elaborate
systems to prevent, repair, or tolerate endogenous or
exogenous DNA damage. In higher organisms, loss
of the DNA damage signaling network often leads
to cancer predisposition as well as impaired stem
cell proliferation. A rare hereditary disorder Fanconi
anemia (FA) is a prototype of such conditions. 13
genes have been implicated in FA, while mutation
carriers of three FA genes develop familial breast
❸
●
cancer.
We are trying to elucidate regulatory mechanisms
and effecter function of genes involved in FA
and familial breast cancer. In response to DNA
damage, the key factors FancD2 and FancI are
monoubiquitinated by a multi-subunit ubiquitin E3
ligase, consisting of at least ten proteins known as the
FA core complex. In turn, FancD2 and FancI are both
targeted to chromatin and form colocalizing foci, and
function in DNA repair together with downstream ❶ Co-localization of the core complex component FANCC and FANCD2.
❷ The phospho-mimic mutant of FANCI (Dx6) induced focus formation in a DNA damagemolecule FancJ helicase. We have recently found that
independent manner.
phosphoryation of FancI serves as a molecular switch ❸ Member of the laboratory.
to trigger monoubiquitinaion of FancD2. Now we
are focusing on (1) how FancI is phosphorylated, (2)
chromatin targeting mechanisms of FancD2, (3) the
effecter function mediated by FancD2 and FancJ, (4)
a role of FancJ in chromosome translocation.
Recent Publications
Late Effects Studies
Professor : Minoru Takata, M.D., Ph.D.
Associate
Professor : Masamichi Ishiai, Ph.D.
TEL
: +81-75-753-7563
FAX
: +81-75-753-7564
e-mail
: [email protected]
URL
: http://www.rbc.kyoto-u.ac.jp/top.html
Kyoto University
1. Takata M, Ishiai M, Kitao H. The Fanconi anemia pathway: Insights from somatic cell genetics
using DT40 cell line. Invited review. Mutat Res. 2009 Jul 31;668(1-2):92-102.
2. Ishiai M, Kitao H, Smogorzewska A, Tomida J, Kinomura A, Uchida E, Saberi A, Kinoshita
E, Kinoshita-Kikuta E, Koike T, Tashiro S, Elledge SJ, & Takata M. FANCI phosphorylation
functions as a molecular switch to turn on the Fanconi anemia pathway. Nat Struct Mol Biol. 2008
Nov;15(11):1138-46.
3. Ling C, Ishiai M, Ali AM, Medhurst AL, Neveling K, Kalb R, Yan Z, Xue Y, Oostra AB, Auerbach
AD, Hoatlin ME, Schindler D, Joenje H, de Winter JP, Takata M, Meetei AR, Wang W. FAAP100 is
essential for activation of the Fanconi anemia-associated DNA damage response pathway. EMBO
J. 2007 Apr 18;26(8):2104-14.
4. Kitao H, Yamamoto K, Matsushita N, Ohzeki M, Ishiai M, Takata M. Functional interplay between
BRCA2/FANCD1 and FANCC in DNA repair. J Biol Chem. 2006 Jul 28;281(30):21312-20.
5. Matsushita N, Kitao H, Ishiai M, Nagashima N, Hirano S, Okawa K, Ohta T, Yu DS, McHugh
PJ, Hickson ID, Venkitaraman AR, Kurumizaka H, Takata M. A FancD2-Monoubiquitin Fusion
Reveals Hidden Functions of Fanconi Anemia Core Complex in DNA Repair. Mol Cell. 2005 Sep
16;19(6):841-7.
6. Hirano S, Yamamoto K, Ishiai M, Yamazoe M, Seki M, Matsushita N, Ohzeki M, Yamashita
YM, Arakawa H, Buerstedde JM, Enomoto T, Takeda S, Thompson LH, Takata M. Functional
relationships of FANCC to homologous recombination, translesion synthesis, and BLM. EMBO J.
2005 Jan 26;24(2):418-27.
Genome Dynamics
(Laboratory of Genome Dynamics)
Current work in radiation biology, which started from the identification and isolation of genes responsible for radiation-sensitive
human diseases, has revealed that the proteins which have a role in cellular radiation responses are also involved in a variety
of important biological processes such as homologous recombination, DNA replication, cell cycle checkpoints, telomere
maintenance. Our group is pursuing studies of repair gene networks starting with a NBS1 gene found to be responsible for a
radiation sensitive disease. We would like to welcome serious students to join us if they are interested in helping to develop this
new field of modern radiation biology.
Kenshi Komatsu, Ph.D.
Professor
❶
●
❸
●
Our group is focusing on the biology of one protein
in order to understand its multifunctional behavior
in responding to DNA double-strand breaks, and the
relationship of these breaks to a variety of pathways
in living cells. Nijmegen breakage syndrome,
characterized by a high sensitivity to DNA doublestrand breaks and a predisposition to cancer, is a rare
recessive genetic disease. NBS1, the underlying gene
❷
responsible for this disease, initiates homologous ●
recombination repair in DNA by recruiting the
Mre11/Rad50 nuclease to sites of DNA damage.
NBS1 is also involved in cell growth and division
through its regulation of S-phase and G2-phase
checkpoints. Since damage repair is coordinated
with cell growth, communication between DNA
repair and checkpoint regulation functions is being
investigated by the analysis of histone modifications.
This modification process appears to be a unifying
agent for the understanding of genome network
function. Homologous recombination, inititated
by the NBS1 gene, is an essential event for repair ❶ NBS1, the product of the gene underlying the Nijmegen breakage syndrome, contains
three functional regions: the forkhead associated (FHA) domain and CA1 C-terminus
and meiotic recombination, and is also essential for
(BRCT) domain at the N-terminus, several SQ motifs (consensus phosphorylation sites
the development of recombinant proteins, and thus
by ATM and AT kinases) at a central region and MRE11-binding region at the C-terminus.
another goal of our work is to understand the multiple
The orthologs of NBS1 have not been identified in prokaryotes or archaebacteria,
pathways involved in homologous recombination
suggesting that this protein, especially the N-terminus, is unique to eukaryotic cell
and its regulation. Biological phenomena in
functions.
living cells cannot be studied today by assigning ❷ NBS1 forms a multimeric complex with hMRE11/hAD50 nuclease at the C-terminus and
recruits or retains them at the vicinity of sites of DNA damage by direct binding to histone
each problem into a specific research area, and
H2AX, which is phosphorylated by ATM in response to DNA damage. Thereafter, the
most problems studied today will be of interest
NBS1-complex proceeds to rejoin double-strand breaks predominantly by homologous
or relevance to several different fields. Modern
recombination repair and this process collaborates with cell-cycle checkpoints to facilitate
radiation biology is multidisciplinary area. Our goal
DNA repair. The immunofluorescent staining indicated co-localization of gamma-H2AX
foci and hME11 foci formation in wild type cells (low panel), but hMRE11 protein was
of education is to support young scientists who take
confined in cytoplasm in NBS cells (upper right).
a multidisciplinary approach, and try to understand
❸ Laboratory staffs
real biological events with the tools and methods
available from a number of modern fields.
Genome Dynamics
Professor : Kenshi Komatsu
Assistant
Professor : Junya Kobayashi
TEL
: +81-75-753-7550
FAX
: +81-75-753-7564
e-mail
: [email protected]
URL
: http://www.rbc.kyoto-u.ac.jp/Genome/
index.html
Recent Publications
1. S. Matsuura, H. Tauchi, A. Nakamura, N. Kondo, S. Sakamoto, S. Endo, D. Smeets, B. Solder, B.
H. Belohradsky, V. M. D. Kaloustian, M. Oshimura, M. Isomura, Y. Nakamura, K. Komatsu (1998)
Positional cloning of the gene for Nijmegen breakage syndrome. Nature Genet., 19: 179-181.
2. H. Tauchi, J. Kobayashi, K. Morishima, D. C. van Gent, T. Shiraishi, N. S. Verkalk, D. van Heems,
E. Itoh, A. Nakamura, E. Sonoda, M. Takata, S. Takeda, S. Matsuura, K. Komatsu (2002) Nbs1 is
essential for DNA repair by homologous recombination in higher vertebrate cells, Nature, 420:9398.
3. J. Kobayashi, H. Tauchi, S. Sakamoto, A. Nakmaura, K. Morishima, S. Matsuura, T. Kobayashi, K.
Tamai, K. Tanimoto, K. Komatsu (2002) NBS1 localizes to gamma-H2AX foci through interaction
with the FHA/BRCT domain. Curr. Biol., 12:1846-1851.
- Institute for Chemical Research
Chemical Biology
Division of Biochemistry
In human history, small organic molecules have been utilized for improving human health and for revealing secrets of life.
Discovery or design of small organic molecules with unique biological activity permits small-molecule-initiated exploration
of biology and further understanding of human diseases. Our laboratory has been discovering small organic molecules that
modulate transcription or differentiation to use them as tools to explore biology. Such chemistry-initiated biology is recently
called chemical biology, an emerging field of biology and medical sciences. Although our chemical biology is a basic one, it may
“catalyze” future drug discovery.
Motonari Uesugi, Ph.D.
Professor
Our laboratory attempts to make biomedical
discoveries through the discovery, synthesis, and
utilization of bioactive small organic molecules.
Such small-molecule-initiated biology may
provide a new avenue to a better understanding
of biological events or diseases, and recently
called chemical biology or chemical genetics. Our
chemical biology investigation tackles a number of
biomedical problems, including gene expression,
cell differentiation, gene manipulation, cancer, and
metabolic diseases. We hope to provide fresh insights
into the understanding of these biological processes
or diseases.
Our laboratory also provides rigorous researchbased training for graduate students and
postdoctoral fellows in the fields of molecular
biology, biochemistry, organic chemistry, analytical
chemistry, and cell biology, and the investigators
in the laboratory have distinct backgrounds from
each other’s. Discussion with the investigators with
different backgrounds in the laboratory usually leads
to the initiation of our research projects.
Recent Publications
Chemical Biology
Professor : Motonari Uesugi
Assistant
Professor : Yoshinori Kawazoe, Hiroki Shimogawa
TEL
: +81-774-38-3225
FAX
: +81-774-38-3226
e-mail
: [email protected]
URL
: http://www.scl.kyoto-u.ac.jp/~uesugi/
Kyoto University
1. Uesugi, M., Nyanguile, O., Lu, H., Levine, A. J., Verdine, G. L. Induced alpha-helix in the VP16
activation domain upon binding to a human AF.
Science 277, 1310-1313 (1997).
2. Asada, S., Choi, Y., Yamada, M., Wang, S., Hung, M., Qin, J., Uesugi, M. External control of Her2
expression and cancer cell growth by targeting a Ras-linked coactivator. Proc. Natl. Acad. Sci. USA
99, 12747-12752 (2002).
3. Choi, Y., Kawazoe, Y., Murakami, K., Misawa, H., Uesugi, M. Identification of bioactive
molecules by adipogenesis profiling of organic compounds. J. Biol. Chem. 278, 7320-7324 (2003).
4. Shimogawa, H., Kwon, Y., Mao, Q., Kawazoe, Y., Choi, Y., Asada, S., Kigoshi, H., Uesugi, M. A
wrench-shaped synthetic molecule that odulates a transcription factor-coactivator interaction J. Am.
Chem. Soc.126, 3461-3471 (2004).
5. Kwon, Y., Arndt, H., Mao, Q., Choi, Y., Kawazoe, Y., Dervan, P. B., Uesugi, M. Small molecule
transcription factor mimic J. Am. Chem. Soc. 126, 15940-15941 (2004).
6. Choi, Y., Shimogawa, H., Murakami, K., Ramdas, L., Zhang, W., Qin, J., Uesugi, M. Chemical
genetic identification of the IGF-linked pathway that is mediated by STAT6 and MFP2 Chemistry
& Biology, 13, 241-249 (2006).
- Institute for Frontier Medical Sciences
Field of Biological Function
Our research focuses on the quality control mechanism of proteins in mammalian cells. Folding of newly synthesized proteins
are assisted by molecular chaperones, and polypeptides that failed to obtain their native conformations are eventually degraded
intracellularly. Under stress conditions such as heat shock and endoplasmic reticulum (ER) stress, polypeptides are denatured
and prone to aggregate, which causes cellular insults. Cells are equipped with a sophisticated mechanism of quality control of
proteins to maintain cellular functions and to prevent cell damage.
We are working on the molecular mechanism
of ERQC (ER quality control) and ERAD (ERassociated degradation) in mammals. Nascent
polypeptides attain their native conformations
by the assistance of molecular chaperones and
folding enzymes in the ER, and sorted further into
the secretory pathway. When proteins misfold
irreversibly in the ER during the synthesis or
by ER stress, they are recognized as terminally
misfolded, and retrotranslocated to the cytosol
through the unidentified dislocation channel.
After ubiquitylation, misfolded polypeptides are
degraded by the cytosolic proteasome. Most proteins
synthesized in the ER are N-glycosylated, and
ERQC of proteins also depends on the processing
of N-glycans, which act as tags recognized by ER
lectins. These mechanisms are conserved from yeast
to mammals. Recently, many works have clarified
the importance of ERAD of misfolded proteins
and the disruption of ERQC in genetic diseases
and neurodegenerative disorders. Our study will be
performed from a broad point of view.
❶
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❷
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❶Q u a l i t y c o n t r o l
mechanism in the ER
Fo l d i n g o f t h e n ew l y
synthesized proteins is
assisted by molecular
chaperones and folding
enzymes in the ER,
and only proteins with
correct conformations
are sorted further into
the secretory pathway.
When the proteins failed
to fold correctly, they are
retained in the ER and
eventually degraded by
ERAD.
❷ Involvement of N-glycans
in the ER quality control
Most of the proteins
synthesized in the
ER are modified with
N-glycans, and through
recognition by specific
lectins, oligosaccharides
act as glycan signals
for the quality control of
glycoproteins.
❸ Intracellular localization
of EDEM3
EDEM3 (Endoplasmic
reticulum-degradation
enhancing alphamannosidase-like
protein-3) localizes in the
ER.
Recent Publications
Associate
Professor : Nobuko Hosokawa
TEL
: +81-75-751-3849
FAX
: +81-75-751-4646
e-mail
: [email protected]
URL
: http://www.frontier.kyoto-u.ac.jp/
bf01/index-e.html
1. The role of MRH domain-containing lectins in ERAD.
Hosokawa N, Kamiya Y, Kato K. Glycobiology, in press (2010)
2. EDEM1 accelerates the trimming of alpha1,2-linked mannose on the C branch of N-glycans.
Hosokawa N, Tremblay LO, Sleno B, Kamiya Y, Wada I, Kato K, Nagata K, and Herscovics A.
Glycobiology: in press (2010)
3. Human OS-9, a lectin required for glycoprotein endoplasmic reticulum-associated degradation,
recognizes mannose-trimmed N-glycans.
Hosokawa N, Kamiya Y, Kamiya D, Kato K, and Nagata K. J. Biol. Chem.: 284, 17061-17068
(2009)
4. Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L
ubiquitin ligase complex and BiP.
Hosokawa N, Wada I, Nagasawa K, Moriyama T, Okawa K, and Nagata K. J. Biol. Chem.: 283,
20914-20924 (2008)
5. Simultaneous induction of the four subunits of TRAP complex by ER stress accelerates ER
degradation.
Nagasawa K, Higashi T, Hosokawa N, Kaufman R J, Nagata K. EMBO Rep.: 8, 483-489 (2007)
Our goal is to analyze the protein complex in the cell. We are analyzing transcription machinery that is most important and
complicated system. To analyze the transcription machinery as a model of in vivo analysis, we are trying to develop a new
technology, which is efficient in the cell.
All phenomenon in the living cells are under the
control of transcription. To understand the whole
view of transcription machinery, we focused on the
basal transcription. Transcription is a new and old
problem in the lifescience field. A lots of scientists
were tried to clarify the transcription in vitro. To
understand the real reaction in the cell is still in
the dark. To overcome the technical difficulties,
we introduced a new technology RNA aptamer.
This is an innovative technology to use an RNA as
an analytical tool.RNA aptamer can bind to intracellular molecule including a protein using their
tertiary structure. This molecule can penetrate into
the cell to take full advantage of its compactness and
can behave like as antibodies in the cell. The utility
of this molecule is not only the analytical tool in the
molecular biology, and is with great potentialoties as
a therapeutic molecule. To apply the advantages of
this molecule in the field of medical sciences and life
sciences, we are developing software and hardware
of application.
❶
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❶Determination
of binding site of
RNA aptamer and
expected structure
Basal transcription
factors on the gene.
❷RNA aptamer
prevents the binding
of factors and inhibits
the for mation of
transcription.
❷
●
Recent Publications
Senior
Lecturer : Kazunori Hirayoshi
TEL
: +81-75-751-3840
FAX
: +81-75-751-4646
e-mail
: [email protected]
Kyoto University
1. Chiba,Y et al.(2005)Cultured murine dermal fibloblast-like cells from senescence-accelerated
mice as in vitro models for higher oxidative stress due to mitochondrial alterations. J. Gerontol.
A.Biol. Sci. Med. Sci. 60, 1987-1098
2. Li Z.Y. et al.(2000) Expression of N-deacetylase/sulfotransferase and 3-O-sulfotransferase in rat
alveolar type II cells.Am. J. Physiolo. Lung Cell Mol. Physiol.279,L292-301.
3. Law,A. et al.(1998)Direct cloning of DNA that interacts in vitro with a specific protein application
to RNA polymerase II and sites of pausing in Drosophila. Nucleic Acids Res. 26, 919-924.
4. Shopland L. S. et al.(1995)HSF access to heat shock elements in vivo dependends critically on
promoter architecture defined GAGA factor, TFIID, and RNA polymerase II binding sites.9, 27562769.
Our Department is studying how the immune system controls physiological and pathological immune responses. Our main
interest is in understanding the mechanism of immunologic unresponsiveness to self-constituents (i.e., immunologic selftolerance) to determine the cause and mechanism of autoimmune disease, to develop the ways to provoke effective tumor
immunity, and to establish stable immunologic tolerance to organ-transplants.
Shimon Sakaguchi, M.D., Ph.D
Professor
The aim of this department in education and research
is to provide a good opportunity for students to learn
immunology and help them establish themselves
as researchers in immunology and medicine. Our
research is currently focused on understanding the
mechanisms of immunologic self-tolerance (i.e.
immunological unresponsiveness of the normal
immune system to normal self-constituents). We
specifically study: (i) the cellular and molecular basis
of immunologic self-tolerance and the etio-pathology
of autoimmune disease; (ii) the strategy for eliciting
effective immune responses to autologous tumor
cells, or inducing immunologic tolerance to organ
transplants, by manipulating the mechanism of
immunologic self-tolerance; and (iii) the cause and
pathogenetic mechanism of rheumatoid arthritis by
analyzing an animal model newly established in our
laboratory.
❶
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❶ Defects in immune regulation mediated
by regulatory T cells cause autoimmune
gastritis accompanying anti-parietal cell
autoantibody, autoimmune thyroiditis,
and insulitis of Langerhans’ islets of the
pancreas as observed in human type 1
diabetes.
❷ Regulatory T cells control hazardous
autoimmune T cells, thereby preventing
autoimmune disease.
Recent Publications
Professor : Shimon Sakaguchi
TEL
: +81-75-751-3851
FAX
: +81-75-751-3820
e-mail
: [email protected]
URL
: http://www.frontier.kyoto-u.ac.jp/bf03/
1. Sakaguchi, S.: Naturally arising CD4+ regulatory T cells for immunologic self-tolelance and
negative control of immune responses. Ann. Rev. Immunol. 22:531-562, 2004.
2. Sakaguchi1, N., Takahashi1, T., Hata, H., Nomura, T., Tagami, T., Yamazaki, S., Sakihama, T.,
Matsutani, T., Negishi, I., Nakatsuru1, S., and Sakaguchi, S.: Altered thymic T-cell selection due to
a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 426:454-60, 2003.
3. Hori, S., Nomura, T., and Sakaguchi, S.: Control of regulatory T cell development by the
transcription factor Foxp3. Science. 299: 1057-1061, 2003.
4. Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., and Sakaguchi, S.: Stimulation of
CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nature
Immunol. 3: 135-142, 2002.
To understand the mechanisms regulating temporal and spatial generation of stem and progenitor cells within organs, we focus
our analysis on microenvironmental niches for hematopoietic stem cells (HSCs) and progenitors and requisite signals provided
by the niches, including the chemokine CXCL12 (SDF-1) and its receptor CXCR4. We utilize various techniques based on
molecular biology, cellular biology, developmental biology and histology. The students are trained to be an excellent scientist,
doing the research with us.
Takashi Nagasawa, M.D., Ph.D.
Professor
Chemokines are a large family of small structurally
related cytokines that are thought to regulate cell
trafficking and utilize seven- transmembrane
spanning G-protein-coupled receptors (GPCR). We
identified CXC chemokine ligand 12 (CXCL12),
also known as stromal cell-derived factor (SDF)1 as pre-B-cell growth stimulating factor and
found that CXCL12 and its primary receptor
CXCR4 are essential for hematopoiesis, including
colonization of bone marrow by hematopoietic stem
cells (HSCs) during ontogeny, maintenance of the
HSC pool in adult bone marrow and development
of B lymphocytes and plasmacytoid dendritic
cells (pDCs) as well as cardiogenesis and organ
vasculalization during ontogeny (4,5). Recently,
we have identified a small population of nonhematopoietic cells expressing high amounts of
CXCL12, termed CXCL12-abundant reticular
(CAR) cells with long processes. We have revealed
that CAR cells are scattered throughout bone marrow
and that most HSCs, early B cell precursors, the
end-stage B lymphocyte plasma cells and pDCs
are attached to the processes of CAR cells and that
CAR cells are adipo-osteogenic progenitors, which
function as the special microenvironments, termed
‘niches’ for HSCs and hematopoietic progenitors (13). We educate students in research, reading of papers
and discussion.
❶
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●
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❶ CXCL12-CXCR4 signaling is essential for homing of HSCs and primordal germ cells
(PGCs) to the bone marrow and gonads, respectively during ontogeny and might be
involved in cancer metastasis, colonization of cancer stem cells in the adult.
❷ CAR cells, expressing high levels of CXCL12 have long processes.
❸ Model of niches for HSCs and lympho-hematopoietic cells.
❹ Laboratory members.
Recent Publications
Professor : Takashi Nagasawa
Assistant
Professor : Tatsuki Sugiyama
TEL
: +81-75-751-4100
FAX
: +81-75-751-4820
e-mail
: [email protected]
URL
: http://www.frontier.kyoto-u.ac.jp/se03/
index-e.html
Kyoto University
1. Omatsu, T., Sugiyama, T., Kohara, H., Kondoh, G., Fujii, N., Kohno,, K., *Nagasawa, T. The
Essential Functions of Adipo-osteogenic Progenitors as the Hematopoietic Stem and Progenitor
Cell Niche.
Immunity 33; 387-399, 2010.
2. Sugiyama, T., Kohara, H., Noda, M., and *Nagasawa, T. Maintenance of the Hematopoietic Stem
Cell Pool by CXCL12-CXCR4 Signaling in Bone Marrow Stromal Cell Niches.
Immunity 25; 977-988. 2006.
3. Tokoyoda, K., Egawa, T., Sugiyama, T., Byung-I1 Choi and *Nagasawa, T. Cellular niches
controlling B lymphocyte behavior within bone marrow during development.
Immunity 20; 707-718, 2004
4. Tachibana, K., Hirota, S., Iizasa, H., Yoshida, H., Kawabata, K., Kataoka, Y., Kitamura, Y.,
Matsushima, K., Yoshida, N., Nishikawa, S., Kishimoto, T., and *Nagasawa, T. The chomokine
receptor CXCR4 is essential for vascularization of the gastrointestinal tract.
Nature 393: 591-594, 1998.
5. *Nagasawa, T., Hirota, S., Tachibana, K., Takakura, N., Nishikawa, S.-I., Kitamura, Y.,Yoshida, N.,
Kikutani, H., and Kishimoto, T. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in
mice lacking the CXC chemokine PBSF/SDF-1.
Nature 382: 635-638, 1996
Field of Tissue Engineering
With the advent of the aging society, movement disorder and dementia are becoming major targets in mordern health care and
medicine. Our research efforts are focused on the elucidation of molecular mechanisms underlying formation and regeneration
of tissues in locomotive organs such as bone, cartilage, and tendon/ligaments with the molecular approaches based on
developmental biology and cell biology.
Yuji Hiraki, Ph.D.
Professor
❶
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In general, mesenchymal tissues contain a welldeveloped network of capillaries. However, cartilage
is resistant to vascular invasion from surrounding
tissues and is usually kept avascular except for the
vascular invasion into cartilage during endochondral
bone formation. Similarly, tendons and ligaments
are known to be hypovascular. In our laboratory, we
identified chondromodulin-I for the first time as a
tissue-specific angiogenesis inhibitor in cartilage.
Molecular cloning of the chondromodulin-I related
gene enabled us to identify another tissue-specific
anti-angiogenic molecule Tenomodulin, which is
specifically expressed in tendons and ligaments. We
think it important to understand what is the nature of
hypovascularity in mesenchymal structures and how
it plays a role in the body during development and
regeneration of musculoskeletal organs.
❷
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❸
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Our current research efforts are focused on the
following studies: 1) mechanism of replacement
of cartilage by bone during endochondral bone
formation; 2) identification of novel genes associated
with chondrogenic differentiation by global analysis
of gene expression; 3) mechanism underlying
regeneration of articular cartilage; 4) molecular
mechanism of tendon/ligament development; 5)
action mechanisms of tissue-specific anti-angiogenic
❶ Differentiation of mesenchymal stem cells
factors and their therapeutic applications for
❷ Fish facility for Medaka and Zebrafish.
angiogenic diseases.
Medaka and zebrafish are excellent model organisms for elucidating developmental
processes due to the transparency of embryos. Current projects in our laboratory are
to reveal role of chondromodulin-I, cartilage-derived angiogenesis inhibitor, in vascular
development and molecular mechanism of cartilage development.
❸ Laboratory members
Recent Publications
Professor : Yuji Hiraki
Associate
Professor : Chisa Shukunami
TEL
: +81-75-751-4608
FAX
: +81-75-751-4633
e-mail
: [email protected]
URL
te01/index-j.htm
1. Miura S, Mitsui K, Heishi T, Shukunami C, Sekiguchi K, Kondo J, Sato Y, Hiraki Y (2010)
Impairment of VEGF-A-stimulated lamellipodial extensions and motility of vascular endothelial
cells by Chondromodulin-I, a cartilage-derived angiogenesis inhibitor. Exp Cell Res, 316: 775-788
2. Takimoto A, Nishizaki Y, Hiraki Y, Shukunami C (2009) Differential actions of VEGF-A isoforms
on perichondrial angiogenesis during endochondral bone formation. Dev Biol 322: 196-211
3. Shukunami C, Takimoto A, Miura S, Nishizaki Y, Hiraki Y (2008) Chondromodulin-I and
tenomodulin are differentially expressed in the avascular mesenchyme during mouse and chick
development. Cell Tissue Res 332: 111-122
4. Mori H, Shukunami C, Furuyama A, Notsu H, Nishizaki Y, Hiraki Y (2007) The immobilization of
bioactive FGF-2 into cubic proteinous micro-crystals (Bombyx mori cypovirus polyhedra) that are
insoluble in a physiological cellular environment. J Biol Chem 282: 17289-17296
5. Shukunami C, Takimoto A, Oro M, Hiraki Y (2006) Scleraxis positively regulates the lineagespecific expression of tenomodulin, a marker of tenocytes. Dev Biol 298: 234-247
Field of Regeneration Control
This laboratory analyzes molecular and cellular mechanisms to control function of stem cells and differentiation of mammalian
germ cells by using various mouse strains. Particular attention is paid to the development of embryonic germ cells and
spermatogenic cells in testes, as well as pluripotent embryonic stem cells. Also, we are the only group in Japan carrying out the
establishment and distribution of human embryonic stem cell lines. So far, we have established and characterized five human ES
cell lines, and we have distributed cell lines to about 50 research projects since March 2004.
Norio Nakatsuji, D.Sc.
Professor
❶
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The succession between germ cells and pluripotent
cells are fundamentals for ontogeny of individuals
and continuity through generations. Molecular
mechanisms underlying the germ-line cells serve
as basal states for the derivation of somatic cell
lineages. We aim to elucidate such basic molecular
systems underlying in the germ-line cells, and are
currently focusing on cytoplasmic RNP structures
in the germ cells, called nuage or germ granules,
through the identification and functional analyses
of the specific components. We have shown that
(1) proteins containing multiple Tudor domains,
❷
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TDRD1/MTR1, TDRD6 and TDRD7/TRAP in
mice specifically localize to germ granules/nuage
during spermatogenesis, (2) a single Tudor domain
is sufficient for the localization to germ granules/
nuage, but its over-expression causes meiotic defect
during spermatogenesis, (3) spliceosomal complex
snRNPs accumulate to germ granules/nuage during
spermatogenesis and form complex with TDRD1, (4)
mice homozygous for a targeted mutation of Tdrd1
are male-sterile, and (5) the localization of TDRD1
to germ granules/nuage is under the control of Mvh
activity. Further analyses on these mammalian tudorrelated genes are in progress. We are also trying to
isolate specific components of germ granules/nuage
by proteomics/transcriptome analyses. Also, we
❸
●
are the only group in Japan carrying out important
activities of the establishment and distribution
of human embryonic stem cell lines. We have
obtained the approval and national grants to produce
human ES cell lines in April 2002. So far, we have
established and characterized five human ES cell
lines (KhES-1, -2, -3,-4, -5). We have distributed cell
lines to about 50 research projects since March 2004.
Such distributed human ES cells will be used for
many aspects of the biomedical research.
Recent Publications
Professor : Norio Nakatsuji
Senior
Lecturer : Eihachiro Kawase
Assistant
Professor : Shinichiro Chuma
TEL
: +81-75-751-3821
FAX
: +81-75-751-3890
e-mail
: [email protected]
URL
rc01/index-j.htm
Kyoto University
❶ Ribonucleoprotein-rich granules
in the cytoplasm of germ cells,
showing specific localization of
one of the components (green).
❷ Ribonucleoprotein-rich granules
in the cytoplasm of germ cells,
showing specific localization of
one of the components (green).
❸ Members
1. Hosokawa, M., Shoji, M., Kitamura, K,. Tanaka, T., Noce, T., Chuma, S., Nakatsuji, N. Tudorrelated proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: Domain composition, intracellular
localization, and function in male germ cells in mice. Dev. Biol. 301, 38-52 (2007).
2. Nakatsuji, N., Nakajima, F., Tokunaga, K. HLA-haplotype banking and iPS cells. Nature
Biotechnol. 26, 101-106 (2008).
3. Miyazaki T, Futaki S, Hasegawa K, Kawasaki M, Sanzen N, Hayashi M, Kawase E, Sekiguchi K,
Nakatsuji N, Suemori H. Recombinant human laminin isoforms can support the undifferentiated
growth of human embryonic stem cells. Biochem Biophys Res Commun. 375, 27-32 (2008).
4. Yamauchi, K., Hasegawa, K., Chuma, S., Nakatsuji, N. and Suemori, H. In vitro germ cell
differentiation from cynomolgus monkey embryonic stem cells. PLoS ONE 4, e5338 (2009).
5. Shoji, M., Tanaka, T., Hosokawa, M., Reuter, M., Stark, A., Kato, Y., Kondoh, G., Okawa, K.,
Chujo, T., Suzuki, T., Hata, K., Martin, S. L., Noce, T., Kuramochi-Miyagawa, S., Nakano, T.,
Sasaki, H., Pillai, R. S., Nakatsuji, N. and Chuma, S. The TDRD9-MIWI2 complex is essential for
piRNA-mediated retrotransposon silencing in the mouse male germline. Developmental Cell 17,
775-787 (2009).
Growth Regulation
Field of Regeneration Control
Cellular differentiation and tissue formation during development of muticellular organisms including human require cellcell communications and interactions. Investigations of our lab focus on molecular mechanisms that govern such cellular
interactions, which play roles in cellular differentiation, tissue formation, and organogenesis.
1)Molecular mechanisms of cellular differentiation and organogenesis of mesodermal tissues including skeletal muscle, heart,
and adipose tissue.
2)Myogenesis during development and regeneration, muscle stem cells
3)Roles of ADAM genes in organogenesis and diseases.
Atsuko Sehara-Fujisawa, Ph.D.
Professor
❶
●
■Topics of Our Research
Current topics of our research are on the roles of
ADAM proteases in organogenesis. Numerous
intercellular signaling molecules are generated
as membrane-anchored proteins, and they are
subjected to proteolytic processing to liberate their
extracellular domains (These phenomena is called
as ectodomain sheddings). Molecular bases that
regulate the ectodomain shedding processes are ●
❷
coming into focus since discovery of ADAM family
proteins that participate in the ectodomain shedding
through their protease domains. Our lab is one of
pioneer groups in the world who have identified
and investigated the roles and functions of ADAM
proteins in development. We found that Meltrin alpha
and beta, members of ADAM proteins, are involved
in the liberation of soluble ErbB ligands from
membrane-anchored growth factors. Meltrin alpha
play roles in myogenesis and adipogenesis while
❸
❹
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Meltrin beta is involved in neurogenesis and the ●
heart formation. Thus, metalloproteases of Meltrins
work as scissors to modulate intercellular signalings
necessary for organogenesis through generation
of soluble growth or differentiation factors from
membrane-anchored precursor molecules. Numerous
ADAM genes are found in human genome. We
hope to reveal significance of ectodomain sheddings ❶ (left panel) The meltrin alpha knockout mouse shows mild resistance to high fat-diet
induced obesity. (left panel) Meltrin beta is involved in the heart development.
mediated by ADAM proteases and their regulatory
❷ ADAM proteases work as scissors that generate soluble growth or differentiation factors
mechanisms in development and diseases.
from membrane-anchored precursor molecules.
❸ The onset of blood circulation. Live imaging of zebrafish embryos revealed the
synchronous onset of blood circulation. Protease activity of ADAM8 regulates the onset
of blood circulation by abrogation of blood-blood vessel adhesion
❹ Staffs and graduate students
Recent Publications
Department of Growth Regulation
Professor : Atsuko Sehara-Fujisawa
Assistant
Professor : Tomohiro Kurisaki, Atsuo Iida
TEL
: +81-75-751-3826
FAX
: +81-75-751-4642
e-mail
: [email protected]
URL
rc03/index-j.html
1. Sunadome, K., Yamamoto, T., Ebisuya, M., Kondoh, K., Sehara-Fujisawa., A., Nishida, E.. ERK5
Regulates Muscle Cell Fusion through Klf Transcription Factors. Dev. Cell, in press
2. Iida, A., Sakaguchi, K., Sato, K., Sakurai, H., Nishimura, D., Iwaki, A., Takeuchi, M., Kobayashi,
M., Misaki, K., Yonemura, S., Kawahara, A., and Sehara-Fujisawa, A.. Metalloprotease-Dependent
Onset of Blood Circulation In Zebrafish. Current Biol., 22;20(12):1110-6. (2010)
3. Wakatsuki, S., Yumoto, N., Komatsu, K., Araki, T., Sehara-Fujisawa, A.. : Roles of meltrin beta
/ADAM19 in progression of Schwann cell differentiation and myelination during sciatic nerve
regeneration. J Biol Chem. (2008)
4. Yumoto, N., Wakatsuki, S,. Kurisaki, T., Hara, Y., Osumi, N., Frisén, J., Sehara-Fujisawa, A.. :
Meltrin beta/ADAM19 interacting with EphA4 in developing neural cells participates in formation
of the neuromuscular junction. PLoS ONE, 3(10): e3322. (2008)
5. Weskamp, G., Ford, J.W., Sturgill, J., Martin, S.,Docherty, A., Swendeman, S., Broadway, N.,
Hartmann,D., Saftig, P., Umland, S., Sehara-Fujisawa, A., Black, R.A., Ludwig, A., Becherer,
J.D., Conrad, D.H. and Blobel, C.P. : ADAM10 is a principal ‘shedase’ of the low-affinity
immunoglobulin E receptor CD23. nature immunology, ;7(12):1293-1298. (2006)
Immunology
Fields of Regeneration Control
T cells develop in thymus and are main players in the field of the cellular immunity. Sub-lethal irradiation or administration
of chemical mutagens to mice causes them severe thymic atrophy. Later the thymus regenerates by the supply of stem cells
from bone marrow. However, thymic lymphoma often emerges during the process. We have been investigating the tumorigenic
differences for X-ray induced and ENU induced thymic lymphomas. We are also interested in unraveling the mechanism of T
cell receptor (TCR) beta chain gene rearrangement and are intensively analyzing the gene segments used for recombination in
the murine thymic lymphomas.
TCRbeta chain gene rearrangement is ordered; first,
D to J rearrangement occurs on both alleles, then,
one of the alleles initiates V to DJ rearrangement.
We have established a method to detect the V, D
and J segments recombined for TCRbeta chain
genes utilizing PCR. As shown in Figure, D to
J rearrangement yields two types of DJ alleles.
Molecular processes of how these two constructs
are made are poorly understood and even which
is dominantly formed has not been clearly shown.
Our recent analyses of two series of murine thymic
lymphomas have revealed the ratio of these two
DJ alleles. Moreover we have obtained the data
indicating that occurrences of V to DJ rearrangement
from each allele are not the same (Table). A T cell
expresses cell surface TCRbeta chains from a single
allele due to “allelic exclusion”. To achieve allelic
exclusion, it is assumed that V to DJ rearrangement
does not take place on both alleles simultaneously.
Our data, however, suggest it is not always applicable
that initiation of V to DJ rearrangement occurs on
one allele at a time. Elucidating the precise molecular
mechanisms of allelic exclusion is our final goal.
❶
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❶ Figure DJ alleles and VDJ alleles in TCRbeta locus
TCRbeta chain gene D to J rearrangement can generate two types of DJ alleles. Two
types of VDJ alleles from DJ (I) allele and one from DJ (II) allele can be formed by the
following V to DJ rearrangement.
❷ Table The occurrences of V to DJ rearrangement from DJ (I) / DJ (I) and DJ (II) / DJ (II)
allele
It was impossible to figure out separately the occurrences for alphabeta T cells based on
the other group’s data.
Recent Publications
1. Ikawa, T., Fujimoto, S., Kawamoto, H., Katsura, Y. and Yokota, Y. (2001) Commitment to natural
Immunology
killer cells requires the helix-loop-helix inhibitor Id2. Proc. Natl. Acad. Sci. USA. 98:5164-6169.
2. Kawamoto, H., Ohmura, K. Fujimoto, S., Lu, M., Ikawa, T. and Katsura, Y. (2003) Extensive
Assistant
proliferation of T cell lineage-restricted progenitors in the thymus: an essential process for clonal
Professor : Shinji Fujimoto
expression of diverse T cell receptor beta chains. Eur. J. Immunol. 33:606-615.
TEL
: +81-75-751-3845
3. Fujimoto, S., Ikawa, T., Kina, T. and Yokota, T. (2007) Forced expression of Id2 in fetal thymic T
FAX
: +81-75-751-4648
cell progenitors allows some of their progeny to adopt NK cell fate. Int. Immunol. 19:1175-1182.
e-mail
: [email protected]
4. Tokuriki, A., Iyoda, T., Inaba, K., Ikuta, K., Fujimoto, S., Kumakiri, M. and Yokota, T. (2009) Dual
URL
: http://www.frontier.kyoto-u.ac.jp/rc04/
role for Id2 in chemical carcinogen-induced skin tumorigenesis. Carcinogenesis 9:1645-1650.
Kyoto University
Tissue Regeneration
Field of Clinical Application
“All research should stem from clinical diseases.” is the basic concept of our department. This does not mean that all researchers
should have a medical background, but that all researches should be designed based on the pathological condition of target
diseases. Current medical procedures are requested to have molecular evidences to support their validity, as represented by
the term “Evidence Based Medicine”. Application of regenerative medicine should not be performed without comprehensive
understanding of biological events required for the process of regeneration for each tissue. Following these requirements, we are
investigating biological events during the regeneration of mesenchymal tissues to develop innovative therapeutic modalities.
Junya Toguchida, M.D., Ph.D.
Professor
The major role of mesenchymal tissues such as
bone, cartilage, and muscle is to compose the stature
specific for each multicellular organism, but they
also provide appropriate platforms for epithelial
tissues, creating the communication to receive and
transmit important signals for the maintenance of
homeostasis. Tissue regeneration is a biological
phenomenon accomplished by a number of players
including those who do not participate in the
development of each tissue, and the contribution
of each player is strictly regulated both in time
and place. It is a crucial process in multicellular
organisms for their survival, but also has a risk to
trigger the unregulated cell growth, which might
finally become neoplasms. Osteosarcoma, for
example, is one of malignant tumors of bone, and
created by the proliferation of tumor cells with
osteoblastic phenotype, which produced the bone
matrix. Pathological findings have several similar
features with the process of fracture healing. The
primary investigator of this field is an orthopaedic
surgeon dealing with the treatment of patients with
malignant mesenchymal tumors, and also engaging
in related basic researches, especially in genetic
alterations involved in carcinogenesis. One of unique
characters of our department is that researches for
regenerative medicine and for oncology, which
are tightly linked to each other, are investigated in
the same laboratory, even by a same researcher,
making it possible to share technologies and inspire
each other for developing a new cutting edge.
The establishment of immortalized mesenchymal
stem cell lines by oncogenic virus protein is one of
examples, and recent topic is the common features
of cancer stem cells and tissue stem cells. Since
2008, the clinical trial based on our previous animal
experiments are launched, which we believe is an
important step toward the realization of our aim
“bring the information “from bed side to bench
side”, and apply the new therapeutic modalities
“from bench side to bed side”. In addition, the PI has
joined the Center for iPS Research and Application
(CiRA) as a faculty, which will enlarge the field of
stem cell biology in our department. We are welcome
to cooperate with researchers who share our aim
irrespective of their background and also to have
young powers to join us.
Tissue Regeneration
Professor : Junya Toguchida
TEL
: +81-75-751-4134
FAX
: +81-75-751-4134
e-mail
: [email protected]
URL
ca02/index-j.htm
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❶ Induction of iPS cells from bone marrow stromal cells. Using bone marrow stromal cells
(B) from patients suffering bone and cartilage diseases with no appropriate treatments,
we are inducing iPS cells (A) to investigate the pathology and develop new treatments.
❷ Photo of members in the department
❸ Clinical trials of the application of mesenchymal stem cells for the treatment of
osteonecrosis of femoral head.
Recent Publications
1. Ikeguchi, R., et al. (2006) Regeneration of osteonecrosis of canine scapho-lunate using bone
marrow stromal cells: possible therapeutic approach for Kienböck disease. Cell Transplantation,
15:411-22.
2. Shibata KR et al. (2007) Expression of the p16INK4A gene is associated closely with senescence
of human mesenchymal stem cells, and potentially silenced by DNA methylation during in vitro
expansion. Stem Cells, 25:2371-82.
3. Toguchida J, Nakayama T. (2009) Molecular genetics of sarcomas: Applications to diagnoses and
therapy. Cancer Sci 100:1573-80.
4. Otsuka S, et al. (2009) PGE2 signal via EP2 receptors evoked by a selective agonist enhances
regeneration of injured articular cartilage Osteoarthritis Cartilage, 17:529-38.
5. Ito K, et al. (2009) A novel method to isolate mesenchymal stem cells from bone marrow in a
closed system using a device made by non-woven fabric. Tissue Eng Part C Methods, in press.
Organ Reconstruction
This department was founded immediately after the establishment of the Institute in 2002 by Professor Kazutomo Inoue who
moved, with his colleagues, from the First Department of Surgery, Kyoto University. Since then, we have been studying
regenerative medicine for endocrine and metabolic diseases including diabetes mellitus in relation with islet and pancreas
transplantation. The final goal of our study is to establish regenerative medicine for diabetes mellitus, which should be a safe and
effective therapy available whenever and wherever required for a growing number of diabetes patients world-wide. To this goal,
we are studying bio-artificial pancreas and other topics including cell therapy by various stem cells and novel transplantation
methods using biomaterials.
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This department has received undergraduate,
master’s and doctoral students as well as postdoctoral
fellows and foreign researchers. We have established
isolation method of rat and porcine islets and
successfully shown the efficacy of several macrodevices of bioartificial pancreas. In contrast to
micro-encapsulation that is irretrievable after
inplantation, macro-devices are retrievable and
exchangeable, which is important advantage
toward clinical application. In our past studies,
mesh-reinforced polyvinyl alcohol (PVA) tube ❶ Mesh-reinforced PVA-macroencapsulated islets (right: microscopic view of dithizonestaining)
and bag, rod-shaped device of agarose-based gel
and so on were investigated in allo- and xenogeneic situations. We have also shown that the
subcutaneous site pretreated for angiogenesis can
be successfully used for transplantation site of
these devices, leading to long-term normalization
of blood glucose levels in diabetic rodents.
Recently we developed a novel method to make
a sheet-shaped PVA-macroencapsulated islets by
a combination of the freezing technique of islets
and the phenomenon that PVA solution becomes
gel by freezing and thawing and are studying this
toward application to bigger animals and humans.
We are also studying chitosan-based biomaterials
for transplantation of islets or artificial beta-cells to
subcutaneous and miscellaneous sites. In addition,
we are studying various cell sources for cell therapy
of diabetes mellitus. These studies include beta-cell
differentiation form ES, iPS and other stem cells
using human artificial chromosome (collaborative
study with Professor Oshimura, Tottori University)
cell fusion between islet cells and mesenchymal stem
cells, showing several promising findings therapy.
Recent Publications
Associate
Professor
Assistant
Professor
TEL
FAX
e-mail
URL
: Shoichiro Sumi
: Yasumasa Shirouzu
: +81-75-751-4856 or 4848
: +81-75-751-4156
: [email protected]
: http://www.frontier.kyoto-u.ac.jp/ca03/
Kyoto University
1. Yang KC, Qi Z, Wu CC, Shirouza Y, Lin FH, Yanai G, Sumi S. The cytoprotection of chitosan
based hydrogels in xenogeneic islet transplantation: An in vivo study in streptozotocin-induced
diabetic mouse. Biochem Biophys Res Commun. 393(4): 818-823, 2010.
2. Qi Z, Shen Y, Yanai G, Yang K, Shirouzu Y, Hiura A, Sumi S. The in vivo performance of polyvinyl
alcohol macro-encapsulated islets. Biomaterials 31(14): 4026-4031, 2010.
3. Yang KC, Wu CC, Lin FH, Qi Z, Kuo TF, Cheng YH, Chen MP, Sumi S. Chitosan/gelatin hydrogel
as immunoisolative matrix for injectable bioartificial pancreas. Xenotransplantation. 15(6): 407416, 2008.
4. Sakata N, Gu Y, Qi M, Yamamoto C, Hiura A, Sumi S, Sunamura M, Matsuno S, Inoue K. Effect
of rat-to-mouse bioartificial pancreas xenotransplantation on diabetic renal damage and survival.
Pancreas. 32(3): 249-257, 2006.
5. Shirouzu Y, Gu Y, Koga M, Sakurai T, Qi M, Hiura A, Sumi S, Inoue K. Cold preservation of islets
in UW solution--with special reference to apoptosis. J Surg Res. 133(2):167-175, 2006.
We have devised a completely new approach so called “in situ Tissue Engineering” to the development of artificial organs. The
extracellular matrix (ECM) or reconstitutes the solid structure from the extracted collagen is employed as a scaffold, which after
implantation into the patients is used for the regeneration or re-differentiation of tissue. We have already carried out successful
trials at regenerating the trachea and peripheral nerves etc. with this method. Our pioneering work is expected to be a major area
of medical science for the coming generation.
We consider that mammals do not, in fact, lose
their ability to regenerate, and that the potential is
hidden by excessively rapid wound healing around
the failing tissues. In this sense, if we can provide
good conditions using a scaffold, we can induce this
hidden potential even in higher mammals. In tissue
engineering, three main components are used: (1)
cells, (2) a scaffold, and (3) growth factors. We have
advocated a new approach – in situ tissue engineering
– whereby tissue is made in the living body, rather
than in a culture bottle. To obtain the purified ECM,
cell components are completely removed from homo
or allo-organs. The solid structure is reconstituted
from the ECM and extracted collagen. Growth
factors are then applied to facilitate cell proliferation.
Then this ECM-collagen-growth factor composite
is implanted into the living body as a temporary
scaffold for new organ regeneration. Besides this,
bioabsorbable materials will also be applied instead
of purified ECM as a bulk structure for organ
regeneration. Both extracted collagen and growth
factors are should facilitate cell proliferation and cell
redifferentiation, leading to regeneration of organs
completely composed of cells derived from patients.
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❶ Generation of iPS(induced pluripotent stem) cells from canine fibroblasts
❷ Generation of neurons from canine iPS cells
❸ Regeneration of central nerves using a collagen scaffold and adipose-derived stromal
cells (ASCs)
Recent Publications
Associate
Professor : Tatsuo Nakamura
Part-time
Lecturer
: Katsumi Hayakawa, Keiji Shigeno,
Yuji Inada, Yoshio Hori,
Akeo Hagiwara
TEL
: +81-75-751-4149
FAX
: +81-75-751-4844
e-mail
: [email protected]
URL
: http://www.frontier.kyoto-u.ac.jp/ca04/
1. Shimada, H., Nakada, A., Hashimoto, Y., Shigeno, K., Shionoya, Y., Nakamura, T.: Generation
of canine induced pluripotent stem cells by retroviral transduction and chemical inhibitors. Mol
Reprod Dev. 77(1): 2 (2010)
2. Nakamura, T., Sato, T., Araki, M., Ichihara, S., Nakada, A., Yoshitani, M., Itoi, S., Yamashita, M.,
Kanemaru, S., Omori, K., Hori, Y., Endo, K., Inada, Y., Hayakawa, K.: In situ tissue engineering for
tracheal reconstruction using a luminar remodeling type of artificial trachea. J Thorac Cardiovasc
Surg. 138(4): 811-819 (2009)
3. Nakada, A., Fukuda, S., Ichihara, S., Sato, T., Itoi, S., Inada, Y., Endo, K., Nakamura, T.:
Regeneration of central nerves using a collagen scaffold and adipose-derived stromal cells. Cells
Tissues Organs. 190(6): 326-335 (2009)
4. Sato, T., Tao, H., Araki, M., Ueda, H., Omori, K., Nakamura, T.: Replacement of the left main
bronchus with a tissue-engineered prosthesis in a canine model. Ann Thorac Surg. 86(2): 422-428
(2008)
5. Kin, S., Hagiwara, A., Nakase, Y., Kuriu, Y., Nakashima, S., Yoshikawa, T., Sakakura, C., Otsuji,
E., Nakamura, T., Yamagishi, H.: Regeneration of skeletal muscle using in situ tissue engineering
on an acellular collagen sponge scaffold in a rabbit model. ASAIO J. 53(4): 506-513 (2007)
Nano Bioprocesses
Research Center for Nano Medical Engineering
Our laboratory is dedicated to methodology development for single-molecule observation and manipulation at nanometer
precisions in living cells. The development is carried out simultaneously with the application for the studies of nanobioprocesses occurring in living cells, in particular, signal transduction in the cell membrane and the formation and remodeling
of the neuronal network. The smooth liaison between physics/engineering and biomedicine is a key for our methodology
developments. On the basis of the knowledge of nano-bioprocesses learned in the cells (e.g., partitioning of the plasma
membrane into submicron compartments and transient formation of signaling platforms in the cell membrane) and the singlemolecule bionanotechnology developed here, we envisage the next-generation nanotechnology, regenerative medicine, and drug
discovery protocols.
Akihiro Kusumi, D. Sc.
Professor
The cell is surrounded by the cell membrane, and it is
responsible for exchanging information, energy, and
molecules with the outside world. Furthermore, 40%
of cellular reactions take place in the membrane, and
30% of energy is stored in a form of the concentration
gradient across the membrane. These functions are
carried out by biomolecular nanosystems, but how
exactly they are done is unknown. As described at
the end of this part, these membranes have incredibly
peculiar structures, and the cell appears to make the
cell membrane work by taking advantage of the very
peculiar structural features of the cell membrane.
We at the Kusumi laboratory are trying to understand
the basic mechanisms for the function of the cell
membrane at a very fundamental level. One of the
most important features of our projects is to develop
and apply single-molecule tracking/manipulation
techniques (single-molecule nanobiotechnology) for
the studies of living cells.
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Our study is based on a hypothesis that “three
fundamental physical properties of the cell
membrane are essentially responsible for its
function”. They are:
(1) its low (two) dimensionality greatly facilitates
molecular collisions,
(2) molecular complexes and micro(nano)domains
with various sizes and lifetimes continually form and
disintegrate, and
(3) the cell membrane is partitioned into many
small compartments due to the presence of the
actin-based membrane skeleton fence and anchored
transmembrane protein pickets aligned along the
membrane skeleton.
In our laboratory, we hope to better define these
three properties, and at the same time, to understand
how these properties make possible the functions
of the cell membrane, i.e., to reveal the “Membrane
Mechanisms”.
Nano Bioprocesses
Research Center for Nano Medical
Engineering
Professor : Akihiro Kusumi
Associate
Professor : Takahiro Fujiwara, Kenichi Suzuki
TEL
: +81-75-751-4112
FAX
: +81-75-751-4113
e-mail
: [email protected]
URL
: http://www.nanobio.frontier.kyoto-u.
ac.jp
Kyoto University
❶ Figure 1. Left. Single-molecule
tracking. A fluorescent or colloidal
gold tag is attached to a membrane
protein or a lipid molecule by way of
a specific antibody’s Fab fragment or
a ligand, and their movement in the
cell membrane is visualized. Right.
Using an optical trap (laser tweezers),
a membrane molecule tagged by a
gold particle is moved at will along the
cell membrane, by moving the laser
tweezers that trap the gold particle.
The force exer ted on this single
molecule from the membrane skeleton
or microdomains is registered at every
pixel.
❷ Figure 2. Inactive signaling protein
Ras, located on the cytoplasmic
surface of the plasma membrane
(green), undergoes regulated Brownian
diffusion (yellow trajectories). By the
method we developed, the activation of
this single Ras molecule was imaged
(green color changes to red, due to
FRET, at the center of this image),
which entails the first successful
observation of the activation of a single
molecule. Many other cytoplasmic
molecules are recruited to this activated
Ras molecule, inducing immobilization
of this activated Ras signaling complex.
S u r p r i s i n g l y, s u c h a m o l e c u l a r
complex disintegrates within a second,
suggesting a possibility that the basic
unit of the cellular signal occurs like a
digital pulse. Such observations are
only possible with single-molecule
imaging, rather than observing the
average behavior of many molecules.
❸ F i g u r e 3 . A d i s c o v e r y, w h i c h
necessitated a paradigm shift of the
concept of the plasma membrane
str ucture and function, has been
made. The entire plasma membrane
is par titioned into many small
compartments of 30 – 200 nm
(depending on the cell type) due to the
actin-based membrane skeleton (fence,
left) and var ious transmembrane
proteins anchored to the membrane
skeleton (pickets, right).
Recent Publications
1. N. Morone et al. Three-dimensional reconstruction of the membrane skeleton at the plasma
membrane interface by electron tomography. J. Cell Biol. 174, 851-62 (2006).
2. K. G. N. Suzuki et al. GPI-anchored receptor clusters transiently recruit Lyn and Gα for temporary
cluster immobilization and Lyn activation: single-molecule tracking study 1. J. Cell Biol. 177, 717730 (2007).
3. K. G. N. Suzuki et al. Dynamic recruitment of phospholipase Cγ at transiently immobilized GPIanchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2. J. Cell
Biol. 177, 731-742 (2007).
4. K. A. K. Tanaka et al. Membrane molecules mobile even after chemical fixation. Nature Methods
7, 865-866 (2010).
5. R. S. Kasai et al. Full characterization of GPCR monomer-dimer dynamic equilibrium by single
molecule imaging. J. Cell Biol. 192, 463-480 (2011).
Research Center for Nano Medical Engineering
Not only gravity, but many kinds of dynamic environment are influential in the function of living bodies. The dynamic
environment is mainly essential for the human body, but occasionally it may become a danger of impairments. However, the total
mechanism has not been clarified yet. In our department, all members are striving to develop computer simulation methods and
models in order to clarify the mechanical behavior and function of the living tissues from nano-level in the cell to whole body
under such dynamic environment.
We welcome the participation of students who have creative curiosity and enthusiasm to research objects in coordination area
among medicine, engineering and pharmaceutical sciences.
We are doing both basic and applied research projects
to assist the diagnosis/treatment for the functional
regenerative medicine of the living body by means
of computer science and biomaterial engineering in
development of artificial organs which harmonize
biomechanically with the living tissues. It is
indispensable in the regenerative medicine for
differentiation and proliferation of stem cells to
useful cells/tissues/organs to develop the technology
of the nano medical engineering such as proper
stimulation control of the cell environment, and
acquisition and analysis of answer signals of the
cells.
It is important to assure the biomechanical
compatibility between artificial organs and the
periphery living tissues. If the biomechanical
compatibility is not good, re-operation becomes
needed due to adaptational transformation such
as contraction/absorption of the living issues.
Accordingly, it is necessary to know the mechanical
characteristics of the living tissues first of all,
however, it has been difficult to measure in situ
condition by the conventional engineering method,
although. Thereupon, we are tackling with the
development of the original methods that measures
the dynamic characteristics and functions of
the living body invasively. On the basis of the
information that was obtained by our novel methods
with sound wave and MRI etc, computer simulations
are utilized to examine and predict what influences
of external forces on the living body under dynamic
environment.
Furthermore, for the regeneration of the living
tissue functions, we are developing many kinds of
implants with high safe functions made of polymeric,
ceramic and metallic materials. Combinations of
artificial materials and living tissues enables design/
manufacturing of implants variously in shapes and
functions. In our department, for instance, a hybrid
type dental implants with regeneration of periodontal
ligaments has been developed, and also, various
biodegradable materials, which should be resorbed
after their mission in the living body, have been
produced.
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Research Center for Nano Medical
Engineering
Associate
Professor : Suong-Hyu Hyon
TEL
: +81-75-751-4125
FAX
: +81-75-751-4125
URL
bf04/index.html
Recent Publications
❹
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❷
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❸
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❻
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❺
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❶ Effective cryopreservation of human iPS cell
❷ New cryoprotectant (no frozenpolyamino
acid)
❸ New medical adhesive of two liquid reactive
type that has biodegradability
❹ MRI device for research of MFS (1.5T)
❺ Rat MR imaging data
❻ Result of analysis of fMRI
1. Matsumura, K., Bae ,J-Y., Hyon, S-H. : Polyampholytes as cryoprotective agents for mammalian
cell cryopreservation.Cell Transplant. Vol.19 691-699 (2010)
2. Nakai R, Azuma T, Kishimoto T, Hirata T, Takizawa O, Hyon SH, Tsutsumi S:Development of
a high-precision image-processing automatic measurement system for MRI visceral fat images
acquired using a binomial RF-excitation pulse. Magnetic Resonance Imaging.28(4):520-6 (2010)
3. Kazuaki Matsumura, _Suong-Hyu Hyon_. : Polyampholytes as low toxic efficient cryoprotective
agents with antifreeze protein properties.Biomaterials 30.4842-4849 (2009)
4. Azuma T, Nakai R, Takizawa O, Tsutsumi S: In vivo structural analysis of articular cartilage using
diffusion tensor MRI. Magnetic Resonance Imaging.27(9):1242-1248 (2009)
- Institute for Virus Research
Gene Analysis
The research projects carried out in this laboratory are concerned with post-translational events in the expression of genetic
information. Specifically, processes of protein translocation across and integration into the membrane, membrane protein
proteolysis and extracytoplasmic stress responses are investigated by combined molecular genetic, biochemical and structural
approaches.
Second group is studying the lifecycle of human papillomavirus (HPV) and the molecular mechanism of the virus-induced tumor
formation. The interaction between HIV and host immune cells is also under investigation.
Third group is studying the regulatory mechanism of Wnt/beta-catenin pathway and its role on cell biology.
Yoshinori Akiyama, D. Sci
Professor
Study of protein translocation machinery:
Translocation of newly synthesized non-cytoplasmic
proteins across the membrane is mediated by the
evolutionary conserved SecYEG complex and the
motor protein SecA in E. coli. We are studying the
dynamic interactions and structural changes of these
Sec proteins to elucidate the molecular mechanism of
the protein translocation.
❶
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Proteolysis plays important roles not only in quality
control but also in functional regulation of membrane
proteins. We are interested in both of these aspects.
Also we address the problem of how an E coli cell
responds to the “membrane stresses” caused by
accumulation of potentially deleterious abnormal
membrane proteins.
HPV infection and the tumorigenesis: HPV is an
etiological agent for benign tumors at epithelial
organ, such as warts and condylomas. The infection
of HPV has been recognized as a major risk factor
for cervical cancer. The viral life-cycle is strictly
governed by the differentiation program of the host
cell, and the cross-talk between the virus and the host
cell is an unique feature of HPV biology.
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❹
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❶ Translocation/integration, folding, and degradation of the E. coli cell surface proteins and
Regulatory mechanism of Wnt/beta-catenin
cellular responses to membrane stresses.
pathway: Wnt signaling is an essential component ❷ Crystal structure of T. Thermophilus SecA protein
of development process and carcinogenesis. We ❸ Ras activation conferred invasion potential to keratinocytes expressing high-risk type E7.
identified casein kinase Ialpha as a priming kinase ❹ Disruption of Casein kinase Ialpha (CKIalpha) by RNAi induces a naked cuticle in the
Drosophila embryo.
for the phosphorylation of beta-catenin/Arm, which
was critical for the regulation of beta-catenin/
Arm degradation. We are further investigating the
regulatory mechanisms of the signaling pathway
and trying to establish the integration in a variety of
biological aspects.
Recent Publications
Gene Analysis
Professor : Yoshinori Akiyama
Associate
Professor : Hiroyuki Sakai, Hiroyuki Mori
Assistant
Professor : Shin-ichi Yanagawa, Shin-ichiro Narita
TEL
: +81-75-751-4040
FAX
: +81-75-771-5699
e-mail
: [email protected]
URL
: http://www.virus.kyoto-u.ac.jp/Lab/
akiyama/index.html
Kyoto University
1. Akiyama, Y. (2009) Quality control of cytoplasmic membrane proteins in Escherichia coli. J.
Biochem. 46, 449-54
2. Tsukazaki, T.,* Mori, H.,* Fukai, S., Ishitani, R., Mori, T., Dohmae, N., Perederina, A., Sugita, Y.,
Vassylyev, D. G., Ito, K. and Nureki O. (2008) Conformational transition of Sec machinery inferred
from bacterial SecYE structures. Nature 455, 988-991. * These authors contributed equally to this
work.
3. Koide, K., Ito. K., and Akiyama, Y. (2008) Substrate recognition and binding by RseP, an
Escherichia coli intramembrane protease. J. Biol. Chem. 283, 9562-9570.
4. Yoshida, H., Kajitani, N., Satsuka, A., Nakamura, H. and Sakai, H. (2008) Ras modifies
proliferation and invasiveness of cells expressing human papillomavirus oncoproteins. J. Virol. 81,
8820-8827
5. Matsubayashi, H., Sese, S., Lee, J.S., Shirakawa, T., Iwatsubo, T., Tomita, T. and Yanagawa, S.
(2004) Biochemical characterization of the Drosophila wingless signaling pathway based on RNA
interference. Mol Cell Biol. 24, 2012-2024
Cell Regulation
Viral Oncology
The universe of antigens recognized by the immune system has recently been expanded to include not only protein antigens
but also lipid antigens. The Lipid-specific T cell response is mediated primarily by a novel lineage of antigen-presenting
molecules, CD1, that exhibits an outstanding ability to bind lipid antigens and present them to specific T cells. By orchestrating
immunological, cell biological, and biochemical approaches, our laboratory aims to establish the molecular and cellular basis
for lipid antigen presentation and T cell activation, hoping to contribute to accurate diagnosis of cancer and microbial infection
and develop a new type of lipid-based vaccines. We encourage young investigators interested in our research endeavors to join
us regardless of their educational backgrounds.
Masahiko Sugita, M.D., Ph.D.
Professor
Rapid progress in molecular biology in the 1980s
resulted in elucidation of a molecular basis for
the protein antigen-specific immunity. Milestone
discoveries such as X-ray crystallographic
visualization of peptide-MHC interactions and
the diversity of T-cell receptors generated by gene
rearrangement convinced most immunologists
with excitement that the molecular basis for
“antigen specificity”, a most salient feature of our
immune system, had been fully disclosed. While
sharing excitement as one among members of the
immunology community, I was personally puzzled
by a naive question that came up to me after clinical
practice. “Does the universe of antigens recognized
by the immune system only include proteins?”
Glycan-specific immune responses are elicited
following pneumococcal infection. Campylobacter
infection often induces immune responses directed
against glycolipids. Autoantibodies against doublestrand DNA are detected in patients with systemic
lupus erythematosus. These clinical observations
provide evidence for the yet unappreciated ability
of the immune system to specifically recognize
non-protein antigens that include sugars, lipids,
and nucleic acids. Our laboratory now aims to
unravel a molecular and cellular basis for the lipidspecific immune response and to develop lipid-based
vaccines against cancer and microbial infection.
Young investigators sharing enthusiasm with us
would join in our journey to these goals.
Cell Regulation
Professor : Masahiko Sugita
Associate
Professor : Isamu Matsunaga
TEL
: +81-75-751-4028
FAX
: +81-75-752-3232
e-mail
: [email protected]
URL
SugitaLab.html
❶ In contrast to MHC molecules
that present protein antigens
to T cells, CD1 molecules bind
lipid antigens and present them
to T cells. These two pathways
function cooperatively to support
host defense.
❷ Electron micrographs of
dendritic cells (left) that primarily
function to mediate lipid antigen
presentation and dendritic
cell lysosomes (right) where
lipid antigen loading onto CD1
molecules occurs.
❸ Guinea pigs used for our study
of CD1 (upper panel) and CD1positive cells in CD1 transgenic
mice (lower panel, stained in
brown).
❹ A group photo of our laboratory
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Recent Publications
1. Nakao, H., et al. (2009) Mycolyltransferase from Mycobacterium leprae excludes mycolatecontaining glycolipid substrates. J. Biochem. 146:659-665.
2. Otsuka, A., et al. (2008) Trehalose dimycolate elicits eosinophilic skin hypersensitivity in
mycobacteria-infected guinea pigs. J. Immunol. 181:8528-8533.
3. Matsunaga, I., et al. (2008) Mycoyltransferase-mediated glycolipid exchange in Mycobacteria. J.
Biol. Chem. 283: 28835-28841.
4. Matsumoto, Y., et al. (2008) Guillain-Barre syndrome-associated IgG responses to gangliosides are
generated independently of CD1 function in mce. J. Immunol. 181: 39-43.
5. Hava, DL., et al. (2008) Evasion of peptide, but not lipid antigen presentation, through pathogeninduced dendritic cell maturation. Proc. Natl. Acad. Sci. USA. 105: 11281-11286.
Human Tumor Viruses
Department of Viral Oncology
Life is characterized by the interaction of individuals with their surroundings, including pathogens such as viruses. Upon
infection, viruses interfere with normal cellular function to create an environment amenable to viral replication and the
production of infectious particles, but hosts have evolved mechanisms to inhibit the spread of infection. Clarification of
the molecular mechanisms of anti-viral pathways will facilitate our understanding of host resistance as well as inform our
knowledge of normal cellular physiology. Additionally, viral infection is known to give rise to multiple pathological states
including cancer, and increased knowledge of anti-viral defense could lead to prevention of viral related diseases. We welcome
candidates who are enthusiastic to investigate this growing and important field.
Keizo Tomonaga, D.V.M., Ph.D
Professor
Depending on the particular virus, infections can be
subclinical or lead to systemic syndromes including
cancer or death. There are at least six viruses known
to cause cancer in humans, and they are referred to
as oncogenic viruses. Using human T-cell leukemia
virus and hepatitis C virus, we are investigating
the mechanisms of viral replication in the hopes of
developing useful anti-viral agents. Additionally,
we wish to clarify the molecular mechanisms by
which these viruses regulate cell proliferation.
Some proteins of oncogenic viruses modulate cell
proliferation, and an increased understanding of
the mechanism of action of viral proteins could
provide valuable insight into the normal physiology
of cell proliferation. Through comparisons of cell
proliferation in infected and uninfected cells, a
comprehensive analysis of the characteristics of cell
proliferation in these two states can be undertaken.
❶ Borna disease virus
persistently infected
neuronal cells. Left and
right panels show DIC
and confocal microscope
i m a g e s , r e s p e c t i ve l y.
The vir us-specific dot
str uctures (green) are
formed in the cell nucleus
(blue).
❷ Reduction of Purkinje cell
neurons in the cerebellum
of transgenic mice
expressing Borna disease
virus phosphoprotein in
astrocytes.
❸ Electron microscopic
obser vation of human
T-cell leukemia virus.
❹ A putative image of HCV
replication complex.
HCV alters structure of
ER membrane so that
the virus establishes the
replication complex shown
here.
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Recent Publications
Human Tumor Viruses
Professor : Keizo Tomonaga
Associate
Professor : Makoto Hijikata
TEL
: +81-75-751-4046
FAX
: +81-75-751-3998
e-mail
: [email protected]
URL
hitogan2007/index.html
Kyoto University
1. Honda T, Fujino K, Okuzaki D, Ohtaki N, Matsumoto Y, Horie M, Daito T, Itoh M and Tomonaga
K. Upregulation of insulin-like growth factor binding protein 3 in astrocytes of transgenic mice
expressing Borna disease virus phosphoprotein. J. Virol. (in press)
2. Horie M, Honda T, Suzuki Y, Kobayashi Y, Daito T, Oshida T, Ikuta K, Jern P, Gojobori T, Coffin
JM and Tomonaga K. Endogenous non-retroviral RNA virus elements in mammalian genomes.
Nature 463:84-87 (2010)
3. Watanabe Y, Ohtaki N, Hayashi Y, Ikuta K and Tomonaga K. Autogenous translational regulation
of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA
helicases. PLoS Pathog. 5:e1000654 (2009)
4. Aly HH, Qi Y, Atsuzawa K, Usuda N, Takada Y, Mizogami M Shimotohno K, Hijikata M. Straindependent viral dynamics and virus cell interactions observed in a novel in vitro system supporting
the life cycle of blood borne HCV. Hepatology 50:689-696. (2009)
5. Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, Zayas M, Bartenschlager R, Wakita
T, Hijikata M, Shimotohno K. The lipid droplet is an important organelle for hepatitis C virus
production. Nat. Cell Biol. 9:1089-1097. (2007)
Biological Protection
Department of Biological Responses
The immune system has acquired sophisticated control mechanisms as a result of evolution at the front line of the war between
host and microorganism. Thus, the immune system is important not only as a self-defense mechanism against pathogenic
microorganisms but also as an interesting research field full of unexpected findings. Our laboratory aims to find new principles
that are universal to medicine and biology. Therefore, we welcome young students with much enthusiasm and interest in
immunology.
Koichi Ikuta, M.D., Ph.D.
Professor
The immune system has adopted the strategy
“Learn oneself, and then learn the enemy” to fight
against pathogenic microorganisms. The step
“Learn oneself” is the stage of development and
differentiation of immune cells. This stage includes
important questions such as the decision of cell
destiny and the control of lymphocyte differentiation.
Our themes mainly reside in these fields, which are
full of unsolved questions.
Our laboratory has made two major achievements.
First, we have found that fetal and adult
hematopoietic stem cells have different
developmental potential to differentiate into
lymphocytes. Second, we have demonstrated that
interleukin-7 controls DNA recombination of
lymphocyte antigen receptor genes by changing
chromatin structure. Both of them are related with
fundamental questions in medicine and biology.
Based on these findings, we are now pursuing
research on development of the immune system
and regulation of immune response, focusing on the
following questions: (1) molecular mechanism of
lineage decision of immune cells from hematopoietic
stem cells; (2) control mechanism of lymphocyte
antigen receptor genes by chromatin structural
changes; (3) regulation of immune response by
controlling cytokine receptor expression; (4)
distribution and function of IL-7-producing cells.
In our laboratory, every graduate student will be
involved in one of the projects and trained as to
acquire the ability to plan, accomplish and publish
one’s work. In the process, one will acquire the
skills on flow cytometry, cell sorting, organ culture,
transgenic and knockout mice as well as general
techniques on molecular biology, cell biology, and
immunology.
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❶ gamma/deltaT cells (red) and
dendritic cells (green) in the
epithelium of wild-type mouse
skin. IL-7 receptor knockout
mice lack gamma/deltaT cells.
❷ IL-7 receptor knockout mice
lack gamma/deltaT cells in the
epithelium of small intestine.
❸ Stat5, activated by IL-7
receptor, binds to the T cell
antigen receptor gammac h a i n l o c u s, c h a n g e s i t s
chromatin structure by
histone acetylation, and
induces transcr iption and
recombination.
Recent Publications
Biological Protection
Professor : Koichi Ikuta
Assistant
Professor : Masamichi Ueda, Shizue Tani-ichi,
Takahiro Hara
TEL
: +81-75-751-4012
FAX
: +81-75-751-4810
e-mail
: [email protected]
URL
ikuta.html
1. Ye SK, Maki K, Kitamura T, Sunaga S, Akashi K, Domen J, Weissman IL, Honjo T, Ikuta K (1999):
Induction of germline transcription in the gamma locus by Stat5: implications for accessibility
control by the IL-7 receptor. Immunity, 11:213-223.
2. Ye SK, Agata Y, Lee HC, Kurooka H, Kitamura T, Shimizu A, Honjo T, Ikuta K (2001): The
IL-7 receptor controls the accessibility of the TCRgamma locus by Stat5 and histone acetylation.
Immunity, 15:813-823.
3. Lee HC, Ye SK, Honjo T, Ikuta K (2001): Induction of germline transcription in the human T cell
receptor gamma locus by STAT5. J. Immunol., 167:320-326.
4. Lee HC, Shibata H, Ogawa S, Maki K, Ikuta K. (2005): Transcriptional regulation of the mouse
IL-7 receptor alpha promoter by glucocorticoid receptor. J. Immunol., 174:7800-7806.
5. Maki, K., Ikuta, K. (2008): MEK1/2 induces STAT5-mediated germline transcription of the
TCRgamma locus in response to IL-7R signaling. J. Immunol., 181:494-502.
Infection and Prevention
Biological Responses
We investigate the molecular mechanism of thioredoxin binding protein-2 (TBP-2)/ Txnip and alpha-arrestin proteins which
attract much attention as multifunctional regulators in the pathogenesis of diseases including cancer and Diabetes Mellitus.
We perform multidimensional approaches such as analyses of knockout mice and multiomics, in tight collaborations with
researchers in clinical departments. Our goal is to elucidate the pathogenesis of these diseases and develop approaches against
these diseases.
We investigate the molecular mechanism of
thioredoxin binding protein-2 (TBP-2/Txnip) and
alpha-arrestin family proteins, to elucidate the
pathogenesis of and to develop approaches against
Diabetes Mellitus, cancer, and viral infection.
Main research projects are
1. Study of the mechanism TBP-2/ Txnip for
Diabetes Mellitus, cancer, and viral infection. We
showed that TBP-2 is an important molecule in the
pathogenesis of Diabetes Mellitus. TBP-2 regulates
the secretion of insulin, sensitivity of insulin and
apoptosis. We also revealed that TBP-2 regulates the
transcription of important metabolic regulatory genes
through the control of co-activators. We are now
investigating the molecular mechanism of TBP-2 in
order to develop new approaches against Diabetes
Mellitus.
TBP-2 also plays important roles in cancer
suppression and the regulation of inflammatory
response. We are studying the molecular mechanism.
2. Study of TLIMP/ ARRDC3, an alpha-arrestin
protein in the regulation of receptor endocytosis.
TBP-2-like inducible membrane protein (TLIMP)/
arrestin domain containing protein 3 (ARRDC3)
regulates the endocytosis of receptors such as the
beta2-adrenagic receptor. Since TLIMP/ ARRDC3
may act as an adaptor/ scaffold to regulate
endocytotic process and signals of various receptors,
we are studying the molecular function of TLIMP/
ARRDC3.
3. Study of redox and oxidative stress signaling.
We are investigating redox and oxidative stress
signaling by analyzing molecular functions of
thioredoxin family proteins.
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❶ Multiple Biological Roles of
Thioredoxin Binding Protein-2 (TBP2)/ Txnip and alpha-Arrestin Family
Proteins. TBP-2/Txnip is involved in
various diseases such as Diabetes
Mellitus, hyperlipidemia, Cancer and
inflammatory disorders.
❷ Improvement of hyperglycemia by
disruption of TBP-2 in ob/ob mice,
a genetic animal model of human
obesity and type 2 Diabetes Mellitus.
Disruption of TBP-2 did not change
obesity (left, and right upper figure)
but improved hyperglycemia (right
lower).
❸ Regulation of receptor endocytosis
by TBP-2-like Inducible Membrane
Protein (TLIMP)/ Arrestin Domain
Containing 3 protein (ARRDC3).
TLIMP/ ARRDC3 regulates
endocytosis, ubiquitination,
degradation, and signal transduction
of receptors. TLIMP/ ARRDC3
is located in inner membrane,
endosomes and lysosomes (left
lower).
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We use multidimensional approaches, connecting
structural analyses, proteome and transcriptome
analyses, biochemical and physiological approaches
and analyses in pathophysiology, in a tight
collaboration with clinical departments. We educate
graduate students based on their own motivations
and interests. Graduate students with various
backgrounds gather in our laboratory. We welcome Recent Publications
the visit of young investigators.
1. Yoshihara, E., Fujimoto, S., Inagaki, N., Okawa, K., Masaki, S., Yodoi, J., Masutani, H. (2010)
Infection and Prevention
Associate
Professor : Hiroshi Masutani
TEL
: +81-75-751-4026, 4025
FAX
: +81-75-761-5766
e-mail
: [email protected]
URL
: http://www.virus.kyoto-u.ac.jp/virus/
kanbou.html
Kyoto University
Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity. Nat
Commun., 1:127.
2. Chen, Z., Lopez-Ramos, DA., Yoshihara, E., Maeda, Y., Masutani, H., Sugie, K., Maeda,
M., Yodoi, J. (2010) Thioredoxin-binding protein-2 (TBP-2/VDUP1/TXNIP) regulates T-cell
sensitivity to glucocorticoid during HTLV-I-induced transformation. Leukemia.
3. Mochizuki, M., Kwon, YW., Yodoi, J., Masutani H. (2009) Thioredoxin regulates cell cycle via the
ERK1/2-cyclin D1 pathway. Antioxid Redox Signal. 11, 2957-2971.
4. *Oka, S., *Yoshihara, E., Bizen-Abe, A., Liu, W., Watanabe, M., Yodoi, J., Masutani, H. (2009)
Thioredoxin binding protein-2/thioredoxin-interacting protein is a critical regulator of insulin
secretion and peroxisome proliferator-activated receptor function. Endocrinology. 150, 1225-1234.
* These authors contributed equally to this work.
Growth Regulation
Department of Cell Biology
It is really fascinating and exciting to see the process where a fertilized egg develops into a complicated embryo. How does
each cell in embryos know its own position and role? How do many events proceed coordinately at the right time and the right
place? Many things remain to be solved in developmental biology. We are challenging these difficult but fascinating problems of
developmental biology. The results from this research will be useful for the future regeneration therapy. We hope many students
will join us to challenge these problems.
Ryoichiro Kageyama, M.D., Ph.D.
Professor
The research interest of this laboratory is to
understand the molecular mechanism of cell
differentiation and organogenesis. Particularly, we
are interested in transcription factors that regulate
neural development. Our research strategies are
misexpressing the genes with retrovirus and
electroporation (gain-of-function study) and
generating knock-out mice (loss-of-function study).
We are focusing on basic helix-loop-helix (bHLH)
transcription factors such as the repressor-type
bHLH factors Hes1 and Hes5 and the activatortype bHLH factors Math, Mash, NeuroD and
Neurogenin. During neural development, the
following three major steps occur sequentially: (1)
maintenance of neural stem cells, (2) neurogenesis
and (3) gliogenesis. We have demonstrated that the
steps (1) and (3) are regulated by the repressor-type
bHLH factors while the step (2) is regulated by the
activator-type bHLH factors. These findings will be
useful for the future regeneration therapy.
We are also interested in biological clocks that
regulate embryogenesis. We have recently found that
the bHLH factors Hes1 and Hes7 act as two-hour
cycle biological clocks in embryos. Hes7 regulates
the timing of somite segmentation, which occurs
every two hours in mice. We are now studying
what developmental processes, besides somite
segmentation, these biological clocks regulate. This
research will open the new field “Developmental
Chronobiology”.
Regarding education, we are committed to providing
graduate students with the highest quality of research
environment and thereby educating them to be the
scientists who play an essential role in international
societies. Students with various backgrounds study
Developmental Biology from the beginning and join
the research project described above. They have the
opportunity to present and discuss their results in
domestic and international meetings and to publish
them in international journals.
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❶ bHLH factors regulate three
steps of neural development.
❷ The repressor-type bHLH
factors Hes1 and Hes5 are
e s s e n t i a l fo r m a i n t e n a n c e
of neural stem cells. (Upper)
In the absence of Hes1 and
Hes5, neurons are prematurely
differentiated and neural stem
cells are not maintained.
(Lower) Hes1;Hes5 doublenull neural stem cells do not
grow well and form only small
neurospheres.
❸ Hes1 and Hes7 as two-hour
cycle biological clocks. Hes1
and Hes7 expression oscillates
autonomously by negative
feedback. These biological
clocks regulate the progress of
embryogenesis.
❹ staffs
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Recent Publications
Growth Regulation
Professor : Ryoichiro Kageyama
Associate
Professor : Toshiyuki Ohtsuka
Assistant
Professor : Taeko Kobayashi
TEL
: +81-75-751-4011
FAX
: +81-75-751-4807
e-mail
: [email protected]
URL
toppage.zoushoku.kageyama.html
1. Kobayashi, T., Mizuno, H., Imayoshi, I., Furusawa, C., Shirahige, K., and Kageyama, R. (2009)
The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.
Genes & Dev. 23, 1870-1875.
2. Kageyama, R., Ohtsuka, T., Shimojo, H., and Imayoshi, I. (2008) Dynamic Notch signaling in
neural progenitor cells and a revised view of lateral inhibition. Nature Neurosci. 11, 1247-1251.
3. Imayoshi, I., Sakamoto, M., Ohtsuka, T., Takao, K., Miyakawa, T., Yamaguchi, M., Mori, K.,
Ikeda, T., Itohara, S., and Kageyama, R. (2008) Roles of continuous neurogenesis in the structural
and functional integrity of the adult forebrain. Nature Neurosci. 11, 1153-1161.
4. Shimojo, H., Ohtsuka, T., and Kageyama, R. (2008) Oscillations in Notch signaling regulate
maintenance of neural progenitors. Neuron 58, 52-64.
5. Niwa, Y., Masamizu, Y., Liu, T., Nakayama, R., Deng, C.-X., and Kageyama, R. (2007) The
initiation and propagation of Hes7 oscillation are cooperatively regulated by Fgf and Notch
signaling in the somite segmentation clock. Dev. Cell 13, 298-304.
Viral Pathogenesis
Center for Human Retroviruses Research
Human immunodeficiency virus (HIV) is a causative agent for acquired immunodeficiency syndrome (AIDS). After the
discovery of HIV, it has been well known that ‘‘retroviruses can cause some human diseases’’. We now know the importance of
retrovirus research. The isolation of human retroviruses was the 5th major discovery and provided paradigm shift on history of
Retrovirology. The 1st~4th major discoveries are as follows; (1) the isolation of a pathogenic retrovirus, (2) the development
of the focus assay for oncogenic retrovirus, (3) the discovery of reverse transcriptase, (4) the derivation of retroviral oncogene
from cellular genomes. It is clear that these discoveries provided strong advances not only on Virology itself but also general Cell
Biology. Information on Molecular Biology has been obtained from these retrovirus researches. Therefore, we believe that our
efforts will contribute to Medical as well as Life Sciences.
Yoshio Koyanagi, M.D., Ph.D.
Professor
Research projects have been arranged for graduate
students and they should join in international
scientific fields.
1) Replication of viral genome
Virus infects cell and replicates. Viral genome moves
from virion-produced cell to adjacent naive cells.
This is a most significant characteristics of virus.
The mechanism of this infection event is a primary
theme. The genome movement is not restricted in cell
to cell infection. Inside cells, viral genomes or/and
viral proteins move. Virus uses cellular trafficking
machinery. We wish to learn the mechanism. (Fig. 1.
Entry steps of HIV)
2) Regulation of HIV replication by immunological
molecules
Virus cannot replicate without cells. However, we
don’t know yet how many cellular factors virus
requires for its replication. Since it has been finding
many factors on HIV replication, we wish to learn
the mechanism of HIV replication from aspect of
Immunology and Virology.
3) Mechanism of HIV pathogenesis
HIV causes immunodeficiency in human.
The mechanism of the immunodeficiency
remains unclear. It has been analyzing how the
immunodeficiency occurs using in vitro-cell culture
models and in vivo-animal models. We developed
a mouse system that human immune system is
transplanted in SCID mouse and in this humanchimera mouse abundant CD4 cell killing can be
reproduced with HIV infection.
4) Development of retrovirus vector system for gene
therapy and gene discovery
Virus transmits the gene into cells. It has been trying
to take advantage of this viral nature for gene therapy
in human disease. HIV-based retrovirus vector has
promising properties to infect non-dividing cell
and integrate in chromosome DNA. Purpose of this
project is improvement of the vector system for
practical use as well as discovery of gene functions.
Viral Pathogenesis
Professor : Yoshio Koyanagi
Assistant
Professor : Hirotaka Ebina
TEL
: +81-75-751-4813
FAX
: +81-75-751-4812
e-mail
: [email protected]
URL
koyanagi-lab-home.htm
Kyoto University
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❶ Entry step of HIV.
❷ Humanized SCID mouse is susceptible
for HIV infection.
❸ cDNA library-expressing lentivirus can
be used to select genes that provide the
resistance to HIV infection.
❹ Staffs
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Recent Publications
1. Sato K, Aoki J, Misawa N, Daikoku E, Sano K, Koyanagi Y. (2008) Modulation of human
immunodeficiency virus type 1 infectivity through incorporation of tetraspanin Proteins. J. Virol.
82:1021-1033.
2. Kitayama H, Miura Y, Ando Y, Hoshino S, Ishizaka Y, Koyanagi Y. (2008) Human
immunodeficiency virus type 1 Vpr inhibits axonal outgrowth through induction of mitochondrial
dysfunction J. Virol. 82:2528-2542.
3. Yoshida T, Kawano Y, Sato K, Ando Y, Aoki J, Miura Y, Komano J, Tanaka Y, Koyanagi Y. (2008)
A CD63 mutant inhibits T-cell tropic HIV-1 entry by disrupting CXCR4 trafficking to the plasma
membrane. Traffic 9, 540-558.
4. Sato K, Izumi T, Misawa N, Kobayashi T, Yamashita Y, Ohmichi M, Ito M, Takaori-Kondo A,
Koyanagi Y. (2010) Remarkable lethal G-to-A mutations in vif-proficient HIV-1 provirus by
individual APOBEC3 proteins in humanized mice. J. Virol. 84, 9546-9556.
5. Kobayashi T, Ode H, Yoshida T, Sato K, Gee P, Yamamoto SP, Ebina H, Strebel K, Sato, Koyanagi
Y. (2011) Identification of amino acids in the human tetherin transmembrane domain responsible
for HIV-1 Vpu interaction and susceptibility. J. Virol. 85, 932-945.
Viral Infections
Center for Human Retroviruses Research
Human T-cell leukemia virus type I (HTLV-I), and human immunodeficiency virus (HIV) are two major human retroviruses.
HTLV-I induces the clonal proliferation of infected cells by pleiotropic actions of viral proteins. After a long latent period,
HTLV-I causes adult T-cell leukemia (ATL) and inflammatory diseases in a part of carriers. On the other hand, HIV destroys
CD4 positive T-lymphocytes, and ruins the immune system of infected individuals, resulting in the onset of acquired
immunodeficiency syndrome (AIDS). In our laboratory, we pursue the molecular mechanisms of caner, virus induced diseases
through research of these human retroviruses.
Masao Matsuoka, M.D., Ph.D.
Professor
Our goal is to clarify the molecular mechanisms of
human retrovirus-associated diseases, adult T-cell
leukemia (ATL) and AIDS, and establish the new
therapeutic strategies against such diseases. In
HTLV-I, we are studying the molecular mechanism
of HTLV-I induced T-cell proliferation, inflammatory
diseases, and leukemogenesis. We also challenge to
establish the new strategy for treatment against ATL
based on our research.
We found that HTLV-I bZIP factor gene, which is
encoded by the minus strand of HTLV-I, play an
important role in its pathogenesis. We continue to
study the molecular mechanism of HBZ gene in ATL.
Highly active anti-retroviral therapy (HAART)
dramatically changes the treatment to HIV-infected
individuals, and improves their prognosis. However,
the eradication of HIV is impossible even by
HAART, and long-term administration of antiHIV drugs induces resistant viruses in vivo. In our
laboratory, we are developing the new anti-HIV
drugs, and analyzing the mechanism of resistance
against anti-HIV drugs.
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❶ Morphology of adult T-cell leukemia
cells. ATL cells with lobulated nuclei
are called as “flower cells”.
❷ HBZ induces T-cell lymphoma and the
inflammatory diseases in vivo.
❸ Regulatory T cells are increased in
HBZ transgenic mice.
❹ Six-helix bundle formation between
SC34EK (blue) and N-HR (N36; pink)
❺ Staff. Professor Matsuoka (left) and
Instructor Yasunaga (right)
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Recent Publications
Viral Infections
Professor : Masao Matsuoka
Instructor : Jun-ichiro Yasunaga
TEL
: +81-75-751-4048
FAX
: +81-75-751-4049
e-mail
: [email protected]
URL
matsuoka.html
1. Satou Y, Yasunaga J-I, Zhao T, Yoshida M, Miyazato P, Takai K, Shimizu K, Ohshima K, Green PL,
Ohkura N, Yamaguchi T, Ono M, Sakaguchi S, Matsuoka M. HTLV-1 bZIP Factor Induces T-Cell
Lymphoma and Systemic Inflammation In Vivo. PLoS Pathog, 7: e1001274, 2011.
2. Fan J, Ma G, Nosaka K, Tanabe J, Satou Y, Koito A, Wain-Hobson S, Vartanian JP, Matsuoka M.
APOBEC3G generates nonsense mutations in human T-cell leukemia virus type 1 proviral genomes
in vivo. J Virol, 84: 7278-7287, 2010.
3. Matsuoka M, Jeang KT. Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular
transformation. Nat Rev Cancer, 7: 270-280, 2007.
4. Tamaki H, Matsuoka M. Donor-derived adult T-cell leukemia after allogeneic bone marrow
transplantation. N Eng J Med 354: 1758-1759, 2006.
5. Satou Y, Yasunaga J-I, Yoshida M, Matsuoka M. The HTLV- I bZIP factor gene mRNA supports
proliferation of adult T-cell leukemia cells. Proc. Natl. Acad. Sci. USA, 103: 720-725, 2006.
Viral Pathogenicity
Experimental Research Center for Infectious Diseases
Due to the lack of definitive prophylactic and therapeutic measures, viral infectious diseases, such as highly pathogenic avian
influenza virus, hepatitis C and AIDS, are still major threats to humans. It is essential to elucidate the pathogenic mechanisms
induced by virus infections to establish more effective prophylaxis and therapy. To this end, we have been developing animal
models for AIDS and analyzing disease and pathogenic mechanisms using the models.
Tatsuhiko Igarashi, D.V.M. & Ph.D.
Professor
Our laboratory has been developing, improving
animal models for AIDS and analyzing the disease
and pathogenic mechanisms using the models. The
followings are our basic experimental techniques:
•Modification of molecularly cloned viruses
•Analysis of virus evolution through animal passage
•Measurement of viral burden and lymphocyte subset
•Assessment of humoral and cellular immune
reaction against virus
We are also involved in histochemical analyses of
virus-infected animals.
Our educational goal is to develop an integrated
view to host-parasite relationship at molecular,
cellular, and organism level, employing knowledge
and techniques of molecular biology, biochemistry,
virology, immunology, pathophysiology and
veterinary medicine. We wish to nurture “virologists”
who can handle virus and analyze biological
aspects of pathogenic viruses. While the progress
of molecular biology has enabled us to “dissect”
and analyze virus replication cycle more precisely
and safely, it has made “virologists” seemingly
less important. We think “virologists” are heavily
needed under the current circumstance where
infectious diseases keep emerging or re-emerging.
We encourage motivated young scientists to join our
research.
❶ Schematic representations
of genomic organization of
HIV-1, SIV, and SHIV and
virus particle of SHIV.
❷ CD4+ T cell profiles of
SHIV-infected animal (left,
pre-infection, right, post
infection, note the cell
population in the circle,
credit, Y. Fukazawa)
❸ Virus-infected cells (brown)
r ev e a l e d i n t h e s m a l l
intestine of SHIV-infected
animal (Credit, K. Inaba)
❹ Lab members
❶
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❷
●
❸
●
❹
●
Recent Publications
Viral Pathogenicity
Professor : Tatsuhiko Igarashi
Associate
Professor : Tomoyuki Miura
Assistant
Professor : Takeshi Kobayashi
TEL
: +81-75-751-3981
FAX
: +81-75-761-9335
e-mail
: [email protected]
URL
Igarashi/Top.html
Kyoto University
1. Igarashi, T., Iyengar, R., Byrum, R. A., Buckler-White, A., Dewar, R. L., Buckler, C. E., Lane, H.
C., Kamada, K., Adachi, A., and Martin, M. A. (2007b) Human immunodeficiency virus type 1
derivative with 7% simian immunodeficiency virus genetic content is able to establish infections in
pig-tailed macaques. J. Virol., 81, 11549-11552.
2. Shimizu, Y., Inaba, K., Kaneyasu, K., Ibuki, K., Himeno, A., Okoba, M., Goto, Y., Hayami,
M., Miura, T., and Haga, T. (2007) A genetically engineered live-attenuated simian-human
immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular
immunity in rhesus macaques. Virology, 361, 68-79.
3. Miyake, A., Ibuki, K., Enose, Y., Suzuki, H., Horiuchi, R., Motohara, M., Saito, N., Nakasone,
T., Honda, M., Watanabe, T., et al. (2006) Rapid dissemination of a pathogenic simian/human
immunodeficiency virus to systemic organs and active replication in lymphoid tissues following
intrarectal infection. J. Gen. Virol., 87, 1311-1320.
4. Igarashi, T., Brown, C. R., Endo, Y., Buckler-White, A., Plishka, R., Bischofberger, N., Hirsch,
V., and Martin, M. A. (2001) Macrophage are the principal reservoir and sustain high virus
loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian
immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans.
Proc. Natl. Acad. Sci. U. S. A., 98, 658-663.
5. Igarashi, T., Brown, C., Azadegan, A., Haigwood, N., Dimitrov, D., Martin, M. A., and Shibata R.
(1999) Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell
free virions from blood plasma. Nat. Med. 5(2): 211-216.
- Research Reactor Institute
Radiation Biology
Division of Radiation Life Science
Radiation biology has recently come to attract attention as an investigational area contributing to elucidation of various heredity
mechanism from classic study of conventional radiation influence. Especially, it is a topics that genetic effect by radiation
exposure is propagated via spatial (bystander effects) and time distance (delayed effects). We are aiming to clarify the non-DNA
target of hereditary influence by radiation and the mechanism to maintain gene homeostasis.
Masami Watanabe, Ph.D.
Professor
❶
●
After the life was born on the earth 3,600 million
years ago, the life has not been separated from
various environmental stress, such as radiation,
temperature and pressure. And the life built cell
structure to distinguish it from the surrounded
environment. Recently, it has been made clear that
a cell are using basic biological reaction mechanism
for replying to various stress. Therefore, basic
biological reaction may be clarified by discovering
stress response mechanism. Dysfunction of stress
response may be a cause of carcinogenesis and
acceleration of aging. It is also expected that a
disease is cured by fixing a stress response function
normally. We choose four environmental stress ❶ It has been believed that the first target of radiation carcinogenesis is DNA.
factors, such as radiation, hyperthermia, oxygen and
However, this hypothesis is not yet proved for carcinogenesis from low-dose radiation
directly.
pressure, and are doing the study focused on the
We analyzed our results of research on malignant cell transformation by low-dose
following topics along such a working hypothesis.
radiation during the past 30 years and came to strongly believe that a main target
(1) Mechanism of carcinogenesis and aging
of radiation carcinogenesis is not DNA, but the centrosome, which is a protein that
(2) Mechanism of stress response
constitute the chromosomal homeostasis maintenance mechanism.
(3) Development of new cancer therapy by
If our results are correct, the “mutation theory of carcinogenesis" is wrong.
We suggest a new hypothesis about radiation carcinogenesis, which we named the
hyperthermia and radiation
“protein-target
hypothesis,” or, alternatively, the “aneuploidy-cancer hypothesis.” Picture;
(4) A search of cancer and aging prevention natural
Normal centrosome (left upper) and normal nuclear division (left lower), structural
material
change of centrosome (upper and lower of center) and abnormal nuclear division (upper
Our investigational purpose is prevention and a
and lower of right).
treatment of cancer and aging.
Recent Publications
Radiation Biology
Professor : Masami Watanabe
Associate
Professor : Keizo Tano
Assistant
Professor : Genro Kashino
TEL
: +81-72-451-2391
FAX
: +81-72-451-2628
e-mail
: [email protected]
URL
: http://www.rri.kyoto-u.ac.jp/rb-rri/rbrri1e.html
1. Toyokuni H, Maruo A, Suzuki K, Watanabe M: The contribution of radiation-induced large
deletion of the genome to chromosomal instability. Radiat. Res. in press, 2008
2. Harada Tm, Kashino G., Suzuki K, Matsuda N, Kodama S, Watanabe M: Different involvement of
radical species in irradiated and bystander cells. Intern. J. Radiat. Biol, in press, 2008
3. Masunaga S, Keizo Tano K, Watanabe M, Kashino G, Suzuki M, Kinashi Y, Ono K, Nakamura
J: Evaluation of the potential of hexamethylenetetramine as a combined agent with gammaray irradiation and cisplatin treatment in vivo, compared with tirapazamine British Journal of
Radiology, in press, 2008
4. Yamauchi M, Oka Y, Yamamoto M, Niimura K, Uchida M, Kodama S, Watanabe M, Sekine I,
Yamashita S, Suzuki K: Growth of persistent foci of DNA damage checkpoint factors is essential
for amplification of G1 checkpoint signaling. DNA Repair (Amst). 7(3): 405-417, 2008.
5. Hamamoto T, Suzuki K, Yamauchi M, Kodama S, Sasaki H, Watanabe M: p53 status-dependent
sensitization of human tumour cells to hyperthermia by plant flavonol. Int J Hyperthermia. 24(5):
415-424, 2008.
- Research Reactor Institute
Particle Radiation Oncology Research Center
Kyoto University has 5 MW nuclear reactor for research at Kumatori in Osaka. A heavy water facility is attached to the reactor,
and use of thermal and epithermal neutrons is available for researches of medicine and biology. Among them, development of
boron neutron capture therapy (BNCT) for malignant tumors is most important and attractive subject. B-10 atom absorbs thermal
neutron and emits high LET alpha particle. So, if B-10 accumulates in tumors selectively, only the tumor can be destroyed. In our
country and also in the world, most patients have been treated in my reactor by our research group. Furthermore, development
research of accelerator to generate neutrons for BNCT is also advanced, and the performance of clinical trial possible is realized.
We welcome young researchers who aim both clinical and basic researches for BNCT.
at much higher probability compared with other elements like as nitrogen, with shorter track than cancer cell diameter.
Koji Ono, MD.PhD
Professor
■ Radiation and Tumor Biology Research for BNCT
The range of the particles emitted through the
reaction of B-10 nucleus and thermal neutron does
not exceed the diameter of a cancer cell. On the other
hand, the sell killing effect of thermal neutron itself is
quite small. Moreover, capture probability of neutron
with B-10 nucleus is extraordinarily large compared
with reactions with other element nucleus in human
body. Therefore, if B-10 compound accumulates
in cancer cell or cancer tissue selectively, selective
destruction and treatment of cancer cell or cancer is
achievable. For liver cancer with multiple lesions
we succeeded to accumulate B-10 compound at
very high concentration and selectivity by using the
technology of IVR. And by our original procedure,
BNCT of liver cancer was performed first in the
world. It is impossible to deliver curative radiation
dose to the malignant pleural mesothelioma (MPM)
which takes very complicated three dimensional
lesions by X-ray irradiation technology avoiding
lung tissue which adjoined intricately. Amino acid
analogue involving B-10, BPA, accumulates in MPM
pretty selectively through increased amino acid
metabolism. When the effect was examined by the
pleura dissemination model of cancer cells in rat,
large extension of the survival time was obtained
only by the BNCT group, and BNCT for MPM
patient was carried out first in the world. Thus, basic
research and clinical study are linked tightly and
directly, and research is advanced.
■ Physical and Engineering Research for BNCT
The neutron for BNCT has a fault with poor
penetration into the deep part of body.
In order to overcome this, the ideas of air injection
to a postoperative dead space and shielding of
the central part of the neutron exposure field was
devised, and they have been applied to clinical
BNCT. The performance of accelerator to generate
neutrons for BNCT first in the world has reached Recent Publications
the level in which a clinical trial is possible, and it is 1. Minoru Suzuki, KazuoEndo, Hiroaki Satoh, Yoshinori Sakurai, Hiroaki Kumada, Hiroyuki
Kimura, Shinichiro Masunaga, Yuko Kinashi, Kenji Nagata, Akira Maruhashi, Koji Ono, "A
noted that neutron distribution of the accelerator is
novel concept of treatment of diffuse or multiple pleural tumors by boron neutron capture therapy
superior to a reactor neutron.
Professor : Koji Ono
Associate
Professor : Shin-ichiro Masunaga
Assistant
Professor : Yong Liu·Natsuko Kondo
TEL
: 072-451-2575
FAX
: 072-451-2627
e-mail
: [email protected]
Kyoto University
(BNCT)", Radiotherapy and Oncology 88 (2008) 192-19
2. M. Suzuki, H. Tanaka, Y. Sakurai, G. Kashino,Y. Liu, S. Masunaga, Y. Kinashi, T. Mitsumoto, S.
Yajima, H. Tsutsui, T. Sato, A. Maruhashi, K. Ono, “Impact of accelerator-based boron neutron
capture therapy (AB-BNCT) on the treatment of multiple liver tumors and malignant pleural
mesothelioma”, Radiotherapy and Oncology 92(2009)89-95
3. H.Tanaka, Y.Sakurai, M.Suzuki, S.Masunaga, Y.Kinashi, G.Kashino, Y.Liu, T.Mitsumoto,
S.Yajima, H.Tsutsui, A.Maruhashi, K.Ono, "Characteristics comparison between a cyclotron-based
neutron source and KUR-HWNIF for boron neutron capture therapy",Nuclear Instruments and
Methods in Physics Research B 267 (2009) 1970–1977
4. G.ASHINO, S. FUKUTANI, M. SUZUKI, Y. LIU, K. NAGATA, S. MASUNAGA, A.
MARUHASHI, H. TANAKA, Y. SAKURAI, Y. KINASHI, N. FUJII and K. ONO, “A Simple and
Rapid Method for Measurement of10B-para-Boronophenylalanine in the Blood forBoron Neutron
Capture Therapy UsingFluorescence Spectrophotometry” Journal of Radiation Research 50 (2009)
377-382
- Center for Southeast Asian Studies
Division of Integrated Area Studies
Infection is the war between the pathogen and its host. It is important to understand the nature of the both sides to prevent
and treat the infection. Pathogenic bacteriology is the study on the bacterial pathogen and it is not very simple. The habitat of
most bacterial pathogens is not humans but the natural environment. Knowledge and techniques of various fields are needed
to understand how the pathogenic bacteria distinguish the natural environment and humans and how they act in the different
environments. Some infections are spread across the international borders and international collaboration among the researchers
is imperative to study the epidemiology.
Mitsuaki Nishibuchi, Ph.D.
Professor
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❹
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We carry out comprehensive studies on the enteric
infections caused by the pathogens such as Vibrio
cholerae, Vibrio parahaemolyticus, and diarrheagenic
Escherichia coli in our department. These infections
are important, in particular, in Southeast Asia and
isolation of the pathogens from the environment and
the patients in collaboration with the workers in this
area is the first step of the study. We not only identify
the isolated bacterium but also, if needed, distinguish
whether the isolates are pathogenic or nonpathogenic
❷
strains and examine for special characteristics (the ●
serotype, phage type, genotype, etc.)
We analyze the isolated strains not only for
phenotypic characteristics but for their DNA
fingerprints to investigate whether a particular strain
in the environment is responsible for the infection
or the infection is spread across the international
borders.
It is also important to study how the pathogenic
❸
●
strains distinguish the signals in the natural
environment and the host and then express their
virulence properties. To study this, we first identify
the major virulence factor and the gene encoding this
factor and then detect related genes and elucidate the
mechanism regulating their expressions. We propose
a working hypothesis from the results. The strains
collected as above are very important property to
examine the universality of the working hypothesis.
We carry out the experiments and samplings by using
the techniques associated with the environmental ❶ The research team in Malaysia that collaborated in isolation of Escherichia coli O157
microbiology, clinical microbiology, molecular ❷ We revealed that the Kanagawa phenomenon to detect pathogenic strains of Vibrio
parahaemolyticus (left) is not observed if a specific one-base change occurs in the tdh
genetics, physiology, and immunology.
promoter.
❸ The DNA fingerprinting analysis that led to the discovery of the first pandemic spread of
Vibrio parahaemolyticus infection. The newly emerged pandemic strains in the left panel
showed a fingerprint that differed from those of the other strains.
Recent Publications
Professor : Mitsuaki Nishibuchi
TEL
: +81-75-753-4442
FAX
: +81-75-753-7350
e-mail
: [email protected]
URL
: http://www.cseas.kyoto-u.ac.jp/
1. Nakaguchi, Y., and M. Nishibuchi. 2005. The promoter region rather than its downstream inverted
repeat sequence is responsible for low-level transcription of the thermostable direct hemolysinrelated hemolysin (trh) gene of Vibrio parahaemolyticus. J. Bacteriol. 187(5):1849-1855.
2. Koitabashi, T., V. Vuddhakul, S. Radu, T. Morigaki, N. Asai, Y. Nakaguchi, and M. Nishibuchi.
2006. Genetic characterization of Escherichia coli O157:H7/- strains carrying the stx2 gene but not
producing Shiga toxin 2. Microbiol. Immunol. 50(2): 135-148.
3. Koitabashi, T., S. Cui, K. Muhammad, and M. Nishibuchi. 2008. Isolation and characterization
of the Shiga toxin gene (stx)-bearing Escherichia coli O157 and non-O157 from retail meats in
Shandong Province, China and characterization of the O157-derived stx2 phages. J. Food Prot.
71(4):706-713.
- Center for Southeast Asian Studies
Field Medicine
Division of Humans and the Environment
Modern clinical (bed-side) medicine have much succeeded in the lifesaving of the patients with acute diseases. As the results
now, aging population have developed not only developed countries but also developing countries. However, modern clinical
medicine in the hospital cannot completely deal with community-dwelling frail elderly patients with several chronic conditions
living in each different ecology and socio-economical situation. Field medicine is addressing the comprehensive geriatric issues
of community-dwelling elderly in the world using comprehensive geriatric assessment through actual medical field works.
Kozo Matsubayashi, M.D., Ph.D.
Professor
Working issues of our field medical teams are below.
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(1) Comprehensive geriatric assessment and
community-based intervention for the communitydwelling elderly in Japan.
Comprehensive geriatric assessment and
community-based intervention for the communitydwelling elderly have been carried out in Kahoku and
Tosa in Kochi, Sonobe in Kyoto, Yogo in Shiga and
Urausu in Hokkaido.
(2) Comprehensive geriatric assessment for the
community-dwelling elderly in Asia.
Cross-sectional comprehensive geriatric assessment
for the community-dwelling elderly have been
carried out in Korea, West Java in Indonesia,
Vietnam, Laos and Myanmar.
(3) Medical research for nerurodegenerative diseases
in West Papua.
We have carried out medical field research
for amyotrophic lateral sclerosis and
Parkinson·Demantia complex disease in West Papua
(Irianjaya) in Indonesia detecting some above
patients. Future study is needed for etiological
assessment.
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●
❶ A scene of CGA in West Java in Indonesia.
❷ Home visit patients living in a house on the tree, in West Papua.
Recent Publications
Field Medicine
Professor : Kozo Matsubayashi
TEL
: +81-75-753-7368
FAX
: +81-75-753-7168
e-mail
: [email protected]
URL
Kyoto University
1. Matsubayashi K et al. Mood Disorders in the Community-Dwelling Elderly in Asia. J Am Geriatr
Soc, 58 (1);213-214, 2010.
2. Matsubayashi K et al. ,Changing attitudes of elderly Japanese toward disease. J Am Geriatr Soc.
57 (9), 1732-1733, 2009.
3. Kimura Y et al. Comprehensive geriatric assessment of elderly highlanders in Qinghai, China IV:
Comparison of food diversity and its relation to health of Han and Tibetan elderly. Geriatr Gerontol
Int 9 (4):359-365, 2009.
4. Okumiya K et al. Improvement in obesity and glucose tolerance in elderly people after lifestyle
exchange 1 year after an oral glucose tolenrance test in a rural area in LAO People’s Democratic
Republic. J Am Geriatr Soc 56: 1582-1583, 2008.
5. Fujisawa M et al. Trends in diabetes. Lancet 369:1257, 2007
- Reprogramming Science - Center for iPS Cell Research and Application (CiRA)
The generation of induced Pluripotent Stem (iPS) cells with four defined transcription factors has led to the expectation that
we will be able to better understand various pathologies, and discover new drugs by using cells obtained from patients, and
thereby be able to carry out successful medical transplantation. However, before this new treatment modality can be clinically
applied, strict evaluations must be performed while always maintaining patient safety as the first priority. To this end, we have
tried to identify the optimal reprogramming factors, while continually improving the methods for iPS cell generation, and also
establish effective evaluation methods to ensure the safety of iPS cells. At the same time, we have also focused our attention on
the molecular mechanisms underlying the reprogramming process. At the end of the day, we would like to positively contribute
to the achievement of successful regenerative medicine utilizing pluripotent stem cells based on the steady accumulation of
knowledge in this important field of study.
We previously were able to successfully transform
fibroblasts into a pluripotent state using a set of four
defined transcription factors (Oct3/4, Sox2, Klf4 and
c-Myc) by means of retroviral transduction. These
artificially established cells have both potentials and
characteristics similar to those of embryonic stem
(ES) cells, and thus are called induced Pluripotent
Stem (iPS) cells. Because human iPS cells are
expected to become useful tools for both better
understanding various pathologies, as well as for
the discovery of new drugs, this technology has thus
been rapidly evolving. In addition, iPS cells are also
a potentially useful source for cell transplantation
without any danger of immunological rejection. We
have conducted numerous analyses to improve the
quality of iPS cells. According to previous results,
we have identified several issues regarding iPS cells
which still have to be overcome before they can be
used for clinical application. We believe that it is
important to understand the molecular mechanisms
underlying the reprogramming process and the
network of pluripotency for the achievement of our
ultimate goal, namely the generation of clinicalgrade iPS cells. Our field consists of seven groups,
and each of them has a unique standpoint and
background. By utilizing fusion, molecular and
cellular biology techniques and bioinformatics, we
have been continually evaluating the bottom line
of reprogramming and pluripotency from various
perspectives. At the end of the day, our results are
expected to positively contribute to the identification
of the best sources and methods for iPS cell
generation, while also establishing stable culture
conditions for effective clinical application.
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Shinya Yamanaka M.D., Ph.D.
Professor
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❶ Human iPS cells generated with L-Myc (upper photo). Germline transmission of mouse
L-Myc iPS cells (lower photo).
❷ Human iPS cells derived from adult human dermal fibroblasts.
❸ Cartilage derived from iPS cells putatively homozygous for the HLA-A, B, and DRB1 loci.
Recent Publications
Reprogramming Science, Center for iPS Cell
Research and Application (CiRA)
Professor : Shinya Yamanaka
TEL
: 075-366-7044
FAX
: 075-366-7042
e-mail
: [email protected]
URL
: http://www.cira.kyoto-u.ac.jp:80/
yamanaka_group/?lang=en
1. Nakagawa, M., Takizawa, N., Narita, M., Ichisaka, T., and Yamanaka, S. Promotion of direct
reprogramming by transformation-deficient Myc. Proc Natl Acad Sci U S A. 107(32):14152-14157,
2010.
2. Yoshida, Y., Takahashi, K, Okita, K., Ichisaka, T., and Yamanaka, S. Hypoxia Enhances the
Generation of Induced Pluripotent Stem Cells. Cell Stem Cell 5:237-241, 2009.
3. Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., and
Yamanaka, S. Suppression of induced pluripotent stem cell generation by the p53–p21 pathway.
Nature 460: 1132-1135, 2009.
4. Miura, K., Okada, Y., Aoi, T., Okada, A., Takahashi, K., Okita, K., Nakagawa, M., Koyanagi, M.,
Tanabe, K., Ohnuki, M., Ogawa, D., Ikeda, E., Okano, H., and Yamanaka, S. Variation in the safety
of induced pluripotent stem cell lines. Nature Biotechnology 27: 743-745, 2009.
5. Okita, K., Nakagawa, M., Hong, H., Ichisaka, T., and Yamanaka, S. Generation of mouse induced
pluripotent stem cells without viral vectors. Science 322: 949-953, 2008.
- Cell Growth and Differentiation - Center for iPS Cell Research and Application (CiRA)
The objective of this department is to disclose the molecular mechanisms of differentiation from induced pluripotent stem (iPS)
cells into various types of tissue cells and to establish efficient and safe induction methods, which will contribute to the clinical
application of iPS cells.
Junya Toguchida, M.D., Ph.D.
Professor
iPS cells can be applied for various clinical fields
including the investigation of pathogeneses of
diseases, the discovery of drugs, and the cell therapy.
For these applications, it is essential to establish
the methods by which iPS cells can be efficiently
and safely differentiated into target tissue-specific
cells. Based on the information of the developmental
biology, various culture conditions are employed to
establish the most suitable method of differentiation
induction. Current target cells include mesenchymal
cells such as bone, cartilage, and muscles cells,
cardiovascular cells, neural cells, and renal,
pancreatic, and hepatic cells. Principal investigators
for each part are responsible for the education of
students, and the mutual exchange of information
within the department is designed to expand the
research field of each student.
❶
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❸
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Department of Cell growth and Differentiation
Group Leader
Professor : Junya Toguchida
Associate
Professor : Jun Takahashi, Jun Yamashita,
Kenji Osafune
TEL
: +81-75-751-4134
FAX
: +81-75-751-4646
e-mail
: [email protected]
URL
: http://www.cira.kyoto-u.ac.jp/j/index.
html
Kyoto University
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❹
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❶ Cartilage-like tissue
induced from human
iPS cells
❷Dopaminergic
neurons induced
from human iPS cells
❸ Cardiomyocytes
induced from human
iPS cells
❹ Vascular structures
induced from mouse
iPS cells
❺ Hepatocytes induced
from human iPS cells
❻ Pancreatic precursor
cells induced from
human iPS cells
❻
●
Recent Publications
1. Shibata K, Toguchida J, et al. Expression of the p16INK4A gene is associated closely with
senescence of human mesenchymal stem cells, and potentially silenced by DNA methylation during
in vitro expansion. Stem Cells 25:2371-82 (2007)
2. Wataya T, Takahashi J, et al. Minimization of exogenous signals in ES cell culture induces rostral
hypothalamic differentiation. Proc Natl Acad Sci USA 105: 11796-801 (2008)
3. Narazaki G, Yamashita JK et al. Directed and systematic differentiation of cardiovascular cells
from mouse induced pluripotent stem cells. Circulation 118: 498-506 (2008)
4. Chen S, Osafune K, et al. A small molecule that directs differentiation of human ESCs into the
pancreatic lineage. Nat Chem Biol 5: 258-65 (2009)
- Clinical Application - Center for iPS Cell Research and Application (CiRA)
Disease modeling with patient-derived iPS cells
At our laboratory, we are studying the pathophysiology and pathogenesis of various intractable disease by using patient-derived
iPS cells, aiming at with a goal of applying iPS cells to clinical studies. For, efficient research on disease-specific iPS cells, it is
necessary to establish and combine the following three experimental systems appropriately: (1) establishment of disease-specific
iPS cells, (2) development of an optimal differentiation system capable of reflecting the features of disease, and (3) analysis of
differentiation-induced cells. We are interested in and studying the congenital diseases including hematological diorders with
bone marrow failure, primary immunodeficiency diseases, refractory pediatric neurological diseases, and congenital hearing
loss1.
*1 In collaboration with Prof. Juichi Ito of department of Otolaryngology, Graduate School of Medicine Kyoto University
Tatsutoshi Nakahata M.D., Ph.D.
Professor
We have already established more than 20 patientderived iPS cells with 8 kinds of hematological,
immunological, or neurological diseases2
(including clones now being established). Some
of these diseases have the biological features
which make generation of iPS cells very difficult.
We are enthusiastically trying to generate iPS
cells associated with these diseases, because
establishment of iPS cells from these patients will
contribute to elucidating the mechanism of cellular
reprogramming.
We are working for improving hematopoietic cell
differentiation systems and have established an
original differentiation system which can recapitulate
in vivo differentiation pathway. We use this system
for disease modeling and analysis because it can
generate various kinds of functional blood cells
such as red blood cells, neutrophils, and platelets.
Moreover, we are establishing in vivo reconstitution
system for iPS cell-derived hematopoietic cells by
transplanting them into immune-deficient NOG
mice. In vitro differentiation systems for iPS cells
into functional neurons or inner ear cells are also
under development.
Our goal is to elucidate pathophysiology of various
diseases by using iPS cell-derived functional cells or
tissues via appropriate differentiation systems. Since
patient-derived iPS cells are considered as an useful
tool for developing therapeutic drugs for intractable
diseases, we will conduct screening of drugs and
compounds which can alleviate in vitro phenotype,
in order to contribute to management of patients
suffering from intractable diseases.
*2 including clones established in collaboration with
Dr. Isao Asaka or Dr. Haruhisa Inoue, Center for iPS
cell research and application, Kyoto University
Professor
TEL
FAX
e-mail
: Tatsutoshi NAKAHATA
: +81-75-366-7033
: +81-75-366-7091
: [email protected]
Assistant
Professor
TEL
FAX
e-mail
URL
: Megumu Saito
: +81-75-366-7085
: +81-75-366-7088
: [email protected]
: http://www.cira.kyoto-u.ac.jp/nakahata/
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❶ Hematopoietic
mesodermal
colony
❷ Hematopoietic
colonies
❸ Blood cells
❹ Very immature
hematopoietic
colonies
❺ Lab members
❺
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Recent Publications
1. Sakai H, Ito S, Nishikomori R, Takaoka Y, Kawai T, Saito M, Okafuji I, Yasumi T, Heike T,
Nakahata T. : A case of early-onset sarcoidosis with a six-base deletion in the NOD2 gene.
Rheumatology (Oxford). 49: 194-196, 2010.
2. Mizuno Y., Chang H., Umeda K., Niwa A., IwasaT., Awaya T., Fukada S., Hiroshi Yamamoto H.,
Yamanaka S., Nakahata T., Heike T.: Generation of skeletal muscle stem/progenitor cells from
murine induced pluripotent stem cells. FASEB J. 24:2245-2253, 2010.
3. Kuroda Y., Kitada M., Wakao S., Nishikawa K., Tanimura Y., Makinoshima H., Goda M., Akashi
H., Inutsuka A., Niwa A., Nabeshima Y., Nakahata T., Nabeshima Y., Fujiyoshi Y., Dezawa M.:
Unique multipotent cells in adult human mesenchymal cell populations. Proc. Natl. Adad. Sci. USA
107:8639-8643, 2010.
4. Kumada T., Yamanaka Y., Kitano A., Shibata M.,Awaya T., Kato T., Okawa K.,Abe T., Oshima N.,
Nakahata T., Heike T.: Ttyh1, a Ca2+-binding protein localized to the endoplasmic reticulum, is
required for early emblyonic development. Develop. Dynam. 239:2233-2245,2010.
5. Kaichi S., Hasegawa K., Takaya T., Yokoo N., Mima T., Kawamura T., Morimoto T., Baba S., Doi
H., Yamanaka S., Nakahata T., Heike T.: Cell line-dependent differentiation of induced pluripotent
stem cells into cardiomyocytes in mice. Cardiovascular Res. 88: 314-323, 2010
- Kyoto University Health Service
Preventive Services
Caring for the ill persons is the origin of medicine. Prevention of disease is another matter of importance. Prevention includes
preventing the occurrence of a disease (primary prevention) and arresting the progression of a disease through early diagnosis
and early treatment (secondary prevention). Kyoto University Health Service is the primary-care facility for preventive services,
such as health checkups and promotion, for students and employees of Kyoto University. We also provide health guidance and
counseling as well as primary care for diseases and injuries. In our practice, we conduct epidemiological research for disease
control and prevention, and develop various healthcare systems. In this way, we disseminate evidence from the on-site daily
clinical routine.
Takashi Kawamura, M.D., Ph.D.
Professor
“Sudden death of employees frequently occurs
in April and on weekends.” “Water-gargling
prevents common cold.” ”Chest compression-only
resuscitation is the best way for lay bystanders.”
“Introduction of hemodialysis in IgA nephropathy
can be predicted by blood pressure, urine protein,
urine blood, serum albumin, etc.” ”Adverse events ❶ Randomized controlled
t r i a l eva l u a t i n g t h e
of gefitinib are more common among patients
preventive effect of
with some characteristics.” We are studying quite
gargling for common
common health problems to contribute to daily
cold (Ref No.2)
healthcare. Our study tool is epidemiology. We ❷ Patients cohort study
identifying the risk
collaborate with many medical and governmental
fa c t o r s o f a d v e r s e
facilities all over the country.
events by gefitinib (Ref
In the School of Public Health, we participate in a
No.5)
core-course on “Epidemiology” which helps us to
evaluate the causes of a disease and the effectiveness
of medical procedures through observation and
intervention, and also in courses on ”Study protocol
writing and study management” and ”Cardinal points
in clinical research practice” for students who intend
to carry out clinical researches. We continuously
mentor each student assigned to our department. As a
graduate school student, some medical qualifications
are required because we study in practices. See the
webpage of the University Health Service.
Preventive Services
(Kyoto University Health Service)
Professor : Takashi Kawamura
Associate
Professor : Kazumi Takemoto, Masahiko Ando
Senior
Lecturer : Masashi Goto
Assistant
Professor : Taku Iwami, Teruhisa Uwatoko
TEL
: +81-75-753-2400
FAX
: +81-75-753-2424
e-mail
: [email protected]
URL
: http://www.kyoto-u.ac.jp/health/kuhchome.html
Kyoto University
❶
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Recent Publications
1. Kawamura T, Kondo H, Hirai M, et al. Sudden death in the working population: a collaborative
study in central Japan. Eur Heart J 1999; 20: 338-343.
2. Satomura K, Kitamura T, Kawamura T, et al. Prevention of upper respiratory tract infections by
gargling: a randomized trial. Am J Prev Med 2005; 29: 302-307.
3. Iwami T, Kawamura T, Hiraide A, et al. Effectiveness of bystander-initiated cardiac-only
resuscitation for patients with out-of-hospital cardiac arrest. Circulation 2007; 116: 2900-2907.
4. Goto M, Kawamura T, Ando M, et al. A scoring system to predict renal outcome in IgA
nephropathy: a nationwide 10-year prospective cohort study. Nephrol Dial Transplant 2009; 24:
3068-3074.
5. Ando M, Okamoto I, Yamamoto N, et al. Predictive factors for interstitial lung disease, antitumor
response, and survival in non-small cell lung cancer patients treated with gefitinib. J Clin Oncol
2006; 24: 2549-2556.
- Institute for Integrated Cell-Material Sciences (iCeMS)
How can our body be created from a single cell, the egg? What defines totipotency in the egg? Seeking for answers to these
questions, our current projects focus on understanding the mechanism by which the initial asymmetry is established in the
mammalian embryo. Direct observation of dynamic morphogenesis is a central feature of our research, and we adopt multidisciplinary strategies for a systems-level understanding of mammalian development. Your will study in an international
environment, collaborating with laboratories in the Max-Planck Institute (http://www.mpi-muenster.mpg.de/en/index.html) and
European Molecular Biology Laboratory (EMBL : http://www.embl.de/).
Takashi Hiiragi, M.D., Ph.D.
Professor
The ultimate goal of the research in our laboratory
is the understanding of totipotency: what defines
totipotency and what makes cell totipotent. Germline cells, oocyte and sperm, are highly differentiated
but nevertheless able to regain totipotency by
forming a zygote, thereby initiating embryonic
development in the next generation. A prerequisite
for understanding totipotency is the knowledge of
developmental mechanisms during transition from
oocyte to embryo and early embryogenesis. Our
current research thus focuses on a systems-level
understanding of the principles underlying early
mammalian development.
We adopt a wide variety of experimental approaches
in order to understand the program at a molecular,
cellular and systems level; in particular, 4D liveimaging, fluorescence-based gene-trap screen,
gene expression profile of individual blastomeres,
experimental micromanipulation and computer
simulation of the blastocyst morphogenesis.
Questions to be addressed in your PhD study include:
- When and how is the initial lineage established in
the mouse embryo?
- How can the mouse embryo count its
developmental timing?
See http://www.embl.de/ for detail.
❶
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❶ Totipotent egg
❷ Blastocyst morphogenesis
❸ Computer simulation of blastocyst morphogenesis
❹ ICM-specific reporter expression in a gene-trap
mouse
❹
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Recent Publications
Professor : Takashi Hiiragi
TEL
: +81-75-753-9844
FAX
: +81-75-753-9820
e-mail
: [email protected]
URL
: http://www.icems.kyoto-u.ac.jp/e/ppl/
grp/hiiragi.html
1. Honda, H., Motosugi, N., Nagai, T., Tanemura, M. and Hiiragi, T. (2008). Computer simulation of
emerging asymmetry in the mammalian blastocyst. Development 135:1407-1414.
2. Dietrich, J.-E. and Hiiragi, T. (2007). Stochastic patterning in the early mouse embryo.
Development 134:4219-4231.
3. Motosugi, N., Dietrich, J-E., Polanski, Z., Solter, D. and Hiiragi, T. (2006). Space asymmetry
directs preferential sperm entry in the absence of polarity in the mouse oocyte. PLoS Biology
4:e135.
4. Motosugi, N., Bauer, T., Polanski, Z., Solter, D. and Hiiragi, T. (2005). Polarity of the mouse
embryo is established at blastocyst and is not prepatterned. Genes & Development 19:1081-1092.
5. Hiiragi, T. and Solter, D. (2004). First cleavage plane of the mouse egg is not predetermined but
defined by the topology of the two apposing pronuclei. Nature 430:360-364
- Affiliate Graduate School - RIKEN Center for Developmental Biology
Medical Embryology
Laboratory for Organogenesis and Neurogenesis
Brain development itself is a great mystery, which has been enhanced scientists for many decades. Recent progress in molecular
embryology has isolated a huge number of regulatory genes involved in this process. This department focuses on molecular and
cellular mechanism of the regional specificity in developing brain tissues. This exciting field of research is also contributing to
the progress of regenerative medicine, especially ES cell-based therapeutics of neurological diseases.
Yoshiki Sasai, M.D., Ph.D.
Kyoto University Visiting Professor
By using the affiliation graduate school system,
Kyoto University and RIKEN Center for
Developmental Biology cooperate in education and
training of graduate students. We also hold a summer
intensive course for developmental and regeneration
study together at RIKEN.
■Focus 1
"Induction and Early Patterning of Vertebrate Neural
Tissues"
We wish to understand the molecular and cellular
bases of vertebrate neural induction (i.e., the initial
step of neurogenesis) and early ectodermal patterning
following the primary induction. For this reaserch,
the primary experimental animal we use is Xenopus.
❶
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"Secreted Patterning Signals that Provide Positional
Information in CNS Development"
We wish to identify new patterning signals that give
positional information to differentiating neural cells
in the central nervous system (CNS), and analyzed
their in vivo roles. We use Xenopus, chick and mice
for this study.
"Establishment of in vitro Neural Differentiation
Systems Using ES Cells"
By using mouse ES cells, we attempt to establish ❶ Dopaminergic neurons (yellow)
and other neurons (red) induced
efficient in vitro systems of neural differentiation that
from primate ES cells by the SDIA
mimics mammalian neurogenesis. By using these
method.
systems, we wish to understand signals that define ❷ Expression of the CNS marker Sox2
the positional identity of cells in the embryonic
(blue) and the neural crest marker
FoxD3 (indigo) in the Xenopus
nervous systems.
neur ula. We have proved that
Sox2 and FoxD3 are essential for
development of the CNS and the
neural crest, respectively.
❸ Discussion on data
"Application of in vitro Produced Neural and
Sensory Cells to Regenerative Medicine"
The goal of this study is to establish the technical
bases of the production of neurons to be used
in regenerative medicine for diseases, such as
Parkinson’s disease and retinal degeneration. This Recent Publications
topic is studied in close collaboration with Kyoto 1. Eiraku, M, Watanabe, K., Matsuo-Takasaki, M., Kawada, M., Yonemura, S., Matsumura, M.,
Wataya, T., Nishiyama, A., Muguruma, K. and Sasai, Y. (2008) Self-Organized Formation of
University Hospital.
Medical Embryology
Laboratory for Organogenesis and
Neurogenesis
RIKEN Center for Developmental Biology
Group
Director : Yoshiki Sasai
TEL
: +81-78-306-1841
FAX
: +81-78-306-1854
e-mail
: [email protected]
URL
: http://www.cdb.riken.jp/sasai/
Kyoto University
Polarized Cortical Tissues from ES cells and its Active Manipulation by Extrinsic Signals. Cell
Stem Cell 3, 519-532
2. Inomata, H., Haraguchi, T. and Sasai, Y. (2008) Robust Stability of the Embryonic Dorsal Axial
Pattern Requires ONT1, a Secreted Scaffold for Chordin Degradation. Cell 134, 854-865.
3. Sasai, N., Yakura, R,, Kamiya, D., Nakazawa, Y. and Sasai, Y. (2008) Ectodermal Factor Restricts
Mesoderm Differentiation by Inhibiting p53. Cell 133, 878–890
4. Muguruma, K., Nishiyama, A., Ono, Y., Miyawaki, H., Mizuhara, E., Hori, S., Kakizuka, A.,
Obata, K., Yanagawa, Y., Hirano, T. and Sasai, Y. (2010) Ontogeny-recapitulating generation and
tissue integration of ES cell-derived cerebellar Purkinje cells. Nature Neurosci 13, 1171 - 1180
5. Kamiya, D., Banno, S., Sasai, N., Watanabe, K., Kawada, M., Yakura, R., Jakt , L.M., Nishikawa,
S. and Sasai. Y. (2011) Intrinsic transition of ES cell differentiation into neural progenitors. Nature
470, 503-509
Laboratory for Genomic Reprogramming
We use the mouse as a model system to study cloning under a range of experimental conditions with the goals of achieving
improvements in the efficiency of the cloning procedure, gaining a better understanding of reprogramming mechanisms and
analyzing the properties of ES cells derived via somatic nuclear transfer. We also use nuclear transfer technology to develop
methods for preserving embryonic lethal and infertile strains of laboratory mice, and continue to explore the development of new
and better techniques for sperm and oocyte preservation and other reproductive biological research technologies.
Teruhiko Wakayama, Ph. D.
Kyoto University Visiting Associate Professor
Our general research interest is to elucidate how a
completely differentiated cell can be reprogrammed
by oocyte cytoplasm and develop to full term.
Gamete cells themselves are of course also
differentiated and highly specialized cells that
function in the generation of offspring, and these
cells (spermatozoa and oocytes) do not exhibit
totipotency until fertilization. After fertilization,
the nuclei of both the sperm and the oocyte are
reprogrammed and gain totipotency within the
cytoplasm of the oocyte. We have hypothesized
that, in cloning experiments, somatic cell nuclei
undergo reprogramming in an unfertilized oocyte in
a manner similar to that of gametes in fertilization;
the oocytes ability to reprogram somatic cell nuclei
seems otherwise inexplicable. For this reason,
although our main research interest is somatic cell
nuclear transfer, we are also working to clarify the
mechanisms of gametogenesis and fertilization, a
better understanding of which would seem likely
help us to gain insight into the mechanisms of nuclear
reprogramming and animal cloning. We are also
interested in the development of new techniques for
the production of offspring from immature gametes
or infertile mice lacking germ cells, as well as for
the preservation of gamete cells without freezing,
as the development of such techniques may help us
to extend our ability to conduct experiments. Our
ongoing projects are detailed below, organized into
four foci.
❶
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Laboratory for Genomic Reprogramming
Team
Leader
: Teruhiko Wakayama
TEL
: +81-78-306-3049
FAX
: +81-78-306-3095
e-mail
: [email protected]
URL
: http://www.cdb.riken.go.jp/grp/
Recent Publications
❶ N u c l e a r t r a n s fe r ; M o u s e
oocyte was fixed by holding
pipette and donor somatic
nucleus was injected into
oocyte by micromanipulator.
❷ Mouse frozen at -20oC for 16
years
❸ Healthy cloned mouse derived
from the frozen mouse
❹ Abnormality of cloned mice.
Left is cloned mouse and its
placentomegaly.
❺ Lab personnels
❷
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1. Wakayama et al. (2005) Propagation of an Infertile Hermaphrodite Mouse Lacking Germ Cells,
Using Nuclear Transfer and Embryonic Stem Cell Technology. Proc. Natl. Acad. Sci. USA 102:2933. (Cover article of issue)
2. Wakayama et al., (2007) Establishment of mouse embryonic stem cell lines from somatic cell
nuclei by nuclear transfer into aged, fertilization-failure mouse oocytes. Curr Biol. 17: R120-R121
3. Tabar et al., (2008) Therapeutic cloning in individual parkinsonian mice. Nat. Med. 14: 379-381
4. Wakayama et al., (2008) Production of healthy cloned mice from bodies frozen at -20°C for 16
years. Proc Natl Acad Sci U S A. 105:17318–17322
- Affiliate Graduate School - Osaka Bioscience Institute
More than a hundred thousand of neurons reside in the human brain. These enormous numbers of neurons are variable in terms
of their morphologies, gene expressions, neurotransmitter types and functions. How is the information to control both precise
identities of these neurons and formation of complicated neural networks programmed on our DNA? How does each neuron
and glia choose their cell fate from common progenitors? How does each neuron precisely recognize other neurons and form
correct synapses? How does each neural circuit realize physiological function and behavior? Finally, how is malformation or
dysfunction of these steps related to our diseases? We are challenging these problems by using the retina as a model system to
explore the CNS. Our main technical approaches are molecular biology, histology, physiology, and mouse molecular genetics
using KO/transgenic mice including BAC transgenic and conditional KO mice.
Takahisa Furukawa, M.D. Ph.D.
Kyoto University Visiting Professor
❶
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1.Molecular mechanisms of synapse formation in the retina and
brain
2.Molecular mechanisms of primary cilia formation and
function in the CNS
3.Mechanisms of cell fate determination of the vertebrate retina
4.Functional analysis of microRNA expressed in the retina and
brain
5.Generation of KO/transgenic mice and analysis of their visual
function
It is important for research training to work under a good
mentor, absorb both basic and leading-edge knowledge in the
field, learn how to design experiments, acquire experimental
skills, analyze data, and learn how to write a paper.
1. Training of in vivo experiments
We perform various in vivo experiments to clarify gene
function. Unless you understand importance of a molecule in
vivo, you may be not sure why you study that molecule.
2. Learning various experimental skills
In our lab, we use broad range of experimental techniques
including molecular biology, histology, cell culture and
animal experiments (transgenic mouse, KO mouse, zebrafish).
Therefore, graduate students can do a good training through
learning these techniques and experiments.
3. Acquirement of broad range of knowledge
We do reading circle of textbooks and research papers. We want
to encourage young scientists to learn about various fields. That
is important for your future when you start your own research.
4. Graduate school student/postdoc from abroad
We welcome graduate school students and postdocs from
outside Japan to our lab. I am an adjunct professor of Kyoto
University Graduate School of Medicine. An applicant can
apply for either or both of these graduate schools. An applicant
needs to find a fellowship. We are happy to support applicants
to apply for a JSPS/MEXT fellowship or other available
fellowships.
Osaka Bioscience Institute
Head
: Takahisa Furukawa
Vice-Head : Yoshihiro Omori
Research
Associate : Koji Terada, Akishi Onishi
Postdoctoral
Associate : Yuki Muranishi
Research Collaborator
: Rikako Sanuki, Kimiko Katoh
Graduate
Student
: Fumiyuki Araki, Koji Mizuhashi,
Shoichi Irie, Taro Chaya,
Satoshi Watanabe
Technical
Assistant : Akiko Tani, Mikiko Kadowaki,
Toshinori Tsujii, Aiko Ishimaru,
Yukiko Saioka
TEL
: +81-6-6872-4853
FAX
: +81-6-6872-3933
e-mail
: [email protected]
URL
: http://www.obi.or.jp/dept4/english.html
Kyoto University
❷
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❶ Analysis of rod ribbon synapse in the pikachurin KO retina by electron tomography.
In the pikachurin KO retina, bipolar dendritic terminus did not invaginate into the
photoreceptor ribbon synapse.
❷ Lab members
Recent Publications
1. Omori, Y., Chaya, T., Katoh, K., Kajimura, N., Sato, S., Muraoka, K., Ueno, S., Koyasu, T., Kondo,
M. & Furukawa, T.
Negative regulation of ciliary length by ciliary male germ cell-associated kinase(Mak) is required
for retinal photoreceptor survival. Proc. Natl. Acad. Sci. U.S.A. 107(52), 22671-22676 (2010)
2. Katoh, K., Omori, Y., Onishi, A., Sato, S., Kondo, M. & Furukawa, T.
Blimp1 suppresses Chx10 expression in differentiating retinal photoreceptor precursors to ensure
proper photoreceptor development. J. of Neurosci. 30(19), 6515-6526 (2010)
3. Koike, C., Obara, T., Uriu, Y., Numata, T., Sanuki, R., Miyata, K.,Koyasu, T., Ueno, S., Funabiki,
K., Tani, A., Ueda, H., Kondo, M., Mori Y.,Tachibana, M. & Furukawa, T.
TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade.
Proc. Natl. Acad. Sci. USA, 107, 332-337 (2009)
4. Sato, S., Omori, Y., Katoh, K., Kondo, M., Kanagawa, M., Miyata, K.,
Funabiki, K., Koyasu, T., Kajimura, N., Miyoshi, T., Sawai, H., Kobayashi,K., Tani, A., Toda, T.,
Usukura, J., Tano, Y., Fujikado, T. & Furukawa, T.
Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation. Nat.
Neurosci., 11, 923-931 (2008)
5. Nishida, A., Furukawa, A., Koike, C., Tano, Y., Aizawa, S., Matsuo, I. &Furukawa, T.
Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nat.
Neurosci. 6, 1255-1263 (2003)
Application biology and regenerative medicine
laboratory for Retinal Regeneration
The retina has been called the "approachable part of the brain," owing to its relatively simple structure and its location near the
body surface, and for these reasons it serves as a useful and experimentally amenable model of the central nervous system. Until
very recently, it was thought that, in adult mammals, the retina was entirely incapable of regenerating, but we now know that
at least new retinal neurons can be generated after being damaged. This has opened up new hope that the ability to regenerate
neurons and even to reconstitute the neural network may be retained in the adult retina. We are now exploring the exciting
prospect that, by transplanting cells from outside of the retina or by regeneration from intrinsic progenitor cells, it may one day
be possible to restore lost function to damaged retinas.
Masayo Takahashi,M.D.,Ph.D.
Kyoto University Visiting Associate Professor
Our research into retinal regeneration seeks to
achieve clinical applications by developing methods
for inducing stem cells to differentiate into retinal
neurons and pigmented epithelial cells in sufficient
quantities for use in the treatment of patients
suffering from conditions in which such cells have
been damaged or lost, and to ensure that such cells
establish viable grafts on transplantation and induce
the reconstitution of functional neural networks.
We also hope to develop means of promoting true
regeneration by activating endogenous stem cells
to replace cells lost to trauma or disease and thus
repair damaged tissues. Access to a broad spectrum
of developmental biological research information
will be key to the achievement of these goals, and
we appreciate the opportunities for exchange that
working in the environment provided by the RIKEN
CDB provides.
Therapeutic applications cannot be developed
from basic research alone; the clinical approach a thorough understanding of the medical condition
to be treated - is equally important. For conditions
such as retinitis pigmentosa, even the successful
transplantation of cells in animal models may not
necessarily be translatable to a human clinical
therapy without an understanding of the underlying
genetics and possible immunological involvement.
Our goal is to study retinal regeneration based on
both a strong foundation in basic research and solid
clinical evidence.
❶
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❷
●
❸
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❶ Newly generated photoreceptor cells in
the damaged adult rat retina
❷ photoreceptor cells differentiated from
human ES cells
❸ human iPS cells
Application biology and regenerative medicine
Laboratory for Retinal Regeneration
Team Leader : Masayo Takahashi
Research
Scientist : Michiko Mandai, Kohei Homma,
Akiko Suga, Zi-Bing Jin
TEL
: +81-78-306-3305
FAX
: +81-78-306-3303
e-mail
: [email protected]
URL
: http://www.retinastem.jp/xoops/
Recent Publications
❹
●
1. Takahashi M, et al. Widespread integration and survival of adult-derived neural progenitor cells in
the developing optic retina. Mol. Cell. Neurosci. 12:340-348. 1998
2. Haruta et al. Induction of photoreceptor-specific phenotypes in adult mammalian iris tissue. Nat
Neurosci. 4:1163-1164 2001
3. Ooto et al. Potential for neural regeneration after neurotoxic injury in the adult mammalian retina.
Proc Natl Acad Sci USA. 101:13654-13659. 2004
4. Osakada F et al. Toward the generation of rod and cone photoreceptors from mouse, monkey and
human embryonic stem cells. Nat Biotech. 26:215-224. 2007
5. Zin JB et al. Identifying pathogenic genetic background of simplex or multiplex retinitis
pigmentosa patients: a large scale mutation screening study. J Med Genet. 45:465-472. 2008
- Public Health - Health Analyses
Biostatistics
Graduate students interested in the methods of biostatistics and the conduct of epidemiologic research and clinical trials are
welcomed. This Department offers programs of study leading to a master's degree and a doctoral degree. The Master of Public
Health (MPH) degree program is designed to provide basic training in biostatistics as applied to a broad spectrum of healthrelated problems. The doctoral degree program is designed to provide advanced, research oriented training in methods of
biostatistics.
T. Shun Sato, Ph.D.
Professor
❶
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Major research fields are biostatistics methodology
and conducts of epidemiologic studies and clinical
trails. In methodological work, new epidemiologic
study designs which are efficient and convenient are
investigated for providing new sampling and analysis
methods. Causal inference is the most challenging
methodological research field. Estimation of causal
parameters in experimental and observational studies
is developing. Several collaborative studies in
epidemiology and clinical trials are ongoing.
Department of Biostatistics offers “Fundamentals
of Biostatistics”, “Introduction to Statistical
Computing and Data Management”, “Intermediate
Biostatistics”, and “Health Data Processing Lab”.
We give introduction to concepts of randomization,
causal effects, and confounding, designs of clinical ❶ Biostatistics Class
trials and observational studies. Topics include
randomization, experimentation, measurement,
probability, confidence intervals, and tests of
hypotheses.
Recent Publications
Biostatistics
Professor : Tosiya Sato
Associate
Professor : Takashi Sozu
TEL
: +81-75-753-4475
FAX
: +81-75-753-4487
e-mail
: [email protected]
URL
: http://www.kbs.med.kyoto-u.ac.jp/
Kyoto University
1. Sozu T, Sugimoto T, Hamasaki T. Sample size determination in clinical trials with multiple coprimary endpoints. Statistics in Medicine 2010; 29: 2169-2179.
2. Noma H, Matsui S, Omori T, Sato T. Bayesian ranking and selection methods using hierarchical
mixture models in microarray studies. Biostatistics 2010; 11: 281-289.
3. Okusaka T, Kasugai H, Shioyama Y, Tanaka K, Kudo M, Saisho H, Osaki Y, Sata M, Fujiyama
S, Kumada T, Sato K, Yamamota S, Hinotsu S, Sato T. Transarterial chemotherapy alone versus
transarterial chemoembolization for hepatocellular carcinoma: a ramdomized phase III trail.
Journal of Hepatology 2009; 51: 1030-1036.
4. Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T, Sato T, Yamasaki K.
Randomized controlled study on the prevention of osteoporostic fractures (OF Study): A phase IV
clinical study of 15-mg menatetrenone capsules. Journal of Bone and Mineral Metabolism 2009;
27: 66-75.
5. Yonemoto N, Furuse J, Okusaka T, Yamao K, Funakoshi A, Ohkawa S, Boku N, Tanaka K, Nagase
M, Saisho H, Sato T. A multi-center retrospective analysis of survival benefits of chemotherapy for
unresectable biliary tract cancer. Japanese Journal of Clinical Oncology 2007; 37: 843-851.
Epidemiology and Healthcare Research
Clinical medicine is a highly social practice. Because it applies findings from biomedical scientific research to people living in
a complex social environment, the medical community is obliged to assess the appropriateness, effectiveness, and efficiency of
healthcare. With this in mind, we incorporate clinical medicine, epidemiology, statistics, psychometrics, and other fields into
research aimed at measuring and improving the healthcare quality and patients' outcomes. We welcome those who share our
outlook, our values, and our commitment to studying and improving clinical practice.
Shunichi Fukuhara, M.D., F.A.C.P.
Professor
What are the goals of health care? How should it
be judged? For example, the goal may be “to make
patients better", but in what sense? Surely the mere
prolongation of life is not enough. Perhaps the results
of medical-laboratory tests can be used to distinguish
success from failure, but how should we interpret
test results that are inconsistent with symptoms?
In evaluations of the effectiveness of medical
interventions, what indicators are relevant to patients
and to society?
“Quality of health care"" has become a popular topic,
but how is it defined in practice? Consider just a few
of the questions that can arise with regard to surgery:
Is comparison of death rates after surgery valid? Do
rates of post-surgical death stabilize once a certain
level of experience is reached? When evaluating
studies of post-surgical death rates, can we trust the
statistical adjustments for the severity of illness?
Our department focuses its efforts on such questions.
This field has been called “health services research".
While seeking to understand health care services
in their scientific, socio-cultural, and economic
environment, we often focus on the outcomes of
those services from the viewpoints of patients and
of society. Recent examples of our activities include
participation in an international study of dialysis
outcomes and practice patterns, and sending our
staff to the University of California (Los Angeles)
to participate in research on the quality of care
of the elderly. In cooperation with national and
international institutions, we carry out and promote
research in these and other areas with a broad
perspective and with the highest possible standards
of scientific rigor.
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Recent Publications
Epidemiology and Healthcare Research
Professor : Shunichi Fukuhara
Associate
Professor : Shin Yamazaki, Yasuaki Hayashino
Senior
Lecturer : Yosuke Yamamoto, Naoki Kakudate
Assistant
Professor : Misa Takegami
FAX
: +81-75-753-4644
URL
: http://www.epikyoto-u.jp
1. Higashi T, Wenger NS, Adams JL, et al. Patients with More Medical Conditions Receive Better
Quality Care: Analysis of data from three large surveys. New England Journal of Medicine,
356:2496-504, 2007
2. Fukuhara S, Yamazaki S, Hayashino Y, et al. Patient-reported quality of life in end-stage renal
disease. Nature Clinical Practice, 3:352-3, 2007
3. Yamazaki S, Nitta H, Ono M, et al. Intracerebral hemorrhage associated with hourly concentration
of ambient particulate matter: case-crossover analysis. Occupational Environmental Medicine,
64:17-27, 2007
4. Takegami M, Hayashino Y, Chin K, et al. Simple four-variable screening tool for identification of
patients with sleep-disordered breathing. Sleep, 32(7):939-48, 2009
5. Suzukamo Y, Fukuhara S, Green J, et al. Validation, testing of a three-component model of SF-36
scores. Journal of Clinical Epidemiology (in press 2011)
6. Hayashino Y, Fukuhara S. Diabetes in Asia. Lancet 2010;375:981-2
Pharmacoepidemiology is a natural crossing of two specialties: clinical pharmacology and clinical epidemiology. It aims to
describe, explain, predict, and control the uses and effects (beneficial and adverse events) of drugs and biologics in human
populations through the chemistry, manufacturing, and control (CMC) evaluations, non-clinical analyses, and clinical trial
design. We also perform active research and development of novel immunotoxins, cytotoxins and cancer vaccines for the
treatment of cancer.
Koji Kawakami, M.D., Ph.D.
Professor
We perform education and research on the planning,
preparation, and evaluation of clinical trials.
Researches on new drug approval and regulatory
systems in Japan, US and other countries are also
discussed. Translational research which is the
bridging of basic science to clinical application,
and the development of new therapeutics utilizing
biotechnology needs to undergo clinical trials to
evaluate their safety, tolerability, and efficacy. Drug
development requires chemistry, manufacturing,
and controls (CMC), non-clinical analyses, and
clinical protocol designs. Regulatory affairs of
pharmaceutical companies or academic institutes
work with the regulatory authority to initiate
any clinical trials. Along with the ongoing and
completion of clinical trials several issues including
data analysis, evaluation of adverse events, postmarketing evaluation processes, and comparative
effectiveness research (CER) are involved. Thus,
we educate individuals and perform research on
the entire process of drug development and clinical
usage. In addition, we initiate active research projects
on immunotoxins approach utilizing novel hybrid
peptide for the treatment of cancer and inflammation.
During the development of such biologics, on-thejob-training involving the drug safety assessment and
evaluation of drug efficacy is being performed.
Professor : Koji Kawakami, MD, PhD
Associate
Professor : Shiro Hinotsu, MD, PhD
: Tomohisa Horibe, PhD
Hisashi Urushihara, DrPH
TEL
: +81-75-753-9469
FAX
: +81-75-753-4469
e-mail
: [email protected]
URL
: http://square.umin.ac.jp/kupe/
Kyoto University
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❶ Investigational New Drug, +: New Drug Application
❷ Group picture
❸ Hybrid peptide therapeutics
❹ Immunotoxin book
Recent Publications
1. Ueyama H et al. Chromosomal variability of human mesenchymal stem cells cultured under
hypoxic condition. J. Cell Mol Med., in press, 2011.
2. Horibe T, Kohno M, Haramoto M, Ohara K, Kawakami K. Designed hybrid TPR peptide targeting
Hsp90 as a novel anticancer agent. J. Translational Med., in press, 2011.
3. Tada N et al. The current status of umbilical cord blood collection in Japanese medical centers:
survey from the obstetricians. Transfusion Apheresis Sci., in press, 2011.
4. Kohno M et al. A novel hybrid peptide targeting EGFR-expressing cancers. Eur. J. Cancer, in press,
2011.
5. Kobayashi Y, Hayashino Y, Takagaki N, Hinotsu S, Jackson JL, Kawakami K. Diagnostic
performance of chromoendoscopy and narrow band imaging for colonic neoplasms: meta-analysis.
Colorectal Dis., in press, 2011.
Study of human diseases based on genetic information in the human genome is one of the most important subjects in the
Post Genome Project. In particular, to overcome human multigenetic disorders, it is essential to perform trans-ethnic genetic
analyses of human genome variations. In our laboratory, we perform SNP identification and genotyping of candidate genes
of multigenetic diseases using DNA samples of patients and control subjects from different ethnic origins. We also work on
the construction of a comprehensive SNP database of different multigenetic diseases which integrates genetic and clinical
information using the latest bioinformatic and statistical genetic tools. We try to establish a new generation genome variationbased genomic strategy which will directly linked to clinical research and therapeutics.
Fumihiko Matsuda, Ph.D.
Professor
We have established an extensive international
collaboration for ‘Genomic Epidemiology of Human
Multigenetic Disorders’ with Centre National de
Genotypage (CNG) in France. We focus on diseases
related to the immune system such as Rheumatoid
Arthritis, Lupus, Hyperthyroidism and AIDS, and
those in which DNA repair mechanism is involved
such as cancer. We have started a systematic SNP
identification using a standard panel of DNA
samples from multiple ethnic groups (Caucasians,
Japanese, Africans, Thai). Based on the SNP catalog
obtained, we undertake a large-scale case/control
study by genotyping SNPs on an epidemiological
scale (sample scale of > 1,000 individuals). Results
are deposited in a disease-based genetic database
which contains information of genes and their
genetic variations combined with patient’s clinical
information. Extensive statistical analyses is
performed using a variety of statistical programs
developed from joint research with CNG and The
Rockefeller University in U.S.A. Comparison of
genotypes between patients and controls among
different ethnicities leads to the identification of
disease-specific and ethnicity-specific genome
variations. Annotated data will be made available to
the scientific community as basic genetic information
of diseases for future development of diagnostics and
individual-based therapy (taylor-made medicine).
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❶ Laboratry
members
Recent Publications
Professor : Fumihiko Matsuda
Associate
Professor : Hiroshi Kadotani
Associate Professor (Industry-Academia Collaboration)
: Yoshiki Murakami
Assistant
Professor : Meiko Takahashi
TEL
: +81-75-753-4661
FAX
: +81-75-753-9314
e-mail
: [email protected]
1. SEARCH Collaborative Group, Link, E., Parish, S., Armitage, J., Bowman, L., Heath, S., Matsuda,
F., Gut, I., Lathrop, M. and Collins, R. (2008) SLCO1B1 variants and statin-induced myopathy--a
genomewide study. N. Engl. J. Med. 359, 789-799.
2. McKay, J.D. et al. (2008) Lung cancer susceptibility locus at 5p15.33. Nat. Genet. 40, 1404-1406
3. Wada, M., Marusawa, H., Yamada, R., Nasu, A., Osaki, Y., Kudo, M., Nabeshima, M., Fukuda, Y.,
Chiba, T. and Matsuda, F. (2009) Association of genetic polymorphisms with interferon-induced
haematologic adverse effects in chronic hepatitis C patients. J. Viral. Hepat. 16, 388-396.
4. Nakanishi, H., Yamada, R., Gotoh, N., Hayashi, H., Yamashiro, K., Shimada, N., Ohno-Matsui, K.,
Mochizuki, M., Saito, M., Iida, T., Matsuo, K., Tajima, K., Yoshimura, N. and *Matsuda, F. (2009)
A Genome-Wide Association Analysis Identified a Novel Susceptible Locus for Pathological
Myopia at 11q24.1. PLoS Genetics Epub 2009 Sep 25.
5. Takahashi, M., Saenko, V. A., Rogounovitch T. I., Kawaguchi, T., Drozd, V. M., TakigawaImamura, H., Natallia M. Akulevich, N. M., Ratanajaraya, C., Mitsutake, N., Takamura, N.,
Danilova, L. I., Lushchik, M. L., Demidchik, Y. E., Heath, S., Yamada, R., Lathrop, M., Matsuda,
F. and Yamashita, S. (2010) The FOXE1 locus is a major genetic determinant for radiation-related
thyroid carcinoma in Chernobyl. Hum. Mol. Genet. Mar 30. [Epub ahead of print]
6. Nalpas, B., Lavialle-Meziani, R., Plancoulaine, S., Jouanguy, E., Nalpas, A., Munteanu, M.,
Charlotte, F., Ranque, B., Patin, E., Heath, S., Fontaine, H., Vallet-Pichard, A., Pontoire, D.,
Bourlière, M., Casanova, J. L., Lathrop, M., Bréchot, C., Poynard, T., Matsuda, F., Pol, S. and Abel,
L. (2010) Interferon-γ receptor 2 gene variants are associated with liver fibrosis in patients with
chronic hepatitis C infection. Gut. In the press
- Public Health - Health Administration
Healthcare Economics and Quality Management
The mission of the Department of Healthcare Economics and Quality Management is to contribute to the improvement of the
quality and efficiency of health systems by means of research, development, education and professional practice. To tackle
and solve problems of quality and cost in health and health care, the Department applies multi- and inter-disciplinary fields of
quantitative and qualitative sciences and technologies.
Yuichi Imanaka, M.D., M.P.H., Dr.Med.Sci., Ph.D.
Professor
Education and Training
To produce, in succession, and support highlyqualified researchers who leads the emerging
area of health care quality, economics, policy
and management and highly-qualified managers/
directors who directly commit themselves in the
new arena of the improvement of systems of health
care; To develop a productive and mutually growing
network with those inside and outside to improve
health and health care system through the expertise
of the network member; To systematize, improve
and establish the education and training systems for
academic and management works.
Research and Development
To produce academic research outputs contributory
to health systems improvement through establishing
more productive work systems and more
effective collaborative networks; To develop "soft
technologies" in succession on a stable basis which
are to be actually and effectively implemented in the
health policies and systems - examples are healthcare
performance indicators, casemix classification and
severity adjustment methodology, quality and safety
management standards for accreditation, costing
manuals for health care; To be a productive research
team internationally renowned in the area of health
care quality, economics, policy and management.
Degrees to be Offered
Doctor of Medical Science (DrMedSci or PhD):
It usually takes 4 years. Doctor of Public Health
Science (DrPH or PhD): It takes 3 years, usually
after MPH. Master of Public Health (MPH): It
usually takes 2 years, and also provides 1-year
course. Additional information may be found on our
Department home page.
Recent Publications
Healthcare Economics and Quality
Management
Professor : Yuichi Imanaka
Assistant
Professor : Hiroshi Ikai, Tetsuya Otsubo
TEL
: +81-75-753-4454
FAX
: +81-75-753-4455
e-mail
: [email protected]
URL
: http://med-econ.umin.ac.jp/
Kyoto University
1. Difference in lifetime medical expenditures between male smokers and non-smokers. Health
Policy. 2010 ;94(1):84-9.
2. Impact of system-level activities and reporting design on the number of incident reports for patient
safety. Quality & Safety in Health Care. 2010;19(2):122-7.
3. An outcome prediction model for adult intensive care. Critical Care and Resuscitation. 2010
;12:96-103.
4. Healthcare-associated infections in acute ischemic stroke patients from 36 Japanese hospitals: riskadjusted economic and clinical outcomes. International Journal of Stroke. 2011; 6(1):16-24.
5. Evaluation of resource allocation and supply-demand balance in clinical practice with high-cost
technologies. The Journal of Evaluation in Clinical Practice (in press)
Medical Ethics / Medical Genetics
As a department of School of Public Health (SPH), education and training of professionals who can work in new fields are
performed. Investigation of the related academic fields is simultaneously intensively done. Training of (1) professionals for
medical ethics committees and (2) Certificated Genetic Counselors (CGC) are especially focused. The CGC system began in
2005 in Japan. New course for genetic counselors and clinical research coordinators started in 2006 related with our department.
These fields are expected to increase their need a lot, along with development of advanced medicine and increase in information
of genome.
Shinji Kosugi, M.D., Ph.D.
Professor
Education:
■ Basic Medical Ethics
■ Medical Ethics
■ Fundamental human genetics
■ Clinical Genetics and Genetic Counseling
■ Genetic Medicine and Ethics
■ Genetic Medicine and Society
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❷ Small Group
Discussion
Research Subject:
■ Study on ethics committee and ethical evaluation
of research plans.
■ Study on how genetic medicine should be.
■ Study on gene diagnosis and informed consent for
genome research.
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Recent Publications
Medical Ethics/Medical Genetics
Professor : Shinji Kosugi
Associate
Professor : Hironao Numabe
Assistant
Professor : Yuri Dowa
TEL
: +81-75-753-4647
FAX
: +81-75-753-4649
e-mail
: [email protected]
1. Jin ZB, Mandai M, Yokota T, Higuchi K, Ohmori K, Ohtsuki F, TakakuraS, Itabashi T, Wada Y,
Akimoto M, Ooto S, Suzuki T, Hirami Y, Ikeda H,Kawagoe N, Oishi A, Ichiyama S, Takahashi
M, Yoshimura N, Kosugi S. Identifying pathogenic genetic background of simplex or multiplex
retinitis
2. Kei Kano, Saiko Yahata, Kaori Muroi, Masahiro Kawakami, Mari Tomoda,KoichiMiyaki, Takeo
Nakayama, Shinji Kosugi, Kazuto Kato. Multimedia Presentations on the Human Genome:
implementation and assessment of ateaching program for the introduction to genome science using
a poster and animations. Biochem Mol Biol Edu. 2008, 36:395-401
3. Yamano E, Isowa T, Nakano Y, Matsuda F, Hashimoto-Tamaoki T, Ohira H, Kosugi S. Association
study between reward dependence temperament and a polymorphism in the phenylethanolamine
N-methyltransferase gene in aJapanese female population. Comprehensive Psychiatry 2008
49:503-507.
4. Szinnai G, Kosugi S, Derrien C, Lucidarme N, David V, Czernichow P, Polak M: Extending the
clinical heterogeneity of iodide transport defect (ITD): A novel mutation R124H of the sodium/
iodide symporter (NIS) gene and review of genotype-phenotype correlations in ITD. J Clin
Endocrinol Metab,2006 Apr;91(4):1199-204. Epub 2006 Jan 17.
5. Fujita M, Akabayashi A, Slingsby BT, Kosugi S, Fujimoto Y, Tnaka K: A model of donors’
decision-making in adult-to-adult living donor liver transplantation in Japan: having no choice.
Liver Transplantation, 2006 May; 12(5):768-74.
6. Takahashi M, Kikuchi M, Ohkura N, Yaguchi H, Nagamura Y, Ohnami S, Ushiama M, Yoshida T,
Sugano K, Iwama T, Kosugi S, Tsukada T. Detection of APC gene deletion by double competitive
polymerase chain reaction in patients with familial adenomatous polyposis. Int J Oncol. 2006
Aug;29(2):413-21.
7. Itai K, Asai A, Tsuchiya Y, Onishi M, Kosugi S. How do bioethics teachers in Japan cope with
ethical disagreement among healthcare university students in the classroom? A survey on educators
in charge. J Med Ethics. 2006 May;32(5):303-8.
Health Informatics
In today’s society, the impact of health-related information on human behavior and health can be just as profound as, or in some
cases, more profound than, the impact of physical environment on human health. This field of study explores how information
can contribute to improving people’s health behavior/health-care-seeking behavior, and decision-making in community health.
The main topics to be covered are: Evidence-based healthcare (EBHC); decision analysis, health literacy & communication;
epidemiologic research including genome approach, quantitative and qualitative assessment of health-related information;
e-Health; and information ethics.
Takeo Nakayama, M.D., Ph.D.
Professor
Research and Education Epidemiology (required):
Epidemiology is the study of the distribution
of illness in populations and its application to
the control of health problems. This course will
provide students with the fundamental ideas about
methodologies and principles of epidemiology.
Literature Search (elective): This course serves as
an introduction to literature search using some of
the largest databases for citations and abstracts from
medical literature, such as PubMed, The Cochrane
Library, and the web of Japan Medical Abstracts
Society. Critical Appraisal (elective): This course
will explore not only how to examine but also how
to use a range of health-related information based on
the knowledge of epidemiology and evidence-based
medicine (EBM).
Health Informatics (elective): This course will
explore how to collect, store, communicate, retrieve,
and evaluate health-related information and data.
From the point of view of epidemiology and
EBM, this course will consider how health-related
information from various sources may differ from
each other and how such information can be used
in an effective and constructive way. Issues related
to information literacy, information sharing, and
information ethics will also be addressed. Lecture
and discussion on the status quo of advanced
medicine and a hospital tour will be provided
in collaboration with the department of clinical
medicine.
analysis of epidemiologic data (elective): This course
offers the opportunity to analyze real epidemiologic
data.
Recent Publications
Health Informatics
Professor : Takeo Nakayama
Associate
Professor : Tatsuro Ishizaki
TEL
: +81-75-753-9477
FAX
: +81-75-753-9478
e-mail
: [email protected]
URL
: http://www.healthim.umin.jp/
Kyoto University
1. Takahashi Y, et al. Potential benefits and harms of a peer support social network service on the
Internet for people with depressive tendencies: qualitative content analysis and social network
analysis. Journal of Medical Internet Research. 2009;11:e29
2. Tanaka Y, Nakayama T, Nishimori M, Sato Y. Lidocaine for preventing post-operative sore throat.
Cochrane Database Syst Rev. 2009 Jul 8;(3):CD004081
3. Nagai S, et al. Earlier versus later continuous Kangaroo Mother Care (KMC) for stable low-birthweight infants: a randomized controlled trial. Acta Paediatrica. 2010 Jan 27. [Epub ahead of print]
4. Nakaoka S, et al. Adherence in performing echocardiography to detect valvulopathy associated
with the use of ergot-derived dopamine agonists in patients with Parkinson’s disease. Internal
Medicine. (in press)
5. Mori H, et al. Characteristics of caregiver perceptions of end-of-life caregiving experiences in
cancer survivorship: in-depth interview study. Psycho-oncology. (in press)
(selected)
Medical Communication is a specialized area in medicine within science communication, which is currently enjoying
national and international public attention. Kyoto University is the first in Japan to have established a department of Medical
Communication that investigates how medical knowledge is shared and circulated among different societal segments (eg., the
public, media, policy makers, and the medical community) on a variety of levels (personal/micro, community/meso, social/
macro, and international). Medical communication, therefore, is not the same as health communication, which is a well-known
communication field researching a doctor-patient interaction, as the former has a more macro research domain. This new
department welcomes students who are eager to not only tackle the aforementioned ambitious theme but also explore and claim
the emerging field of medical communication.
First semester: In this semester, the course provides
an introduction to medical communication, both
its theoretical frameworks and applications,
for those from diverse interests, backgrounds,
and/or disciplines. In class, frames from
communication studies, disability studies, and/
or science communication are drawn, and an issue
of communication channels is addressed. Second
semester: Building upon the first semester, the
course further explores current topics in medical
communication, especially relations among the
medical/research community, media, public, and
policy makers.
Below are the course objectives:
●understand frameworks, theories, and concepts that
are relevant to medical communication
●begin to see a “niche” of your interest in a field of
medical communication and find a research question
to be explored
●understand the interconnectedness among the
medical community, media, public (including the
stakeholders or interest groups), and policy makers
●write a succinct literature review on your topic with
a critical perspective
Any research reflects a researcher’s personal history
and perspective, and my research has ranged from
intercultural communication, health communication,
to disability studies. Although they may not seem
related, I’ve always been fascinated by the world
according to a minority perspective and conducted
a series of research projects aimed at investigating
people on the margins of society. Within medical
communication, I’m interested in such topics as
bridging between the medical community and public,
aging with disability, and emancipatory research.
You may wonder “what do I become by studying
medical communication?” I offer you this analogy:
doing a rigorous study is similar to getting a roadmap on an unknown terrain. This means that the map
can help you “read” a targeted landscape or calculate
the shortest distance to the goal. Nevertheless, let me
remind you, the map itself never tells you which goal
to reach or what route to take. It’s all up to you, either
you “cut to the chase” to the goal or are sidetracked Recent Publications
by attractive views alongside of the scholastic 1. Iwakuma, M. (2007). A chronicle of my education and disability transformation. In M. L. Vance
(Ed.), Multiple Voices and Identities in Higher Education: Writings by Disabled Faculty and Staff
endeavor. I suggest that YOU design a research path
in a Disabling Society (pp. 87-95). Huntsville, NC: Associates on Higher Education And Disability.
of your own through exploring a “map” of medical
2. Iwakuma, M., & Stadnyk, R. (2007). Aging with spinal cord injury, future directions, and
communication.
Associate
Professor : Miho Iwakuma, Ph.D.
TEL
: +81-75-753-4668
e-mail
: [email protected]
implications. In Festival of International Conferences on Caregiving, Disability, and Aging and
Technology Proceedings (CD-Rom).
3. Iwakuma, M. (2007). Communication with the elderly and people with disabilities [in Japanese].
In M. Isa (Ed.), Multi-cultural Society and Intercultural Communication (2nd Edition). Tokyo:
Sanshu Press.
4. Iwakuma, M (2005). A transformation: A disability adjustment through communication [in
Japanese]. In Sakai Ikuko (Ed.), Transcendental rehabilitation (pp. 12-21). Tokyo: Bunkodo.
5. Iwakuma, M. (2003). Being Disabled in Modern Japan: A Minority Perspective. In E. M. Kramer
(Ed.), The Emerging Monoculture: “Model Minorities” and Benevolent Assimilation (pp. 124138). Praeger Press.
- Public health - Health Administration
Management of Technology and Intellectual
Property
Along with paradigm change taking place on global scale, universities are counted upon by the public on their capability in
handling these changes. Under much expectations from both industry and government sector, universities now have a role
to contribute to society by leading the development of advanced scientific technologies from basic research to industrially
applicable form.
The department aims to foster managers of intellectual property in order to promote technology transfer in life science.
Hirokazu YAMAMOTO, Ph.D.
Professor
❶ Members
❷ Entrepreneurship
Exercise
❸ Entrepreneurship
Exercise Members
As well as equipping students with practical skills, the
department teaches basic theories particularly in the field of
advanced medicine, IP low and business particularly on the
exploitation of intellectual property rights. The department aims
to nurture directors of technology management, the personnel
with the capability to discover, manage and exploit the
intellectual property in the field of biotechnology, particularly
in advanced medicine.
1.Medical Science: the department will give students toplevel scientific knowledge and the knowledge on industrial
demand through lectures by the academics who are engaged
in researches of forefront science at the graduate school
of medicine, and by the industrial professionals who hold
abundant experience in translational research and development
research in the industry.
2.IP Law and Business: the department will give students
basic knowledge of intellectual property laws and life science
industry through lectures by instructors selected for each
specialization field. The practical skills and knowledge in
accounting and market valuation and distribution of intellectual
property are taught through lectures by lecturer with a long
career in business such as venture capital.
3.Practical Skills: Using the knowledge learned above as a
base, the department will equip students with ability to act in
real situation through work experience at Kyoto University and
through other externships, gaining experience in establishing
rights in research out come and in exploitation of those rights.
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At the Management of Technology and Intellectual Property,
we are being conducted on various problems faced in
management and practical application of intellectual property
rights. So far, research has been conducted on “Investigation for
protection and utilization of intellectual property in translational
research for purpose of establishing the management system”
and “Systems of intellectual property management which can
accommodate movement of researchers from one institution to
another”. The findings from these researches are reflected in the
management of intellectual property at Kyoto University.
Management of Technology and Intellectual
Property
Professor : Hirokazu Yamamoto
Professor (Special Appointment)
: Yutaka teranishi
Professor : Seiji Abe
Associate
Professor : Chikako Saotome
Part-time
Lecturer : Ken-ichi Kumagai, Hideho Tanaka,
Atsushi Fujii
Assistant
Professor : Tomochika Aono
TEL
: +81-75-753-9332
FAX
: +81-75-753-9333
e-mail
: [email protected]
URL
: http://www.motkyoto.com
Kyoto University
Recent Publications
1. Chikako SAOTOME “Investigation of Access to Research Materials in Life Science” Intellectual
Property Association of Japan, 2010.6
2. Hideho TANAKA, Kiyohide NAGAOKA, Katsuhiro INAMURA “Supply and Use of Intellectual
Capital in High-Tech Startups” Intellectual Property Association of Japan, 2010.6
3. Kiyohide NAGAOKA, Katsuhiro INAMURA, Hideho TANAKA “Supply and Use of Intellectual
Property by High-Tech Startups : Comparative Business Analysis” Intellectual Property
Association of Japan, 2010.6
4. Chikako Saotome, Hideho Tanaka “Management of Medical Intellectual Property and Publication
at Universities” Journal of Healthcare and Society, Vol.20, No.2, 155-167, 2010
- Public Health - Health Determinants
Health and Environmental Sciences
Our proximate goal is to analyze gene-environmental interactions for development of adverse health effects. As environmental
factors, persistent organic pollutants, nutrition and working conditions are within our research scope. Laboratory works, genetic
epidemiology and field studies are routinely used to solve the problems. Our long-term goal is to practice preventive measures
based on our findings. Candidates with public health mind, from any disciplines, will be welcome.
Akio Koizumi, M.D., Ph.D.
Professor
We are exposed to various health hazards. These
are found in routine life styles, diets, environmental
pollutants and occupational settings. To build
rational preventive measures, both susceptive genetic
determinants and environmental factors should be
taken into account. When our global environment
was clean, a phenotype susceptible to dioxins or to
formaldehyde had never emerged as a public health
issue. However, as our environment is contaminated
with chemicals, phenotypes associated with chemical
exposures have emerged as an important public
health issue: for example formaldehyde causes
asthma in some people while it does not in others.
In short, changes in environment always have
revealed new phenotypes and brought new public
health issues. We therefore consider it critical to
dissect gene-environmental interactions in a dynamic
state. On this basis, we would like to conduct public
health practices. Currently, following projects are
ongoing. The first one is to find susceptible genes
for Moyamoya disease (figures). We have also
analyzed in our laboratory from a viewpoint of
preventive medicine against brain infarction and
breeding in the childhood. In the second project, we
are assessing levels of exposure to persistent organic
pollutants in a 30-year span. In this project, we are
building the Environmental Sample Bank which is
open to the public. In parallel we are investigating
pharmacological actions of organofluorine
compounds at molecular levels. In the last project,
we are working on chronic kidney disease (CKD)
in Sri Lanka. In this project we are investigating the
mechanism and the prevention of CKD. We have still
other ongoing projects related to common diseases
such as diabetes.
Health and Environmental Scienices
Professor : Akio Koizumi
Associate
Professor : Kouji Harada
Lecturer
: Toshiaki Hitomi
Assistant
Professor : Kokoro Iwasawa
Research
Associate : Tamon Niisoe
JSPS Post Doctoral Fellow
: Hatasu Kobayashi
JSPS Post Docoral Fellow for Foreign Researcher
: Liu Wangyang
Researcher : Senevirathna Lalantha
TEL
: +81-75-753-4456
FAX
: +81-75-753-4458
e-mail
: [email protected]
[email protected].
kyoto-u.ac.jp
URL
: http://hes.med.kyoto-u.ac.jp/
❶
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❸
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❺
●
❷
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❹
●
❶ Our members
❷ Normal (left) and Moyamoya vessels
(right)
❸ Pedigrees of genetic analysis of
familial Moyamoya disease
❹ Atmospheric simulation of lead in
East Asia
❺ Field work of CKD in Sri Lanka
Recent Publications
1. Fujii Y et al., Detection of dicofol and related pesticides in human breast milk from China, Korea
and Japan. Chemosphere 2011, 82:25-31
2. Chandrajith R, Nanayakkara S et al., Chronic kidney diseases of uncertain etiology (CKDue)
in Sri Lanka: geographic distribution and environmental implications. Environ Geochem Health
2011:DOI: 10.1007/s10653-10010-19339-10651
3. Liu W et al., A rare Asian founder polymorphism of Raptor may explain the high prevalence of
Moyamoya disease among East Asians and its low prevalence among Caucasians. Environ Health
Prev Med 2010, 15:94-104
4. Hashikata H et al., Confirmation of an association of single-nucleotide polymorphism rs1333040
on 9p21 with familial and sporadic intracranial aneurysms in Japanese patients. Stroke 2010,
41:1138-1144
5. Niisoe T et al., Long-Term Simulation of Human Exposure to Atmospheric Perfluorooctanoic Acid
(PFOA) and Perfluorooctanoate (PFO) in the Osaka Urban Area, Japan. Environ Sci Technol 2010,
44:7852-7857
6. Inoue K et al., Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene
for intracranial aneurysm: a preliminary study. Circulation 2006, 113:2002-2010
Health Promotion and Human Behavior
Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public
Health, promotes pragmatic and empirical research on behaviors and cognitions that bear on disease and health of humankind.
Its two vehicles of research consist of cognitive-behavior therapy (CBT) and clinical epidemiology (evidence-based medicine:
EBM). CBT offers skills to produce changes in health-related behaviors and cognitions, while EBM provides solid methodology
to evaluate their effectiveness and to disseminate proven skills in the real world.
Toshiaki A. Furukawa, MD, PhD
Professor
The research themes in the Department currently
include:
1. In the field of CBT,
1.1. Research and development of new CBT
programs for anxiety disorders, mood disorders and
psychotic disorders
1.2. Research and development of CBT programs for
patients with physical diseases
1.3. Research and development of CBT programs
applicable to workplace and school
1.4. Research and development of methods to teach
and disseminate CBT
2. In the field of EBM,
2.1. Network meta-analyses of psychosocial and
biological therapies for depression (in collaboration
with the Cochrane Collaboration Depression,
Anxiety and Neurosis Group)
2.2. Research and development of new methods to
translate evidence into clinical practices, applying
epidemiology, statistics and psychometrics.
2.3. A pragmatic mega-trial to establish
optimum treatment strategies of new generation
antidepressants for major depression
We further plan to run the following workshops in the
near future.
3. Hands-On Workshop on How to Utilize EBM in
your Busy Clinic
4. Workshops on How to Complete Systematic
Reviews (Meta-analyses)
5. Introductory, Intermediate and Advanced
Workshops for CBT
The Department is also a collaborator for the Master
of Clinical Research program.
Recent Publications
1. Furukawa, T. A., McGuire, H., Barbui, C. (2002) Meta-analysis of effects and side-effects of low
For those who wish to study with us:
dosage tricyclic antidepressants for depression: systematic review. BMJ 325: 991-995.
We expect our MSc and PhD students to actively take 2. Geddes, J. R., Carney, S. M., Davies, C., Furukawa, T. A. et al (2003). Relapse prevention with
part in one of our on-going research projects.
antidepressant drug treatment in depressive disorders. Lancet 361: 653-661.
Health Promotion and Behavior Science
Professor : Toshiaki A. Furukawa, MD, PhD
Associate
Professor : Akiko Yamasaki, MD, PhD
TEL
: +81-75-753-9491
FAX
: +81-75-753-4641
e-mail
: [email protected]
URL
: http://ebmh.med.kyoto-u.ac.jp
Kyoto University
3. Otsu, A., Araki, S., Sakai, R. et al (2004) Effects of urbanization, economic development and
migration of workers on suicide mortality in Japan. Social Science & Medicine 58, 1137-1146.
4. Furukawa, T. A., Watanabe, N., Omori, I. M. et al (2007) Association between unreported
outcomes and effect size estimates in Cochrane meta-analyses. JAMA, 297, 468-470.
5. Cipriani, A., Furukawa, T. A., Salanti, G. et al (2009) Comparative efficacy and acceptability of 12
new-generation antidepressants: a multiple-treatments meta-analysis. Lancet, 373, 746-758.
Books
Furukawa, T. “Evidence-Based Psychiatry: From Theory to Practice” Igaku-Shoin, 2000.
Furukawa, T. “Cognitive-Behavior Therapy Live Sessions by A. T. Beck and J. Beck” Igaku-Shoin,
2008.
Furukawa, T. A., Jaeschke, R., Cook, D. Guyatt, G. (2008) Measurement of Patients' Experience. In
Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice (2nd edn),
pp. 249-271. New York: The McGraw-Hill Companies, Inc.
Preventive Services
Caring for the ill persons is the origin of medicine. Prevention of disease is another matter of importance. Prevention includes
preventing the occurrence of a disease (primary prevention) and arresting the progression of a disease through early diagnosis
and early treatment (secondary prevention). Kyoto University Health Service is the primary-care facility for preventive services,
such as health checkups and promotion, for students and employees of Kyoto University. We also provide health guidance and
counseling as well as primary care for diseases and injuries. In our practice, we conduct epidemiological research for disease
control and prevention, and develop various healthcare systems. In this way, we disseminate evidence from the on-site daily
clinical routine.
Takashi Kawamura, M.D., Ph.D.
Professor
“Sudden death of employees frequently occurs
in April and on weekends.” “Water-gargling
prevents common cold.” ”Chest compression-only
resuscitation is the best way for lay bystanders.”
“Introduction of hemodialysis in IgA nephropathy
can be predicted by blood pressure, urine protein,
❶ Randomized controlled
urine blood, serum albumin, etc.” ”Adverse events
t r i a l eva l u a t i n g t h e
of gefitinib are more common among patients
preventive effect of
with some characteristics.” We are studying quite
gargling for common
cold (Ref No.2)
common health problems to contribute to daily
❷
Patients cohort study
healthcare. Our study tool is epidemiology. We
identifying the risk
collaborate with many medical and governmental
fa c t o r s o f a d v e r s e
facilities all over the country.
events by gefitinib (Ref
In the School of Public Health, we participate in a
No.5)
core-course on “Epidemiology” which helps us to
evaluate the causes of a disease and the effectiveness
of medical procedures through observation and
intervention, and also in courses on ”Study protocol
writing and study management” and ”Cardinal points
in clinical research practice” for students who intend
to carry out clinical researches. We continuously
mentor each student assigned to our department. As a
graduate school student, some medical qualifications
are required because we study in practices. See the
webpage of the University Health Service.
Preventive Services
Professor : Takashi Kawamura
Associate
Professor : Kazumi Takemoto, Masahiko Ando
Senior
Lecturer : Masashi Goto
Assistant
Professor : Taku Iwami, Teruhisa Uwatoko
TEL
: +81-75-753-2400
FAX
: +81-75-753-2424
e-mail
: [email protected]
URL
: http://www.kyoto-u.ac.jp/health/kuhchome.html
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Recent Publications
1. Kawamura T, Kondo H, Hirai M, et al. Sudden death in the working population: a collaborative
study in central Japan. Eur Heart J 1999; 20: 338-343.
2. Satomura K, Kitamura T, Kawamura T, et al. Prevention of upper respiratory tract infections by
gargling: a randomized trial. Am J Prev Med 2005; 29: 302-307.
3. Iwami T, Kawamura T, Hiraide A, et al. Effectiveness of bystander-initiated cardiac-only
resuscitation for patients with out-of-hospital cardiac arrest. Circulation 2007; 116: 2900-2907.
4. Goto M, Kawamura T, Ando M, et al. A scoring system to predict renal outcome in IgA
nephropathy: a nationwide 10-year prospective cohort study. Nephrol Dial Transplant 2009; 24:
3068-3074.
5. Ando M, Okamoto I, Yamamoto N, et al. Predictive factors for interstitial lung disease, antitumor
response, and survival in non-small cell lung cancer patients treated with gefitinib. J Clin Oncol
2006; 24: 2549-2556.
- Public Health - International Health
Global Health and Socio-epidemiology
“Socio-epidemiology” is a new methodological approach for the New Public Health. Integrating sociological and
epidemiological perspectives and methodologies, it takes a multidisciplinary approach encompassing epidemiology,
biostatistics, mixed method, social marketing, behavioral science, and communication science. Utilizing this novel approach
while following the tradition of Kyoto University that appreciates field-based rather than “arm-chair” activities, we value the
practice in the field and contextual understanding of people, explore the solutions that are both scientific and socio-culturally
appropriate, and thus aim to contribute to the improvement of global health. With successful application of this approach to
the field of HIV/STDs epidemiology and prevention in Japan as well as abroad over the last decade, our department has been
designated as the first Collaborating Centre of the UNAIDS since 2006.
Masahiro Kihara, M.D., Ph.D.
Professor
❶
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Our major research projects include the WYSH Project
(Well-being of Youth in Social Happiness) in Japan and
the HADI Project (HIV/AIDS Prevention Studies among
Drug Users in Iran) in Iran. WYSH Project is an HIV/
STDs education project for youth, created through socioepidemiological approach in 2003. Having been proven
highly effective in improving knowledge, attitude and
behaviors, it has evolved into the largest project of its
kind in Japan and was adopted as a national project by
the Ministry of Education, Culture, Sports, Science and
Technology in 2007. The HADI Project has started in 2003
with a socio-epidemiological study that first described
the HIV epidemic among injecting drug users (IDUs) in
Iran and identified needle/syringe sharing practice during
incarceration as a major risk factor for HIV infection. Our
further studies showed the effectiveness of needle/syringe
exchange program in the community and the methadone
maintenance treatment in prison, having had a strong
impact on shaping the national HIV prevention programs
of Iran. Other research activities include HIV/STDs-related
behavior surveys in Japan as well as in many developing
countries including China, Thailand, Bangladesh, Nepal,
and Burkina Faso. Education and mentoring activities
Education activities are focused on the systematic
teaching of socio-epidemiology. In the first semester,
students learn the theoretical basis of socio-epidemiology;
how multiple methodologies and/or concepts including
quantitative method, qualitative method, behavioral
science, communication science, and social marketing,
are integrated to reach deep contextual understanding of
the people and to create effective and socio-culturally
appropriate prevention programs. In the second semester,
students will be given a series of lectures and practicum on
qualitative methods including focus group interviews, and
various types of qualitative data analysis and on the theories
and skills of questionnaire development. Throughout
this course students are expected to acquire enough
knowledge, skills and mindset to plan and implement
socio-epidemiological programs. Our department is
also responsible for the education of infectious disease
epidemiology, including the topics such as emerging and
re-emerging infectious diseases, mathematical modeling of
infectious disease epidemics, and field epidemiology.
Students of our department were/are from various countries
that include Iran, China, Zambia, Myanmar, Bangladesh,
Nepal, Peru, Democratic Republic of Congo, Thailand,
Swaziland and Yemen.
UNAIDS Collaborating Centre
Office of the UNAIDS Collaborating Centre for Socioepidemiological HIV Research is placed in our department.
Activities of the centre include research, training,
communication and networking.
Global Health and Socio-epidemiology
Professor : Masahiro Kihara, MD, PhD
Associate
Professor : Masako Ono-Kihara, Ph.D.
(Director of the UNAIDS
Collaborating Centre)
TEL
: +81-75-753-4350
FAX
: +81-75-753-4359
e-mail
: [email protected]
Kyoto University
❸
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❶ Opening ceremony for UNAIDS Collaborating Centre (2006, Kyoto) and the plate for the
centre
❷ Socio-epidemiological study on the risk behaviors of rickshaw pullers in Bangladesh
(2008)
❸ Socio-epidemiological studies on injecting drug users in Iran (2003 )
❹ National Training Course for the WYSH Project by MEXT (2009)
Recent Publications
1. Ono-Kihara M, Sato T, et al. Demographic and behavioral characteristics of non-sex worker
females attending sexually transmitted disease clinics in Japan: a nationwide case-control study.
BMC Public Health. (2010) 10:106
2. Zamani S, Ono-Kihara M, et al. Potential for sexual transmission of HIV infection from male
injecting-drug users who have sex with men in Tehran, Iran. Sex Transm Dis. 2010 [Epub ahead of
print]
3. Zamani S, Radfar R, et al. Prevalence of HIV/HCV/HBV infections and drug-related risk
behaviours amongst IDUs recruited through peer-driven sampling in Iran. Int J Drug Policy. 2010
[Epub ahead of print]
4. Zamani S, Farnia M, et al. Patterns of drug use and HIV-related risk behaviors among incarcerated
people in a prison in Iran. J Urban Health. 2010 Jul;87(4):603-16.
5. Zamani S, Farnia M, Tavakoli S, Gholizadeh M, Nazari M, Seddighi AA, Setayesh H, Afshar
P, Kihara M. A qualitative inquiry into methadone maintenance treatment for opioid-dependent
prisoners in Tehran, Iran. Int J Drug Policy. (2009) Apr 21. [Epub ahead of print]
6. Ma Q, Ono-Kihara M, Cong L, Xu G, Pan X, Zamani S, Ravari SM, Zhang D, Homma T, Kihara
M. Early initiation of sexual activity: a risk factor for sexually transmitted diseases, HIV infection,
and unwanted pregnancy among university students in China. BMC Public Health. (2009) Apr
22;9:111.PMID: 19383171
7. Hoque HE, Ono-Kihara M, Zamani S, Ravari SM, Kihara M. HIV-related risk behaviours and the
correlates among rickshaw pullers of Kamrangirchar, Dhaka, Bangladesh: a cross-sectional study
using probability sampling. BMC Public Health. (2009) Mar 11;9:80.PMID: 19284569
8. Homma T, Ono-Kihara M, Zamani S, Nishimura YH, Kobori E, Hidaka Y, Ravari SM, Kihara M.
Demographic and behavioral characteristics of male sexually transmitted disease patients in Japan:
A nationwide case-control study. Sex Transm Dis (2008) Oct 2. [Epub ahead of print]
- Public Health - International Health
Public Health and International Health
Japan has attained the high life expectancy and low infant death rate which we can be proud of. Based on a historical viewpoint,
we study the public health and the health policy of Japan supporting this life expectancy and healthy life style, and are targeting
to contribute to the development of a future healthy policy. We also carry out research on the global health policy by WHO etc.
The basic knowledge of the public health is necessary for the further study on Japanese health policy. For such reasons, we would
like researchers with enough knowledge on general medicine and/or the public health system of the country and fluent English
speaking faculty.
Toshitaka Nakahara, M.D., PH.D., M.P.H.
Professor
Our department is the Public Health in Faculty of
Medicine and the Public Health and International
Health in the School of Public Health. In education,
we are carrying out several programs, such as the
“public health” lectures in the Faculty of Medicine
and the School of Health Science, “community
nursing” in the School of Health Science and corecurriculum, “health policy” and “international
health” in the School of Public Health. Being
based on a historical viewpoint of healthy political
science and by using the qualitative and quantitative
analysis method and/or its fusion-technique, and
the social-marketing-technique, we investigate
the current situation and the most effective health
policies. The tobacco control measures are important
subjects not only in Japan but also in the global,
and we are advancing these topics positively. We
also give lectures at conferences in abroad on the
preventable smoking measures. In the field of
international health, we collect the information on the
international systems including WHO, and compare
them with those of Japan etc. Now, besides the
research on health policies of Japan, we study laws
and regulations regarding public health. Also, we
study and compare food safety measures including
measures, against terrorism in Japan and foreign
countries.
❶
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❷
●
❶ The 7th Annual Meeting of International Society for the Prevention of Tobacco Induced
Diseases
❷ Staff
Recent Publications
Public Health and International Health
Professor : Toshitaka Nakahara
Associate
Professor : Kazunari Satomura
Assistant
Professor : Suketaka Iwanaga
TEL
: +81-75-753-4465
FAX
: +81-75-753-4466
e-mail
: [email protected]
1. Current Japanese Tobbacco Consumption Situation. Toshitaka Nakahara, K. Satomura, S.
Iwanaga, R. Sakamoto, M. Noami, T. Takahashi Tobacco Counters Health, Volume 4, ISBN 817211-208-4, P.11-13 2005
2. Hospital's Measures against Passive Smoking. Ryota Sakamoto, Toshitaka Nakahara, Kazunari
Satomura, Suketaka Iwanaga, Megumi Noami, Akihiko Kinugasa Tobacco Counters Health,
Volume 4, ISBN 81-7211-208-4, P.23-27 2005
3. What is Necessary to Obey the FCTC in Japan. Kazunari Satomura, Toshitaka Nakahara, Suketaka
Iwanaga, Ryota Sakamoto, Megumi Noami, Toru Takahashi Tobacco Counters Health, Volume 4,
ISBN 81-7211-208-4, P.32-35 2005
4. Changes of Health Warning Labellings on Japanese Tobacco Packages Suketaka Iwanaga,
Toshitaka Nakahara, Kazunari Satomura, Ryota Sakamoto, Megumi Nomai, Toru Takahashi
Tobacco Counters Health, Volume 4, ISBN 81-7211-208-4, P.36-38 2005
5. New approaches to public health education, research and practice Toshitaka Nakahara, Raku-Yu 10
4-5 2006
6. Takashi Muto, Toshitaka Nakahara, Eun Woo Nam : Asian Perspectives and Evidence on Health
Promotion and Education. Springer 2011
- Public Health - Center for Southeast Asian Studies
Division of Integrated Area Studies
Of the risk factors that are distributed in the environment and influence human health pathogenic microorganisms are important.
Various factors affect the process where pathogenic microorganisms in the environment cause infections. The factors in the
natural environment influence the survival and propagation of pathogenic microorganisms. Socioeconomic factors in the humanlife environment have effects on the contact between pathogens and humans, resistance of individuals as well as the community,
and so on and thus greatly affect the emergence of infectious diseases. In addition, these factors may influence each other. We
analyze how various factors interact with individual pathogen and the infection using an ecological approach.
Mitsuaki Nishibuchi, Ph.D.
Professor
We try to guide graduate students so that they can
learn the approach for comprehensive analysis of
various factors including the natural environment
where pathogens persist, the human environment,
the resistance of humans as the host of pathogens in
order to understand emergence and transmission of
infectious diseases.
We carry out studies in Thailand, Malaysia,
Vi e t n a m , I n d i a , B a n g l a d e s h , a n d C h i n a i n
collaboration with local researchers. We isolate
Vibrio cholerae, Vibrio parahaemolyticus, and
Escherichia coli O157 from the environmental
and clinical specimens and analyze the isolated
strains. We investigate the factors affecting the
emergence of infectious diseases by comparative and
comprehensive analysis of the isolated bacteria and
the environmental and clinical data.
We also study the infectious diseases that are not
restricted to a country or an area but are spread across
international borders. We determine and compare
the phenotypic and genetic characters of the strains
isolated in various areas to clarify their phylogenetic
relationships to understand the epidemiology of
infectious diseases. Investigation of the relationship
between the phylogenetic relationship of the
strains and international movement of humans and
commodities will allow us to reveal the factors
involved in transmission of infectious diseases.
For example, contamination of food materials by
the pathogens in the natural environment becomes
a risk factor for local people as well as the threat
to the people in other parts of the world. However,
incidence of infections may differ considerably
from area to area. If we include analysis of these
observations, the study starting at a “micro” level can
be expanded to cover the investigation of infectious
diseases at a “macro” level.
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❶ Environmental survey to assess
the risk of Vibrio parahaemolyticus
in bloody clams in Thailand
❷ Inter view to examine the
relationship between the incidence
of diarrhea and socioeconomic
factors in Vietnam
❸ We developed a quick and easy
genetic method to identify the
new clone of V. parahaemolyticus
responsible for pandemic spread
of infection. This method has been
used by many workers in various
parts of the world
❹
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Recent Publications
Professor : Mitsuaki Nishibuchi
TEL
: +81-75-753-4442
FAX
: +81-75-753-7350
e-mail
: [email protected]
URL
: http://www.cseas.kyoto-u.ac.jp/index_
ja.htm
Kyoto University
1. Nakaguchi, Y., and M. Nishibuchi. 2005. The promoter region rather than its downstream inverted
repeat sequence is responsible for low-level transcription of the thermostable direct hemolysinrelated hemolysin (trh) gene of Vibrio parahaemolyticus. J. Bacteriol. 187(5):1849-1855.
2. Koitabashi, T., V. Vuddhakul, S. Radu, T. Morigaki, N. Asai, Y. Nakaguchi, and M. Nishibuchi.
2006. Genetic characterization of Escherichia coli O157:H7/- strains carrying the stx2 gene but not
producing Shiga toxin 2. Microbiol. Immunol. 50(2): 135-148.
3. Koitabashi, T., S. Cui, K. Muhammad, and M. Nishibuchi. 2008. Isolation and characterization
of the Shiga toxin gene (stx)-bearing Escherichia coli O157 and non-O157 from retail meats in
Shandong Province, China and characterization of the O157-derived stx2 phages. J. Food Prot.
71(4):706-713.
- Public Health - Field Medicine - Center for Southeast Asian Studies
Field Medicine
Division of Humans' and the Environment
Modern clinical (bed-side) medicine have much succeeded in the lifesaving of the patients with acute diseases. As the results
now, aging population have developed not only developed countries but also developing countries. However, modern clinical
medicine in the hospital cannot completely deal with community-dwelling frail elderly patients with several chronic conditions
living in each different ecology and socio-economical situation. Field medicine is addressing the comprehensive geriatric issues
of community-dwelling elderly in the world using comprehensive geriatric assessment through actual medical field works.
Kozo Matsubayashi, M.D., Ph.D.
Professor
Working issues of our field medical teams are below.
❶
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(1) Comprehensive geriatric assessment and
community-based intervention for the communitydwelling elderly in Japan.
Comprehensive geriatric assessment and
community-based intervention for the communitydwelling elderly have been carried out in Kahoku and
Tosa in Kochi, Sonobe in Kyoto, Yogo in Shiga and
Urausu in Hokkaido.
(2) Comprehensive geriatric assessment for the
community-dwelling elderly in Asia.
Cross-sectional comprehensive geriatric assessment
for the community-dwelling elderly have been
carried out in Korea, West Java in Indonesia,
Vietnam, Laos and Myanmar.
❷
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(3) Medical research for nerurodegenerative diseases
in West Papua.
We have carried out medical field research
for amyotrophic lateral sclerosis and
Parkinson·Demantia complex disease in West Papua
(Irianjaya) in Indonesia detecting some above
patients. Future study is needed for etiological
assessment.
❶ A scene of CGA in West Java in Indonesia.
❷ Home visit patients living in a house on the tree, in West Papua.
Recent Publications
Field Medicine
Professor : Kozo Matsubayashi
TEL
: +81-75-753-7368
FAX
: +81-75-753-7168
e-mail
: [email protected]
URL
1. Matsubayashi K et al. Mood Disorders in the Community-Dwelling Elderly in Asia. J Am Geriatr
Soc, 58 (1);213-214, 2010.
2. Matsubayashi K et al. ,Changing attitudes of elderly Japanese toward disease. J Am Geriatr Soc.
57 (9), 1732-1733, 2009.
3. Kimura Y et al. Comprehensive geriatric assessment of elderly highlanders in Qinghai, China IV:
Comparison of food diversity and its relation to health of Han and Tibetan elderly. Geriatr Gerontol
Int 9 (4):359-365, 2009.
4. Okumiya K et al. Improvement in obesity and glucose tolerance in elderly people after lifestyle
exchange 1 year after an oral glucose tolenrance test in a rural area in LAO People’s Democratic
Republic. J Am Geriatr Soc 56: 1582-1583, 2008.
5. Fujisawa M et al. Trends in diabetes. Lancet 369:1257, 2007
- Basic Nursing Science
The environment is the theme that has been taken up since the time of Nightingale, and is placed as one of the basic concept
in nursing science. The environment has various influences on the health of people, but the recognition and relation for the
environment have changed according to the state of mental and physical health. Conventionally, the relations between the person
and the environment have been discussed in terms of determinism or the interaction theory. However, "Man-Environment
System" has become widely accepted.
In our field, we investigate the healthy phenomena in various fields scientifically from the viewpoint of "Man -Environment
System" with the aim of building a new domain called the environmental health nursing.
Sawako Suga, C.C.P., Ph.D.
Professor
The main studies of our stuff are as follows; 1.study
of the relationship between living environment
and sleep-wake rhythm of home care patients,
2.study about the influence of light environment
gives to sleep-wake cycle, and 3.study about the
technique of moving and positioning the patient in
bed. In addition, 4.study of the nursing counseling,
sandplay-drama method story method and mental
health of school or the workplace that we store on
verbal and nonverbal communication.
For study environment, a living environment
system laboratory and an interview / developmental
assessment room are prepared. In the living
environment system laboratory, we can make several
study that we experiment of daily life of home care
patients or controlled the environmental parameter.
In addition, we can enforce counseling, interview and
sand play technique in an interview / developmental
assessment room.
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❶ Actgram and sleep-wake analysis of home care patient with Actiwatch
❷ Influences of different light intensities during daytime
❸ Pressure mapping in tilt position
❹ One scene of sandplay-drama method
Professor : Sawako Suga, C.C.P., Ph.D.
Associate
Professor : Tomoko Wakamura, R.N., P.H.N., Ph.D.
Assistant
Professor : Kazuyo Suzuki, R.N., P.H.N., M.A.
List for Tel, Fax &E-Mail
: See page 000-000
Kyoto University
Recent Publications
1. Suga S, Miyajima A, Wakamura T, Suzuki K :Communication in Nursing Care. Igakugeijutsusha,
2009
2. Suga S : Psychology concerning nurse’s interpersonal relationship, Medica,2007
3. Wakamura T: Biological Rhythm and Health Science, Maruzen, 2008
4. Suzuki K, Miyajima A: The trial of nursing education to bring up the health outlook. Annual
Reports of Human Health Sciences Graduate School of Medicine, Kyoto University, 5; 37-41,2008
5. Kubota Y, Takasu NN, Horita S, Kondo M, Shimizu M, Okada T, Wakamura T, Toichi M.,
Dorsolateral prefrontal cortical oxygenation during REM sleep in humans. Brain Res. 2011 Mar 4.
- Nursing Science - Basic Nursing Science
Human Body Defense & Patho-physiology
Nursing Science
Homeostasis has evolved over time as an internal mechanism to protect the body against harmful pathogens such as bacteria and
many kinds of physical, chemical and social stressors. Defense functions are one component of homeostasis in living creatures.
Human Body Defense and Patho-physiology Nursing Science aims to introduce and discuss (i) infection as one source of body
immune reaction, (ii) hospital acquired infection, (iii) mechanisms of body defense and (iv) epidemiology. It also focuses on life
factors such as stress which effect reduction of or activation of body defense functions. This course‘s final aim is to establish
the new theories for prevention of infection and infection control for immuno-compromised hosts based on a holistic human
approach through clinical and laboratory study.
Yumi Saito
Shinichi Nomoto
Research
The focus of clinical study in this course particularly
concerns infection prevention for immunocompromised patients, and their quality of life.
Continuous study in the laboratory setting elucidate
causative factors of reactivation of infection
for the compromised host and the mechanisms
of reactivation. The theme of applied studies is
development of nursing care for infection prevention
in compromised patients by improving their state of
stress and their immune function.
Education
Education for undergraduates deals with the
concept of Host-Environment Interaction, basic
theories of hospital infection control and basic
knowledge of immune function. It also covers
teaching for laboratory techniques for investigation
and identification of bacterial pathogens and blood
tests for identifying antibodies as an introduction of
Human Body Defense and Patho-physiology Nursing
Science.
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❶ Figure 1: Show the results of mean change of biochemical stress parameter, cortisol and
chromogranin A after viewing color images. The participants are 20 healthy worker (study
group:10 persons, control group:10 persons)
❷ Table 1: Show the results of mean change of biochemical stress parameter, cortisol and
chromogranin A and the change of multiple mood score after viewing color images.
Recent Publications
Human Body Defense & Patho-physiology
Nursing Science
Professor : Yumi Saito, RN, MNS, PhD.
Shinichi Nomoto, MD, D.Med.Sc.
Assistant
Professor : Momoe Utsumi
List for Tel, Fax& E-Mail
: See page 000-000
1. Effectiveness of preferabole color light on psychosomatic state evaluated by emotional parameter
and biochemical parameters. Yumi SAITO, Etsu RA, Satoshi SASAYAMA, Kuniaki SAITO,
Hiroki TOYOKAWA
2. Yumi Saito,Satoshi Sasayama, Sawako Suga,Masaki Ikemoto: Effects of Color Images on
Psychosomatic State- Effectiveness of Color Images as Mood Stimulants as Assessed by Using an
Image Selection System- . Japanese Journal of Complementary and Alternative Medicine Vol.5,
p225-232, 2008
3. Yumi Saito, Harue Tada: Effects of color images on stress reduction: Using images as mood
stimulants. JANS 4, 1-8, 2007
4. Yumi Saito, Sawako Suga: The Study of the Effectiveness of Color Images on Stress Reduction
Health Science 2: 1-7, 2006.( School of Health Sciences, Faculty of Medicine , Kyoto University).
5. Yumi Saito,Keiko Seki,Tomoko Ohara,Chieko Shimauchi,Yoko Honma, Mutsumu Hayashi,Shogo
Masuda,Masayasu Nakano: Epidemiologic Typing of Methicillin-Resistant Staphylococcus aureus
in Neonate Intensive Care Unite Using Pulsed-Field Gel Electrophoresis. MICROBIOLOGY and
IMMUNOLOGY 42 (11) 1998
- Nursing Science - Clinical Nursing Science
Nursing Science for Lifestyle-Related Diseases
As health and social lifestyles have been changing in recent years, lifestyle-related diseases have been increasing, even among
younger people, posing important social problems. In this course, you will learn nursing intervention to prevent lifestyle-related
diseases and their associated complications. You are expected to obtain knowledge about nursing care/treatment to help patients
modify their behavior as well as nursing theories, and thus develop practical skills. You are also expected to cultivate your
abilities to improve clinical practices and nursing education, and to review them based on scientific evidence.
Kiminori Hosoda MD. Ph.D
Kazuko Nin RN. Ph.D
Professor
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Our research team is engaged in developing “nursing
diagnostic indicators,” “nursing intervention
techniques,” and “outcome indicators” for patients
with chronic disorders. Specifically, for patients with
diabetes to be protected from the development or
advancement of complications, we are conducting
research on: 1) self-care behavior, 2) nursing
diagnosis/intervention for foot care and evaluation
of the intervention, and 3) risks for developing foot
ulcer in patients with diabetes. For patients with
postoperative lymphedema such as those following
an operation for uterine cancer, we are undertaking
research on 4) nursing diagnosis/intervention for
lymphatic drainage. For patients with respiratory or
neuromuscular disorders, we are studying 5) nursing
diagnosis/intervention for lung physiotherapy
(squeezing).
Regarding educational activities, we are committed ●
❷
to cultivating the ability to comprehensively
understand patients in different stages including the
onset of lifestyle-related diseases and their remission,
exacerbation, and acute exacerbation. We are also
engaged in developing the assessment capability
to solve nursing problems in patients with chronic
disorders, as well as nursing intervention techniques
and the ability to evaluate the intervention. For
these purposes, training contents are focused on
understanding peripheral theories for nursing
diagnosis, acquiring nursing intervention techniques,
and analyzing the results. Instructors for our team are
working for the outpatient departments at the Kyoto ❶ This is our experimental setup.
University Hospital. Exploiting these advantages ❷ We developed a foot simulator.
to the full, we provide a curriculum incorporating
seminars and practices as well as lectures, thus
aiming to nurture competitive clinical nurses and
teachers equipped with superior nursing intervention
techniques.
Recent Publications
Nursing Science for Lifestyle-Related
Diseases
Professor : Kiminori Hosoda, Kazuko Nin
Associate
Professor : Ikumi Honda, Hiromi Sakuda
List for Tel, Fax & E-Mail
: See page 000-000
Kyoto University
1. Sumikawa MD, Egawa T, Honda I, Yamamoto Y, Sumikawa Y, Kubota M (2007) Effects of foot
care intervention including nail drilling combined with topical antifungal application in diabetic
patients with onychomycosis. The Journal of Dermatology, 34, 456-464
2. Daitoku M, Egawa T, Fujiwara Y, Okumiya A(2007) Effects of foot care intervention on self-care
behavior in the patients with diabetes mellitus. Journal of the Japan Diabetes Society 50(2) p 163172
3. T. Tanaka, H. Masuzaki, S. Yasue, K. Ebihara, T. Shiuchi, T. Ishii, N. Arai, M. Hirata, H.
Yamamoto, T. Hayashi, K. Hosoda, Y. Minokoshi, K. Nakao. Central Melanocortin Signaling
Restores Skeletal Muscle AMP-Activated Protein Kinase Phosphorylation in Mice Fed a High-Fat
Diet. Cell Metab. 5(5):395-402, 2007
You will learn nursing science for critical care and advanced medical treatment to acquire specialized knowledge and nursing
skills that prepare you for sophisticated medical technologies involving considerably invasive procedures such as transplantation
and heart, lung, and brain surgery, and to develop a nursing assessment capability, an ability to make clinical decisions in
nursing, and practical nursing skills. From the viewpoint of holistic medicine, we guide you in utilizing knowledge based on
nursing theories as well as various principles and findings in closely-related disciplines for the sake of patients and their families
facing life-threatening or daily stressful situations
In highly-advanced medicine, specifically in
transplantation and regenerative medicine invasive
both physically and mentally, nursing practice is
essential in each of the first-aid, perioperative,
critical, recovery, and self-management stages. In
this course of nursing science for critical care, with a
special focus on the first-aid, perioperative, critical,
and recovery stages, we instruct you to explore
nursing care and establish nursing models not only
for patients under life-threatening conditions but for
living donors (in the case of organ transplantation)
and for the families concerned. The curriculum is
designed in view of advanced medicine-related social
policies, care systems, and ethical challenges.
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❶ The Relationship Between
Postoperative Psychiatric
Disorders (PPDs) and
Psychosocial Factors in
Adult Living-Related Liver
Tr a n s p l a n t a t i o n ( L R LT )
Recipients
❷ The Relationship Between
Postoperative Psychiatric
Disorders (PPDs) and
Recover y Process of
Adult Living-Related Liver
Tr a n s p l a n t a t i o n ( L R LT )
Recipients
❸ Developing the Ability of
the Self-Directed Learning
through the IBL Learning
Method in Adult Health
Nursing Education
Recent Publications
Associate
Professor : Chiharu Akazawa
Teaching
Associate : Risa Fukuda
: See page 000-000
1. Chiharu Akazawa, Ayako Okutsu, Sayoko Teraguchi et al; The Relationship Between
Postoperative Psychiatric Disorders(PPDs) and Psychosocial Factors in Adult Living-Related Liver
Transplantation (LRLT) Recipients; ITNS ,2006.
2. Ayako Okutsu, Chiharu Akazawa, Sayoko Teraguchi et al; The Relationship Between
Postoperative Psychiatric Disorders(PPDs) and Recovery Process of Adult Living-Related Liver
Transplantation(LRLT) Recipients ; ITNS ,2006.
3. Teiko NISHIZONO, Chiharu AKAZAWA,Yuko HAYASHI, Masako MIYATA,Masae
YAMAMOTO;Developing the Ability of the Self-Directed Learning through the IBL Learning
Method in Adult Health Nursing Education; International Nurse Educators Conference,2007.
4. Chiharu Akazawa, Sayoko Teraguchi, Teiko Nishizono:Postoperative psychiatric symptoms(PPS)
adult living-related liver transplantation(LRLT) in Japan:What are the physical and psychological
factor?,JapanAcademy of Transplantation and Regeneration nursing,4(2),P1-10,2009.
5. Okamoto S, Slingsby BT, Nakayama T, Nakamura K, Fukuda R et al; Barriers to vaccination
among Japanese medical students: focus group interviews. Pediatr Int. 2008; 50(3): 300-5.
Psychiatric Nursing
There are 10 million emails sent in the world each day, 80-90% of which are said to be spam. Even in such advanced information
societies, human behavior remains frivolous. This kind of human behavior cannot be unraveled with higher brain functions
only. We must also consider the huge impacts on the human mind of cultures, their histories, individual life histories, and social
environments. In the light of this background, psychiatric nursing will clarify the mechanisms of the mind that produce barriers
in human relations, developmental problems, and the difficulty of living to achieve self-realization. Our major research theme is
support that enables better mental activities and social living by means of conducting joint trials.
Shigeru Sakuraba
Professor
We are in charge of psychiatric nursing for mental
care targeting mental problems in a wide range of
human health science. In education in the graduate
school we are in charge of medical psychology,
psychiatric nursing theory, clinical practice and
practicums. The practicums in the graduate school
are essential credits to acquire a license as a clinical
psychiatric nurse specialist. In addition, “Health
Psychology,” which is a course common to all
departments, is taught by Suga, Toichi, and Sakuraba,
and the textbook has been released as a single volume
in the “Kyoto University Popular Lecture Series”.
In addition to the mental diseases of psychiatry, our
research examines phenomena that reflect modern
society such as depression, suicide, bullying, social
withdrawal, and abuse. Sakuraba and Konishi use
their clinical experience to conduct surveys and
analysis of care of the many people with mental
difficulties and ways of dealing with them, and
support to help connect them to social life from the
perspectives of nursing. We have conducted many
studies on effective assistance methods. Suicide
research in people with alcohol dependence was also
conducted, part of which was picked up as news by
the American Psychiatric Association. There is also
a focus on psychiatric care of transplant patients
in liaison psychiatric nursing, and qualitative and
quantitative studies are conducted. Study results
have been published by the American Society for
Artificial Internal Organs. We have visited of the
German Berlin Cardiac Disease Center (Deutsches
Herzzentrum Berlin), and actively pursue organ
transplant surveys and studies in other countries.
Konishi,nursing effect caught affection change of
man as the attempt to consider the effect from brain
activity using brain wave or NIRS (near-infrared
spectroscopy). The subjects of our studies range from
toddlers to the aged of both sexes. In other words,
mental problems of people from birth to death are
approached from various perspectives, and mental
issues in all social settings are studied. Surveys
and research with research institutions in various
countries are conducted on organ transplants with
respect to psychiatric support and team medicine,
which is essential to advanced medical care. Our aim
is to train medical personnel who can aid various
people mentally.
Psychiatric Nursing
Professor : Shigeru Sakuraba
Assistant
Professor : Nami Konishi
: See page 000-000
Kyoto University
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❶ The church of the Ger man
Berlin Cardiac Disease Center
(Deutsches Herzzentrum Berlin)
❷ staffs
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Recent Publications
1. D.Milne, Sakuraba Shigeru, Matushita Masaaki. Japan Gapples with Alcoholism Crisis.
Psychiatric News (APA) 38 (23),2003.
2. Sakuraba Shigeru, Kubo Masako, Komoda Takeshi, Yamana Junichi. Suicidal Ideation and
Alexithymia in Patients with Alcoholism: A Pilot Study. Substance Use & Misuse, 40: 823-830,
2005
3. Komoda Takeshi, Drews Thorsten, Sakuraba Shigeru, Kubo Masako, Hetzer Roland. Executive
Cognitive Dysfunction without Stroke after Long-Term Mechanical Circulatory Support, American
Society for Artificial Internal Organs Journal, 51(6): 764-768, 2005
4. Sakuraba Shigeru, Suzuki Mayo, Tatemori Hisateru, Saito Mari, Kurita Hiroshi.Screening Scale
for Pervasive Developmental Disorder : Using Tokyo Child Development Schedule and Tokyo
Autistic Behavior Scales.Books of Abstracts of XIXth World Congress of World Association for
Social Psychiatry:124,2007.
5. Suzuki Mayo,Sakuraba Shigeru.Coparisom of self-efficscy for social participation between
competitively and non-competitively employed consumers with psychiatric disabilities.10th
International Congress of Behavioral Medicine Abstract book,244,2008.
6. Suzuki Mayo, Sakuraba Shigeru. The internal world of patients with major depressive disorder.
10th International Congress of Behavioral Medicine. 2008. 8 Tokyo.
7. Sakuraba Shigeru.Eating disorders care in child and Adolescence.13th Japan Eating disorder
Association,12,2009.
- Nursing Science - Family Nursing Science
Child Health and Development Nursing
We focus on nursing of medically dependent children and their families in terms of teaching professional knowledge and care
techniques and developing nursing assessment and nursing practice abilities in order to understand the growth/development and
living environments of children in the context of the falling birthrate, and help such children and their families maintain and
improve their health for life. We aim to develop child/family-aiding strategies based on nursing trends in child/family-oriented
theories and literature, and on the roles of child health and development nursing specialists in collaboration with related areas
such as sociology, healthcare, welfare, and education.
Machiko Suzuki RN, PHN, PhD
Professor
For children and their families to maintain and
improve their health for life, it is important to
practice nursing that targets diseases in adults,
who nurture the next generation after completing
their own developmental course. Thus, we provide
research guidance focused on the following:
1) Development of self-help (then independence)
measures for disabled children with refractory
diseases, long-term hospitalized children highly
dependent on medical support such as mechanical
ventilation, and home-care children living in the
community, as well as childrearing support for their
families;
2) development of network models to support abused
children and families facing child abuse/death;
3) identification of ideal collaboration with various
specialists in school education (for both normal
and disabled children) and clarification of the
professional functions and roles of nurses; and
4) development of nursing-care methods for children
with cancer.
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❶ Suzuki (the second from the
right) visited a 42-year-old male
patient with muscular dystrophy
who had been home-cared on
24-hour mechanical ventilation
for 19 years in NJ, USA, with
Dr. Bach, a world authority on
NIPPV, and his co-researchers to
seek measures to promote selfhelp.
❷ Lecture meeting
“Hiromi looked ver y pleased
with the mini-live, smiling all the
time. Although I was sorry for Dr.
Hatakeyama, I could not help
laughing because there was a
considerable difference between
his lecture and attitude. His talk
about ‘prior reading’ was very
suggestive. With no apparent
tiredness, Hiromi is now taking a
lesson using the switch. We look
forward to another opportunity to
meet challengers and let them
refresh our minds and energize
us.”In a community-support event
held since 2000 in Hiroshima
Prefecture for home-care
children/adults highly dependent
on medical suppor t such as
mechanical ventilation
❸ Home-care child support system
model (draft), developed based
on community support activities
Development of home-care child
support systems
College teaching staff-unique
contribution to the community
Activities by the review board:
lecture meeting, training session,
exchange
meeting,case-study meeting, and
direct support
Provision of oppor tunities to
review and reconfirm knowledge/
techniques, formation of new
networks, empowerment, window
service to directly suppor t
individuals.
Recent Publications
Child Health and Development Nursing
Professor : Machiko Suzuki
Assistant
Professor : Kanako Kiyokawa
: See page 000-000
URL
: http://www.hs.med.kyoto-u.ac.jp/
childcare/
1. Machiko Suzuki (March 2007): Ideal support for self-help in home-care children on mechanical
ventilation -- a review of actual conditions in Chugoku and Shikoku areas and a model case in New
Jersey; Child Health Research, 66(2), 315-321.
2. Machiko Suzuki (July 2006): The current status of pediatric rehabilitation in foreign countries;
Pediatric Nursing, 29(8), 1137-1140.
3. Machiko Suzuki (2006): Seeking ideal home-visit nursing to support home care; Home-Visit
Nursing and Nursing Care, 11(2), 139-148.
4. Machiko Suzuki (2006): Building home-care support systems for children under prolonged
treatment; Nursing Education, 47(5), 389-393.
5. Machiko Suzuki (2004): A home-care support system model for children in extremely severe
conditions -- 1st report: activities and results by the “review board” in the whole community; Child
Health Research, 63(5), 583-589.
- Nursing Science - Family Nursing Science
Midwifery & Women’s Health
The social environment within which Japanese women live has undergone remarkable change in recent years. Obstetrics in
Japan is currently faced with many problems, including a falling birth rate, a shortage of obstetricians, fewer childbirth facilities,
increasing numbers of infertile couples, and child abuse. These problems have arisen due to a variety of factors, including the
advent of the nuclear family. The Health and Welfare Ministry has recently reinforced its strategy of support for childbearing,
which aims to ensure enjoyable childbirth and childbearing in society. In this context, midwives are responsible for the care of
mothers and children as their healthcare provider. As a student in this course, you will have completed advanced education with
a focus on the primary healthcare needs of women throughout their entire life-cycle and will have experience as a specialist
midwife and maternal and child-healthcare provider as an autonomous practitioner. Students will be expected to be able to
educate midwives in theoretical knowledge and be skilled in the role of lead professional.
In the midwifery field, you will undertake
programs specially designed to develop and achieve
competencies, theory, skills, and knowledge as an
autonomous practitioner attending to mothers during
antenatal, intranatal, and postnatal periods and with
the neonate and child. You will also ensure that
students have the ability to recognize and diagnosis
potential problems and complications in high-risk
pregnant women and children.
In the field of women’s health, you will undertake
programs concerned with the primary healthcare
needs of women throughout their life-cycle, as well
as how to support couples undergoing infertility
treatment. This course is designed to provide
students with the theoretical and practical knowledge
and skills necessary to practice midwifery in a
multidisciplinary context by EBN. Students will
undertake independent research on a topic of interest
and develop their critical, conceptual, and analytical
skills, applying relevant research techniques to
their chosen field of study. The program, titled
“Emotional and Physical Counseling for Women,”
is a collaborative venture with Kyoto University
Hospital developed to promote health services and
improve clinical skills.
Professor
❶ P r o f. K . K a b e y a m a
(middle of the bottom)
with staffs of Karalinska
Institute, Stockholm
❷ Ultrasound scan in the
midwifery diagnosis
❸ Measurement of the
a u t o n o m i c n e r vo u s
functions
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Kiyoko Kabeyama
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Research topics currently covered in related family
nursing include reproductive health, infertility
treatment, development of perinatal management
systems, women’s smoking status, and maternal
nutritional management. Faculty members are
currently conducting research into the promotion of
health services, not only nationally but also in an
international context, especially in underdeveloped
countries from a global perspective.
Recent Publications
Midwifery & Women’s Health
Professor : Kiyoko Kabeyama
Associate
Professor : Keiko Yagi
Senior
Lecturer : Midori Kanaoka
Assistant
Professor : Yoko Chiba
: See page 000-000
Kyoto University
1. Kabeyama K. et al. Textbook for Midwives 1~8, Igaku-Shoin, Tokyo, 2008
2. Kabeyama K. et al. Physical Examination for Midwives, Igaku-Shoin, Tokyo, 2008
3. Watanabe H. Kabeyama K. et al. A Review of Inadequate and Excessive Weight Gain in Pregnancy,
Bentham Science, 5(4), 186-192, 2009
4. Kabeyama K. Longitudinal study of the intensity of memorized labour pain, International J of
Nursing Practice, 7, 56-63, 2001
5. Chiba Y, et al. Gaps between maternity service and record-keeping in the two district hospitals in
Western Kenya. 28th Triennial Congress of International Confederation of Midwives (ICM), 2008
6. Chiba Y, Yamaguchi K, Kabeyama K. Differences between Japanese programs in acquiring
midwifery skills through practicum: Comparison of self-evaluations and instructor evaluations on
student achievement. International Conference of International Confederation of Nurses (ICN),
2007
7. Gesso A. Kabeyama K. An analysis of the multipara’s concerns at the last term of pregnancy, ICN
23rd Quadrennial Congress, 302, 2005
- Nursing Science - Community Health and Community Health Nursing
Preventive Nursing
Prevention is the origin of, as well as a fundamental component of community health nursing. Throughout the life cycle, from
infancy to old age, preventive activities in a variety of fields of community health care are indispensable for a life of high quality.
So we welcome public health nurses and health care professionals who wish to learn the methods to elucidate health promoting
factors or health deteriorating factors, such as lifestyle or socio-cultural background. The program includes evidence-based
preventive activities and health care, and networks and systems for preventive activities, the framing policy for the purpose of
building a healthy community and promoting health of community residents.
Toshiki Katsura , R.P.H.N. , R.N. , Ph.D.
Professor
We aim to train public health nurses and other
health care professionals in promoting independent
preventive activities and research contributing to
building of healthy communities. Objectives include
successful aging and health promotion of community
residents using epidemiological methods or other
scientific methods, both quantitative and qualitative,
which are currently employed in health care and
health promotion activities.
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Current projects include:
1) Epidemiological studies in community and work
populations for prevention of cardiovascular diseases
or metabolic syndrome, and plan-do-see preventive
approaches to lifestyle modification and weight
management for overweight residents with metabolic
syndrome.
2) Field studies on prevention of bed-boundedness
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and house-boundedness aiming at successful aging
in the very elderly or elderly living alone. We are
involved in joint field studies and experimental
studies, such as sight information processing and
risk cognition in the elderly, including elucidation of
mechanisms of falls and fall prevention.
❶ Characteristics in the fixation point and the visual search of an elderly faller in comparison
3) We have developed a residential space for human
with an elderly or a middle aged non-faller during descending stairs of a pedestrian
communications between elderly residents living
bridge
(T Katsura, N Miura, N Takahashi, S Hisamoto and A Hoshino )
alone in communities for the purpose of social
❷
BMI curve in males (above) and females (below) of 400,000 Japanese aged 25-75
experimentation on building a healthy community.
( T Katsura, K Matsuda, M Yamazaki and A Hoshino )
This includes health promotion of community
❸ “Sukoyaka” health lectures aiming at successful aging are held to promote health of
residents, and supporting resident-participant health
community residents about 6 times for a year in Kyoto
promotion activities and framing of community
networks.
Recent Publications
Preventive Nursing
Professor : Toshiki Katsura , R.P.H.N. , R.N. , Ph.D.
Senior
Lecturer : Mika Okura
Assistant
Professor : Kanae Usui , R.P.H.N. , R.N. , M.N.S.
: See page 000-000
1. Toshiki Katsura, Akiko Hoshino : Factors Relating to Maintenance of Walking to prevent against
House-boundedness in Old-old-residents. J. J. H. M.;16(1):14-24, 2007.
2. Toshiki Katsura, Kazumi Matsuda, Mari Yamazaki, Akiko Hoshino : A Follow-up Study on
Weight Management Appropriate for Improving Coronary Risk Factors – Does Moderate Middletermed Weight Loss Improve Hypercholesterolemia ? -. J.J. H. M.;15(4):3-14, 2007.
3. Toshiki Katsura, Kazumi Matsuda, Mari Yamazaki, Akiko Hoshino. Prevalence of Metabolic
Syndrome in 400,000 Japanese Employees Resided in All Prefectures, Japan; J.H.M.A. : 14(4), 2-6,
2006.
4. Akiko Hoshino, Toshiki Katsura, Masae Yamamoto : Examination of a Satellite System at a Local
Shopping Center for Supporting Independent Living of Elderly People – SUKOYAKA Salon -. J. J.
R. M.;55(4):402-407, 2006.
5. Toshiki Katsura, Akiko Hoshino : Characteristics of Independent Moving Ability in Elderly
Residents – Comparison of Physical Factors Relating to Walking Ability between young-old and
old-old-residents-. J. J. H. M.;14(4):16-23, 2006.
6. Akiko Hoshino, Toshiki Katsura : Effects of Activities of Community Organization in a Local
city –Comparison of Health Behaviors of Continuators and Those of Retirees of Hoken-suisinin
Activities in F-city -.J. J. H. M.;14(2):33-36, 2005.
- Nursing Science - Community Health and Community Health Nursing
As the population ages, the need to fully understand the pathogenesis of dementia and to develop its effective method for care is
vital to our nation. Therefore, the mission of our section is to help the person with the disease, and caregivers, family members to
empower the abilities that remain. Within this mission, one objective is to foster new lines by bringing together basic and clinical
science with an emphasis on Alzheimer’s disease and related disorders. We welcome the young scientists who have interests in
dementia research.
Ayae Kinoshita, MD, PhD
Professor
1)Pathogenesis of Alzheimer’s disease
The exact nature of neuronal dysfunction in
Alzheimer’s disease remains largely unknown.
For the last 10 years, we have focused on the
protein Presenilin 1 (PS1), a causative protein for
familial Alzheimer’s disease in order to reveal its
pathogenesis. We are now currently pursuing the
mechanisms which influence the PS1 localization
and functions. We identified several factors to
regulate PS1 function and are now currently
analyzing them in vitro and in vivo.
2)Development of internet-based telenursing
In order to support the homecare for the dementia
patients, there is a need for the bi-directional,
communicative and economical approach between
the patients and the medical staff. We develop and
provide a new strategy to help the dementia patients
and caregivers by internet-based webcamera.
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❶ The research of the N-cadherin
cleavage by Presenilin 1. The PS1mediated N-cadher in cleavage
releases its cytoplasmic domain from
the membrane and transactivate betacatenin. PS1 is considered to have an
important effect on regulating signal
transduction.
❷ Our hypothesis of Alzheimer’s disease
pathogenesis. PS1 dysfunction may be
causally linked to synaptic failures and
other neuronal damages. We consider
PS1 as a molecular switch to regulate
various signaling cascades by cleaving
membranous proteins.
❸ An example of a new IT-based support
system for the dementia patients and
caregivers.
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Recent Publications
Professor : Ayae Kinoshita
Assistant
Professor : Masakazu Kubota
: See page 000-000
Kyoto University
1. 木下彩栄老年性認知症「ガイドライン外来診療 2009」日経メディカル p395-402
2. Uemura K, Lill CM, Banks M, Asada M, Aoyagi N, Ando K, Kubota M, Kihara T, Nishimoto T,
Sugimoto H, Takahashi R, Hyman BT, Shimohama S, Berezovska O, Kinoshita A. N-cadherinbased adhesion enhances Abeta release and decreases Abeta42/40 ratio.J Neurochem. 2009,
108:350-60
3. スカイプと Web カメラを使用した在宅認知症患者とその介護者への支援：保利美也子、
久保田正和、木下彩栄癌と化学療法、35 (1) 46-47. 2008
4. 植村健吾、安藤功一、久保田正和、木下彩栄：gamma セクレターゼとシナプス機能 Cognition & Dementia 7, 46-54 (2008).
5. Uemura, K., Kuzuya, A., Shimozono, Y., Aoyagi., N., Ando, K., Shimohama, S., & Kinoshita, A.
GSK3beta activity modifies the localization and function of presenilin1. J Biol.Chem. 282, 1582332 (2007).
6. Uemura K., Kuzuya, A., Aoyagi, N., Ando, K., Shimozono, Y., Ninomiya, H., Shimohama, S.,
Kinoshita, A. Amyloid beta inhibits ectodomain shedding of N-cadherin via down-regulation of
cell-surface NMDA receptor. Neuroscience 145:5-10 (2007)
7. Uemura, K., Kihara T., Kuzuya, A., Okawa, K., Bito H, Ninomiya H, Sugimoto H, Shimohama S.,
and Kinoshita, A: Modulation of beta-catenin nuclear signaling via epsilon-cleavage of N-cadherin.
Biochem Biophys Res Commun 345:951-8 (2006)
8. Uemura, K., Kihara T, Kuzuya, A., Okawa, K., Sugimoto H, Shimohama S., and Kinoshita, A:
Characterization of N-cadherin cleavage by ADAM10 and Presenilin 1. Neurosci Lett.402:278-13
(2006)
- Laboratory Science - Medical Laboratory Science
A human body consists of a number of cells called 60 trillion. These cells interact each other and response for environmental
signal to form a precise human body system. We are trying to understand various biological phenomena involving this system
with a molecular level, especially by focusing on carbohydrates expressed on proteins. Moreover, we hope that the result of our
research can contribute to develop a diagnosis at super-early stage of disease. We would like to advance research with young
students having a dream.
Shogo Oka, Kuniaki Saito
Professor
Decoding of the biological information in sugar
chains (Oka):
The function of proteins is regulated in vivo not
only by transcriptional control of gene expression
but also by post-translational modifications.
Glycosylation is one of the major post-translational
modifications and a large number of proteins, in
fact, undergo this modification. In the post-genomic
era, it is very important to decode the biological
information encoded in the sugar chains. In our
project we focus on structure and function of sugar
chains expressed in the nervous system and in
development during embryogenesis. To elucidate the
roles of the HNK-1 carbohydrate expressed in the
nervous system, we have succeeded in generating
GlcAT-P gene-deficient mice. The GlcAT-P -/- mice
exhibited reduced long-term potentiation (LTP) at
the Schaffer collateral-CA1 synapses and defects in
spatial memory formation.
The physiological significance of IDO in CNS
disorders (Saito):
Indoleamine-2,3-dioxygenase(IDO) production
by macrophages and dendritic cells has recently
been demonstrated to result in the inhibition of T
cell proliferation due to tryptophan depletion by
this enzyme. A schematic diagram illustrating the
possible role of IDO induction in inflammatory
CNS disorders is shown in the figure. IDO plays an
important physiological role (both beneficial and
detrimental) in the CNS. It has become clear that
IDO expression in the CNS is more complicated,
to be sure, but regulation of IDO induction must be
an ideal therapeutic target to modulate symptoms of
various CNS disorders.
Study on acute inflammation associated with
transplant rejection (Ikemoto):
f fWe found a protein that remarkably increased
in the serum of the recipients with transplant
rejection. This protein is produced by macrophage
and/or activated neutrophils in an early stage of
acute inflammation, although its functional role
remains unclear. We recently found that the protein
could indirectly regulate excessive inflammatory
responses by binding with inflammatory cytokines
nonspecifically. Our goal is to resolve expression
mechanism and functional role of the protein in these
immunological cells.
Recent Publications
Professor : Shogo Oka, Kuniaki Saito
Associate
Professor : Masaki Ikemoto
Assistant
Professor : Yasuko Yamamoto
: See page 000-000
1. Tagawa, H. et al. (2005) Non-sulfated form of the HNK-1 carbohydrate is expressed in mouse
kidney. J. Biol. Chem. 280, 23876-23883.
2. Fujigaki H, Saito K (2006) Nitration and inactivation of indoleamine-2,3-dioxygenase by
peroxynitrite.J Immunol. 176:372-379.
3. Shiba, T. et al. (2006) Crystal structure of GlcAT-S, a human glucuronyltransferase, involved in the
biosynthesis of the HNK-1 carbohydrate epitope. Proteins 65, 499-508.
4. Kizuka, Y. et al. (2006) Physical and functional association of glucuronyltransferases and
sulfotransferase involved in HNK-1 biosynthesis. J. Biol. Chem. 281, 13644-13651.
5. Ikemoto, M. et al. (2007) Intrinsic function of S100A8/A9 complex as an anti-inflammatory
protein in liver injury induced by lipopolysaccharide in rats. Clin. Chim. Acta. 376, 197-204.
- Laboratory Science - Medical Labolatory Science
The cause of diseases can be largely classified into tumor, infection, heredity, hemodynamic disorder, immune disorder,
metabolic disorder, and environmental factor, while we focus our researches on tumor, heredity, and infection. Our objective is to
study the nature of diseases regardless of the field of laboratory testing, and we believe the outcome will help the development of
laboratory testing studies. We educate students about these causes of diseases through lectures and experiments. We coordinate
with the department of clinical laboratory and the department of diagnostic pathology so that we can integrate basic and clinical
medicine.
Tetsuya Takakuwa
Professor
1. Analysis of spontaneous B-cell lymphoma forming
mice (collaboration with Forensic Medicine and
Molecular Pathology, Graduate School of Medicine)
(Takakuwa)
To identify genes responsible for lymphoma
formation, by analyzing SL/Kh mice which
spontaneously form pre B-cell lymphoma more than
90% by six months old.
2. Analysis of the pathology and the developmental
mechanism in inborn errors (collaboration with
Congenital Anomaly Research Center, Graduate
School of Medicine) (Takakuwa)
Congenital Anomaly Research Center stores several
ten thousands of human embryo samples. To
explore normal human development and find novel
abnormalities and diseases, and the cause of them,
by utilizing non-invasive, 3-dimensional analysis
method like MR imaging and EFIC imaging.
3. Application of novel 3-dimensional morphological
analysis method to pathological diagnosis
(collaboration with Congenital Anomaly Research
Center, Graduate School of Medicine) (Takakuwa)
To apply non-invasive, 3-dimensional analysis
method like MR imaging and EFIC imaging to
pathological diagnosis.
4. Mechanism of humoral immune response against
retrovirus infection (Ibuki)
We are trying to develop an extremely sensitive
ELISA for measurement of an anti-virus specific
antibody against SIV or SHIV and with it, examine
whether humoral immunity is related to control of
the virus multiplication in the monkeys infected with
SIV or SHIV.
5. Study on the mechanism of resistance against
anti-HIV-1 drugs using SHIV-monkey model.
(collaboration with Lab. for Viral Replication, I.V.R.)
(Ibuki)
To elucidate the acquisition mechanism of drugresistance of HIV-1 during ART (anti-retroviral
therapy), we analyze the viral mutation in rhesus
macaques infected with SHIV having the HIV-1 pol
gene before and after ART.
Professor : Tetsuya Takakuwa
Associate
Professor : Kentaro Ibuki
: See page 000-000
Kyoto University
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❶ Stage 56 Embryo MR imaging.
❷ Virus particle and genome structure
of SHIV.
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Recent Publications
1. Richard H. Kaszynski Takakuwa T et al, A quantitative trait locus responsible for inducing B-cell
lymphoblastic lymphoma is a hotspot for microsatellite instability, Cancer Sci, in press
2. Oji Y, Takakuwa T, et al, WT1 IgG antibody for early detection of nonsmall cell lung cancer and
as its prognostic factor. Int J Cancer. 2009;125(2):381-7. 2.
3. Takakuwa T, et al, Aberrant somatic hypermutations in thyroid lymphomas, Leukemia
Research2009 ;33(5):649-54.
4. Nur Rahadiani; Takakuwa T, et al, Latent membrane protein 1 of Epstein-Barr virus induces the
expression of B-cell integration cluster, a precursor form of microRNA-155, in B lymphoma cell
lines, BBRC, 2008;377(2):579-83.
5. Fukazawa Y, Miyake A, Ibuki K, Inaba K, Saito N, Motohara M, Horiuchi R, Himeno A, Matsuda
K, Matsuyama M, Takahashi H, Hayami M, Igarashi T, Miura T.: Small intestine CD4+ T cells are
profoundly depleted during acute simian-human immunodeficiency virus infection, regardless of
viral pathogenicity. J Virol. 2008 82(12):6039-44.
6. Liu A, Takakuwa T, Fujita S, Luo WJ, Tresnasari K, van den Berg A, Poppema S, Aozasa K:
ATRalterations in Hodgkin's lymphoma. Oncology Report 19(4):999-1005, 2008.
7. Takakuwa T, Tresnasari K, Rahadiani N, Miwa H, Daibata M, Aozasa K, Cell origin of pyothoraxassociated lymphoma; a lymphoma strongly associated with Epstein-Barr virus infection,
Leukemia, 22(3):620-7, 2008.
- Laboratory Science - Medical Laboratory Science
Laboratory science aims to establish and realize concepts and methods for extracting and analyzing various information from
molecular and cellular levels to the organ level, for the purpose of elucidating structure and function of livings, clarifying
etiology and pathophysiology of various diseases and establishing diagnosis and treatment of diseases. In this area, we focus on
structural and functional analysis indispensable for diagnosis of treatment of diseases. Accordingly, we promote studies on new
concept and technology on the basis of medicine, biology and information technology. We intend to encourage new talents who
will act as a leader in the fields of education, research and clinical practice.
Souichi Adachi, Akihiko Nakaizumi, Masatoshi Fujita
Professor
【Adachi Labo】
Many hematologic malignancies of children have
been cured because of progression of treatments. But,
still some of these patients relapse or suffer serious
complications. Our laboratory has many projects
related with new treatments or diagnostic tools in
these patients.
(1) Mechanism of new type of cell death induced by
molecular target therapy
(2) Development of new treatments and new
prognostic factors in child AML
(3) Analysis of serious complications in patients after
stem cell transplantation.
【Nakaizumi Labo】
Our aim is to bring up a talented person familiar
with various laboratory examinations related to
pancreatobiliary malignancies. I hope that he/
she will play an active role as an equal partner of
gastroenterologist in the clinical setting.
Our laboratory has many projects related with new
diagnostic tools or treatments in the patients with
pancreatobiliary malignancies.
(1) Early diagnosis of pancreatobiliary malignancies
(2) Endoscopic diagnosis and treatments
(3) Analysis of the high risk group for pancreatic
cancer and development of the medical checkup
system for the early detection of pancreatic cancer
(4) Conventional or rapid cytological examinations
in digestive malignancies.
【Fujita Labo】
Our aim is to bring up a talented person familiar
with various laboratory examinations related to
cardiovascular disease. I hope that he/she will play an
active role as an equal partner of cardiologist in the
clinical setting.
1)Development of acceleration bed for improving
QOL of elderly
2)Significance of smoking as a deteriorating factor of
chronic fatigue syndrome
3)Development of molecular targeting treatment for
heart failure with administration of curcumin
Professor : Souichi Adachi, Akihiko Nakaizumi,
Masatoshi Fujita
Assistant
Professor : Hiroshi Itoh
List for Tel, Fax& E-Mail
: See page 000-000
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❶ Adachi's Lab
❷ Fujita's Lab
❸ Nakaizumi's Lab
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Recent Publications
1. Watanabe M, Adachi S, Matsubara H, Imai T, Yui Y, Mizushima Y, Hiraumi Y, Watanabe K,
Kamitsuji Y, Toyokuni S, Hosoi H, Sugimoto T, Toguchida J, Nakahata T: Induction of autophagy
in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF
translocation. Int J Cancer 124:55-67, 2009
2. Kamitsuji Y, Kuroda J, Kimura S, Toyokuni S, Watanabe K, Ashihara E, Tanaka H, Yui Y,
Watanabe M, Matsubara H, Mizushima Y, Hiraumi Y, Kawata E, Yoshikawa T, Maekawa T,
Nakahata T, Adachi S: The Bcr-Abl kinase inhibitor INNO-406 induces autophagy and different
modes of cell death execution in Bcr-Abl-positive leukemias. Cell Death Differ 15:1712-1722,
2008
3. H Uehara, A Nakaizumi, O Ishikawa, H Iishi, K Tatsumi, R Takakura, T Ishida, Y Takano, S
Tanaka, A Takenaka. Development of ductal carcinoma of the pancreas during follow-up of branch
duct intraductal papillary mucinous neoplasm of the pancreas. Gut 2008 Nov; 57: 1561-5
4. H Uehara, K Tatsumi, E Masuda, M Kato, T Kizu, T Ishida, R Takakura, Y Takano, A Nakaizumi,
O Ishikawa, A Takenaka. Scraping cytology with a guidewire for pancreatic-ductal strictures.
Gastrointest Endosc. 2009 Feb; 25
5. Fukuda S, Shimada K, Kawasaki T, Kono Y, Jissho S, Taguchi H, Maeda K, Yoshiyama M, Fujita
M, Yoshikawa J: “Passive exercise” using whole body periodic acceleration: effects on coronary
microcirculation. American Heart Journal 159(4):620-626, 2010.
6. Miyamoto S, Fujita M, Inoko M, Oba M, Hosokawa R, Haruna T, Izumi T, Saji Y, Nakane E,
Abe T, Ueyama K, Nohara R: Effect on treadmill exercise capacity, myocardial ischemia, and
left ventricular function as a result of repeated whole-body periodic acceleration with heparin
pretreatment in patients with angina pectoris and mild left ventricular dysfunction. The American
Journal of Cardiology 107(2):168-174, 2011.
7. Miwa K, Fujita M: Fluctuation of serum vitamin E (α-tocopherol) concentrations during
exacerbation and remission phases in patients with chronic fatigue syndrome. Heart and Vessels
25(4):319-323, 2010.
8. Ohigashi H, Ishikawa O, Eguchi H, Takahashi H, Gotoh K, Yamada T, Yano M, Nakaizumi
A, Uehara H, Tomita Y, Nishiyama K: Feasibility and efficacy of combination therapy with
preoperative full-dose gemcitabine, concurrent three-dimensional conformal radiation, surgery, and
postoperative liver perfusion chemotherapy for T3-pancreatic cancer. Ann Surg. 250:88-95.2009
- Laboratory Science - Information Technology and Medical Engineering
[Akitoshi Seiyama (Professor)]
We are developing new technologies to visualize biophysical and physiological functions inside the living body, especially
to visualize human brain function. Further, we aim to reveal mechanisms of such individual bio-phenomena through animal
experiments.
[Satoshi Sasayama (Associate Professor)]
We are conducting various data analysis and information system development by utilizing statistics and ergonomics.
Specifically, we are constructing a pathogenic bacteria database, an e-Learning system, and some interactive learning materials
in the fields of health science.
Akitoshi Seiyama
Professor
[Akitoshi Seiyama (Professor)]
We are developing new technologies to visualize
biophysical and physiological functions inside the
living body. In vivo molecular imaging, an important
technique in the post-genome strategy, has the
potential to visualize the dynamics of individual biophenomena processes in cells, organs as well as in the
living body. We aim to reveal mechanisms of such
individual bio-phenomena in the living body through
bio-imaging using MRI, Near-IR optical imaging and
electrophysiological techniques.
[Satoshi Sasayama (Associate Professor)]
We are constructing a pathogenic bacteria
database (PBDB) to provide the basic knowledge
on bacteriology not only to the researchers and
specialists on microbiology but also to students and
general public through the Internet. This system
serves picture information, such as high-quality
images of bacteria and of analysis materials, moving
images with narration of assay procedures, and so
on. We are also constructing an e-Learning system,
and some interactive learning materials intended for
students and alumni of health science.
Recent Publications
Professor : Akitoshi Seiyama
Associate
Professor : Satoshi Sasayama
: See page 000-000
Kyoto University
1. Jin T, Fujii F, Komai Y, Seki J, Seiyama A, Yoshioka Y: Preparation and Characterization of Highly
Fluorescent, Glutathione-coated Near Infrared Quantum Dots for In Vivo Fluorescence Imaging.
Int J Mol Sci 9(10):2044-2061, 2008
2. Jin T, Yoshioka Y, Komai Y, Seki J, Seiyama A: Gd3+-Functionalized Near-Infrared Quantum Dots
for In Vivo Dual-modal (Fluorescence/Magnetic Resonance) Imaging. Chem Commun (Camb)
30(44): 5764-5766, 2008
3. Seiyama A: Dissociation of Stimulus-Induced Responses in Regional Cerebral Blood Flow and
Blood Volume in the Visual Cortex of Humans. 健康科学 4: 7-18,2007
4. Kohno S, Miyai I, Seiyama A, Oda I, Ishikawa A, Tsuneishi S, Amita T, Shimizu K: Removal of the
skin blood flow artifact in functional near-infrared spectroscopicimaging data through independent
component analysis. J Biomed Opt 12: 062111(1-9), 2007
5. Li JY, Ueda H, Seiyama A, Seki J, Konaka K, Yanagida T, Sakoda S, Yanagihara T: Ischemic
vasoconstriction and tissue energy metabolism during global cerebral ischemia in Gerbils. J
Neurotrauma 24: 547-558,2007
- Information Technology and Medical Engineering
Innovative Medical Imaging Technology
Among biomedical imaging technologies, image information processing applicable to computer assisted diagnosis and ultra
high resolution MRI are focused in this group. Medical image data obtained from such as CT and MRI becomes larger so as to
provide medical staff with higher quality images. One of our objectives is to develop image information processing algorithm
and systems to assist doctors in extracting necessary information from the huge data by more precise and more effective way. In
order to obtain molecular/cell level information, we are also developing the ultra high resolution MRI equipment.
Naozo Sugimoto, PhD (in Eng.)
Professor
* Biomedical imaging devices
We have been developing an ultra high resolution
Magnetic Resonance Imaging (MRI) as a
microscopy, "MRI Microscopy". Among imaging
technologies, MRI is in an unique position due to
its abilities to localize activating parts in biomedical
specimen and to distinguish tissue non-invasively.
With the MRI Microscopy, we could understand
human brain functional images from the molecular
and cell biological point of view. We started to
develop a new MRI Microscope for small biological
tissue using a 14.1 T horizontal bore magnet and a
600 MHz NMR spectrometer.
* Image processing methods and its medical
applications
We develop image processing techniques for
quantitative analysis of multi dimensional
medical images including multi modality images
or sequential images. We also develop medical
applications such as image guided radiotherapy,
image guided intervention, CAD(computer aided
diagnosis) system, and so on. An example of
the work is shown in the right column figure
(4-dimensional cardiac MR tagged imaging and
5-dimensional image processing methods).
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❶ Four-dimensional cardiac MR
tagged imaging and image
processing.
❷ Previously developed MR
microscope with 7-T magnet.
❸ Staff with 14-T MR magnet for
a new MR microscope.
Recent Publications
Innovative Medical Imaging Technology
Professor : Naozo Sugimoto, Ph.D.
Assistant
Professor : Tomohiro Ueno, Ph.D.
: Koji Sakai, Ph.D.
: See page 000-000
1. S. Urayama, N. Sugimoto, et al., Four-dimensional MR tagged imaging and image processing.
International Journal of Computer Assisted Radiology and Surgery, Vol. 1-Suppl., pp.107109(2006)
2. H. Sekiguchi, N. Sugimoto, et al., An image processing on regular coronary angiograms for
myocardial perfusion measurement. Computers in Cardiology, Vol.33, pp.821-824(2006)
3. F. Voci, S. Eiho, N. Sugimoto, and H. Sekiguchi, Estimating the gradient threshold in the PeronaMlik equation. IEEE Signal Processing Magazine, Vol.21, No.3, pp. 39-46(2004)
4. T. Ueno, S. Balibar, T. Mizusaki, F. Caupin, E. Rolley, Critical Casimir effect and wetting by
helium mixtures. Physical Review Letter 2003;90:116102.
5. T. Ueno, M. Fujisawa, K. Fukuda, Y. Sasaki, and T. Mizusaki, Visualization of phase-separated
boundary in liquid 3He-4He mixtures by MRI, Physica B 284-288, 2057-2058 (2000).
- Laboratory Science - Information Technology and Medical Engineering
Medical Imaging System Sciences
Aiming to earlier diagnosis, improved accuracy of diagnosis and adequate treatment support, in our laboratory, we have
researched advanced medical equipment. The topics being studied cover both of the fundamental research and clinical
application. The former includes developing real-time and non-invasive sensing and imaging of biomedical information,
which is relevant to tissue characteristics and function in addition to morphology. The latter includes applications of advanced
ultrasound and optical imaging technology to diagnosis and minimally-invasive treatment support of diseases such as beast
cancer, chronic hepatitis, myocardial infarction.
Tsuyoshi Shiina, PhD (in Eng. & Med. Sci)
Professor
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Nowadays, non-invasive imaging equipment such
as CT, MRI, US is indispensable to medical care.
However, diagnostic information about tissue
characteristics and function is insufficient compared
with morphological information. Then, there is a
real need for development of advanced medical
imaging modalities for earlier diagnosis and more
accurate differential diagnosis. In our laboratory,
using ultrasound which has the advantage of
being non-invasive, real-time, many biomedical
imaging technologies such as 3-D blood flow
vector imaging, myocardial contractility imaging
have been investigated. As for imaging of tissue
❹
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characteristics, real-time tissue elasticity imaging
has been developed in our laboratory and world’s
first practical use of elasography for breast cancer
diagnosis was achieved in collaboration with
industries and university.
In recent years, we started research on novel
non-invasive imaging modality which combines
ultrasound and optics, in the project ‘Innovative
❸
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Techno-Hub for Integrated Medical Bio-imaging’
❶ Ultrasound tissue elasticity imaging
financed by JST and MEXT.
equipment(elasography)
Including this, we are now working the following
❷ Elastogram of breast cancer(non-invasive
research topics.
ductal carcinoma )
(1)Ultrasound tissue elasticity imaging
❸ Assessment of coronary plaque using IVUS
a)Breast cancer, prostate cancer diagnosis
elastography
❹ Ubiquitous medical image diagnosis
b)Quantitative assessment of arteriosclerosis
c)Staging of fibrosis and CAD for hepatic cirrhosis
(2)Myocardial contractility imaging
(3)3-D blood flow imaging
(4)Fusion technology of ultrasound and optical
imaging
(5)Ubiquitous medical image diagnosis
(6)Theory for non-invasive biomedical measurement
and medical imaging analysis.
Through these research works, we also aim to
foster human resource to be active in wide fields
from development of medical equipment to clinical Recent Publications
1. H. Nakagawa, S. Ueno, T. Shiina, M. Kotani, S. Kubota, "Application of radical chain reactions
practice.
Medical Imaging System Sciences
Professor : Tsuyoshi Shiina
Associate
Professor : Kenichi Otsuka
: Shuhui Bu
: See page 000-000
Kyoto University
to drug release controlling of liposomal carriers under high magnetic fields," Journal of Applied
Physics, Vol. 105, 07B323, 2009.
2. T. Shiina, M. Yoshida, M. Yamakawa, N. Nitta: “Microscopic Measurement of Three-Dimensional
Distribution of Tissue Viscoelasticity,” Acoustical Imaging, pp.11-18, 2008.
3. T. Shiina: “In vitro 3-D Measurement of Tissue Viscoelasticity by Ultrasound”, Int. Journal of
Appl. Biomed. Eng. Vol.1, No.1, pp.1-6,2008.
4. H. Nakagawa, T. Shiina, M. Sekino, M. Kotani, S. Ueno: “Fusion and Molecular Aspects of
Liposomal Nanocarriers Incorporated with Isoprenoids,” IEEE Trans. NanoBioscience, Vol. 6, pp.
219-222, 2007.
5. A. Itoh, E. Ueno, E. Tohno, H. Kamma, H. Takahashi, T. Shiina, M. Yamakawa, T. Matsumura:
“Breast Disease: Clinical Application of Ultrasound Elastography for Diagnosis,” Radiology, Vol.
231, No. 2, pp. 341-350, 2006.
- Rehabilitation Sciences - Physical Therapy, Rehabilitation Sciences
Our laboratory has made a significant progress in research of motor function using morphological, biochemical, physiological
and biomechanical methodology. From the standpoint of rehabilitation, nervous system, skeletal muscles and articular cartilage
are especially studied in our laboratory and a novel walking assist system is also studied in the clinical field of elderly persons
and patients with osteoarthritis. In the near future, research in community and sports fields will be started. The aim of our
laboratory is to bring up talented young scientists who can promote studies in prevention for disease and who can contribute to
rehabilitation for minimizing functional disabilities based on elucidation of mechanisms of disease and disabilities.
Hiroshi Kuroki, Makoto Ishibashi
Professor
Recent studies in our laboratory have revealed novel
evidences on properties of ultrasound echo from
articularcatilage, roles of Sonic hedgehog (Shh)
signaling,and properties of the skeletal muscle of cerebral
palsy. Based on these achievements, we are currently
pursuing the following research projects.
1) Because articular cartilage has limited healing capacity,
the cartilage of osteoarthritis rarely repair spontaneously.
Raw wave of ultrasound echo from articular cartilage and
its wavelet transform reveals features of acoustic properties
in such osteoarthritic cartilage and postoperative cartilage
(Figure 1). Our ultrasound assessment for articular cartilage
is one of the advanced research projects in the world.
Relationship between ultrasound echo and collagen is also
studied. Based on these evidences, rehabilitation for human
knee cartilage and prevention of functional disability of
knees are promoted in our clinical field.
2) A novel walking-assist system is studied. In this system
the elderly persons and patients with osteoarthritis can walk
with low energy and without joint pain because their body
weight can be reduced to 25 % using positive air pressure
(Figure 2).
3) In order to understand how the head region and the
central nervous system are patterned during embryogenesis,
specifically, we analyze the knock-out mice to examine
roles of Sonic hedgehog (Shh) signaling in formation
of the brain (Figure 3). FGF signaling is also being
analyzed to elucidate the mechanisms of how the head
region is determined. In addition, mathematical models
are hypothesized and tested by experiments to clarify the
behaviors of signaling molecules.
4)Walking training for the patients with central nervous
system disorders and muscle strengthening for the children
with central nervous system disorders are studied.
5) Psychological process in palliative medicine and terminal
care for the cancer patients is studied.
6) Rehabilitation approach and assessment for the elderly
people is studied.
In pursuing these research projects, we focus on training
of scientists in a wide variety of techniques in ultrasound
measurement of articular cartilage, histopathology of
degenerated cartilage, chondrocyte culture, and gait
rehabilitation as well as up-to-date knowledge in the related
fields. We welcome young students to our laboratory
and hope them working together to create new aspects in
rehabilitation research.
Professor : Hiroshi Kuroki, Makoto Ishibashi
Senior
Lecturer : Koji Ohata
Yuko Maeda
Assistant
Professor : Tome Ikezoe
: See page 000-000
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❶ Raw waves of echo from articular cartilage (bottom) and wavelet transform (top)
❷ A novel walking assist system using positive air pressure
❸ Expression of Sonic hedgehog (Shh) in chick embryo (in situ hybridization)
Recent Publications
1. Ohata K, Tsuboyama T, Haruta T, Ichihashi N, Nakamura T. Longitudinal change in muscle and fat
thickness in children and adolescents with cerebral palsy. Dev Med Child Neurol. 2009; May 11.
[Epub ahead of print]
2. Kuroki H, Nakagawa Y, Mori K, Kobayashi M, Yasura K, Okamoto Y, Suzuki T, Nishitani
K, Nakamura T. Ultrasound has the potential to detect degeneration of articular cartilage
clinically, even if the information is obtained from an indirect measurement of intrinsic physical
characteristics. Arthritis Res Ther. 2009;11(3):408.
3. Kuroki H, Nakagawa Y, Mori K, Kobayashi M, Nakamura S, Nishitani K, Shirai T, Nakamura
T. Ultrasound properties of articular cartilage immediately after osteochondral grafting surgery:
in cases of traumatic cartilage lesions and osteonecrosis. Knee Surg Sports Traumatol Arthrosc.
2009;17(1):11-8.
4. Maeda Y, Kobori E, Kubota Y, Seki S, Takada K, Kuramoto N, Hiraide A, Morimoto T. Major
qualitative research methods in patient-doctor communication studies. Gen Med 2008;9(1):5-12.
5. Komada M, Saitsu H, Kinboshi M, Miura T, Shiota K, Ishibashi M. Hedgehog signaling is
involved in development of the neocortex. Development. 2008;135(16):2717-27.
6. Miura T, Hartmann D, Kinboshi M, Komada M, Ishibashi M, Shiota K: The cyst-branch difference
in developing chick lung results from a different morphogen diffusion coefficient. Mech Dev.
2009;126:160-172.
7. Kuroki H, Nakagawa Y, Mori K, Kobayashi M, Yasura K, Okamoto Y, Suzuki T, Nishitani
K, Nakamura T. Ultrasound properties of articular cartilage in the tibio-femoral joint in knee
osteoarthritis: relation to clinical assessment (International Cartilage Repair Society grade).
Arthritis Res Ther. 2008;10(4):R78.
8. Komada M, Saitsu H, Shiota K, Ishibashi M. Expression of Fgf15 is regulated by both activator
and repressor forms of Gli2 in vitro. Biochem Biophys Res Commun. 2008;369(2):350-6.
9. Ohata K, Tsuboyama T, Haruta T, Ichihashi N, Kato T, Nakamura T. Relation between muscle
thickness, spasticity, and activity limitations in children and adolescents with cerebral palsy. Dev
Med Child Neurol. 2008;50(2):152-6.
- Rehabilitation Sciences - Physical Therapy, Rehabilitation Sciences
Development and Rehabilitation of Motor Function
Rehabilitation is the process of developing oneself again so that one can show the highest ability in daily living. Rehabilitation
creates a new life. Importance is being added to rehabilitation with the increasing application of advanced medical treatment
and change in the structure of society. We try to promote research on the mechanisms of motor dysfunction, the development
of new function, and compensatory methods assisted by up-to-date technology. With these approaches, we are aiming at the
establishment of advanced rehabilitation systems.
TadaoTsuboyama, Noriaki Ichihashi,
Professor
We intend to produce excellent rehabilitation
professionals who, with broad horizons, can
cope with many problems in both clinical and
social settings. We proceed with research in
cooperation with Kyoto University Hospital on the
theoretical aspects of motor disability and practical
reconstructive strategies. Specific themes are as
follows:
1.Analyses of functional disorders caused by
musculoskeletal diseases.
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2.Clinical and biomechanical investigations on the
physiotherapy of the locomotor system.
3.Evaluation systems for physiotherapy.
4.Investigation on stretching
5.Investigation on training effectiveness
6.Analyses of the factor of falling in elderly people.
7.Investigation to prevent falling; exercise training.
❶ Analyses of biomechanics; 3-dimentional optical operating analysis, ground reactive
force monitor, electro-myogram
❷ Ultrasound image
❸ 3-dimensional gait analysis using treadmill without loading pressure
❹ Sitting pressure
Recent Publications
Development and Rehabilitation of Motor
Function
Professor : Noriaki Ichihashi, TadaoTsuboyama
Associate
Professor : Tomoki Aoyama
Assistant
Professor : Hiroshige Tateuchi, Minoru Yamada
: See page 000-000
Kyoto University
1. Tateuchi H, Tsukagoshi R, Fukumoto Y, Oda S, Ichihashi N.: Dynamic hip joint stiffness in
individuals with total hip arthroplasty: Relationships between hip impairments and dynamics of the
other joints. Clinical Biomechanics. 2011(in press)
2. Ikezoe T, Mori N, Nakamura M, Ichihashi N. : Atrophy of the lower limbs in elderly women: is it
related to walking ability? European journal of applied physiology. 2011 (in press)
3. Nagai K, Inoue T, Yamada Y, Tateuchi H, Ikezoe T, Ichihashi N, Tsuboyama T. : Effects of toe and
ankle training in older people: A cross-over study. Geriatr Gerontol Int. 2011(in press)
4. Ohata K, Yasui T, Tsuboyama T, Ichihashi N. : Effects of an ankle-foot orthosis with oil damper on
muscle activity in adults after stroke. Gait Posture. 2011 Jan;33(1):102-7.
5. Yamada M, Tanaka B, Nagai K, Aoyama T, Ichihashi N. : Trail-walking exercise and fall risk
factors in community-dwelling older adults: preliminary results of a randomized controlled trial. J
Am Geriatr Soc. 2010 Oct;58(10):1946-51.
- Rehabilitation Sciences - Occupational Therapy
The rehabilitation has become very important in countries facing severe population aging. We aim at improving quality of life of
clients with physical, psychological, cognitive or developmental limitations and are studying functional recovery for improved
quality of life using various techniques in neuroscience, such as brain imaging techniques. Such an approach requires us to join
multidisciplinary forces including occupational and physical therapies. We welcome young enthusiastic students interested in
rehabilitation sciences regardless of their educational backgrounds.
Motomi Toichi, Toshiko Futaki, Akira Mitani
Professor
Our group consists of three laboratories.
In Aging, Environment and QOL research lab, we
focus on exploring issues related to older adults'
cognitive functioning and activity in every day living
in a variety of environments including community,
long-term and institutional living situations from
the perspective of consumers, family members and
health care providers. We have also explored issues
in aging with an intellectual disability and adaptation
from cognitive neuroscientific perspectives (Fig. 1).
In Cognitive Neurophysiology lab, we aim at the
clarification of neural and cognitive mechanisms
that underlie clinical and behavioral problems
associated with psychiatric and developmental
disorders, which include schizophrenia, mood
disorder, autistic disorder, Asperger’s disorder and
AD/HD. Our main research technique consists of
electroencephalography, event-related potentials,
near-infrared spectroscopy, functional MRI as well
as cognitive psychological measurements. We try to
incorporate our findings into the therapeutic practice
in order to establish more effective and evidencebased intervention (Figs. 2, 3).
In Neuroscience lab, we focus on a neural
mechanism of functional recovery providing a neural
substrate to underpin rehabilitation and try to develop
novel rehabilitation strategies (neuroscience-based
rehabilitation). We record magnetoencephalographic
(MEG) signals from stroke patients to examine
cortical reorganization corresponding to improved
motor and sensory performance of the paretic limb
(Fig. 4). We also investigate the plasticity of neural
network underlying recovery of brain function using
animal models.
❶ What do you interpret the picture
relevant to “person-environmentoccupation”? How do you make
an approach the complexity and
multiple interactions from cognitive
neuroscientific perspective?
❷ Optical imaging system using nearinfrared spectroscopy.
The optical technique enables us to
non-invasively measure hemodynamic
changes in cerebral cor tex under
naturalistic conditions.
❸ Changes of hemoglobin concentration
in the prefrontal cortex.
The figure shows changes of
hemoglobin variables due to cognitive
processing (mathematical reasoning).
❹ Equivalent current dipole location of
motor fields during extension of the
right thumb (MEG study).
❺ Laboratory members.
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Recent Publications
Professor : Toshiko Futaki, Motomi Toichi,
Akira Mitani
Assistant
Professor : Hiroshi Sakai, Jun Matsubayashi
: See page 000-000
1. Tominaga, W., Matsubayashi, J., Deguchi, Y., Minami, C., Kinai, T., Nakamura, M., Nagamine,
T., Matsuhashi, M., Mima, T., Fukuyama, H., Mitani, A. (2009) A mirror reflection of a hand
modulates stimulus-induced 20-Hz activity. Neuroimage 46: 500-504.
2. Kinai, T., Matsubayashi, J., Minami, C., Tominaga, W., Nakamura, M., Nagamine, T., Matsuhashi,
M., Mima, T., Fukuyama, H., Mitani, A. (2009) Modulation of stimulus-induced 20-Hz activity
during lower extremity motor image. Neurosci Res 64: 335-337.
3. Sano, M., Futaki, T., Kobashi, R., Teranishi, K. (2006) Abnormal eye movement patterns on
a 2-point alternate fixation task and a routes finding task in unilateral spatial neglect. Jpn. J.
Occupational Therapy 25: 322-333.
4. Toichi M, Findling RL, Kubota Y, Calabrese, JR, Wiznitzer M, McNamara NK, Yamamoto K.
(2004) Hemodynamic differences in the activation of the prefrontal cortex: Attention vs. higher
cognitive processing. Neuropsychologia 42: 698-706.
5. Toichi M, Kamio Y, Okada T, Sakihama M, Youngstrom EA, Findling RL, Yamamoto K. (2002) A
lack of self-consciousness in autism. American Journal of Psychiatry 159: 1422-1424.
- Rehabilitation Sciences - Occupational Therapy
Brain Function and Rehabilitation
“Brain Function and Rehabilitation” is a new occupational therapy program established in Graduate School of Medicine, Human
Health Science Department in 2007. It is an academic program, the purpose of which is to bring together the knowledge and the
art regarding rehabilitation, from the view point of “interaction between human functioning and the environment”. We research
on the ways to support the persons with mental dysfunction and developmental disorders to control their lives and adjust to the
environment. As the basis of our research, we adopt medical and psychological assessment methods, such as motor function
assessment, mental processing assessment, and information regarding the relation between the disease and the disability.
Hiroshi Yamane, OTR, Ph.D.
Professor
In “Brain Function and Rehabilitation” program, we
carry out clinical research, education and clinical
guidance, regarding techniques and methodology
to facilitate rehabilitation and development of
the central nervous system. The subjects of our
practice are problems caused by functional or
organic dysfunction of the central nervous system
(including developmental disorders) such as mental
disorder, brain function disorder caused by brain
injury, and developmental disability. Our clinical
fields are hospitals, day care centers, rehabilitation
facilities, and schools. Let’s think, for instance, what
differences in the brain or the body makes a person
capable or incapable to imitate another person’s
movement? Occupational therapy in brain function
rehabilitation is a process of communication between
the person, the person’s body and the occupation.
We study the interaction between the brain, body
and the environment which occurs during carrying
out the occupation, and utilize the results for early
rehabilitation, supporting development, daily lives
and education of the disabled people.
Clinical research and education in mental function
field :
Our research and educational interests are the
occupational therapy, medical and social models of
disability, the acute occupational therapy system,
and supporting participation in the society, for
people with mental dysfunctions such as psychiatric
disorders, pervasive developmental disorders, and
higher brain dysfunction.
Clinical research and education in developmental
field :
Our research and educational interests are supporting
adjustment to the environment, occupational therapy
in educational settings, etc. The subjects of our
practice are children with developmental disorders
such as cerebral palsy, autism, learning disability,
attention deficit/hyperactivity disorder, Asperger
disorder.
Brain Function and Rehabilitation
Professor : Hiroshi Yamane
Associate
Professor : Toshihiro Kato
Instructor : New hire
Assistant
: Michiyo Uehara
: See page 000-000
Kyoto University
❶
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❶ Associate professor Kato: Presentation
❷ Clinical research of Sensory Integrative Intervention
❸ Development of Japanese version Sensory Integration Test
❹ NIRS measurement of brain function when acting
❺ Laboratory member
Recent Publications
1. Yamane H:History and current state of Japanese psychiatric occupational therapy. Journal of
Korean Association of Occupational Therapists:2010
2. 山根寛 : 心身統合の喪失と回復−コミュニケーションプロセスとしてみる作業療法の
治療機序 . 作業療法 ,27:73-82:2008
3. 山根寛 : コミュニケーションとしての作業・身体 , 作業療法 ,25: 393-400:2006
4. 山根寛 , 腰原菊恵 , 岩佐順子 : 急性期精神科作業療法の役割と課題−医学部附属病院精
神科神経科における試みより . 精神科救急 ,12:18-23:2009
5. Yamane H, Kinoshita T: An interactional model of mental disability based on the international
classification of functioning and disability (ICIDH-2). Asian Journal of Occupational Therapy,
1:1-11:2001
6. 加藤寿宏 , 山田孝 : 子どもは自分の運動能力をどのくらい正確に把握しているのか？ . 作
業療法 29:73-82:2010
7. 加藤寿宏 , 山田孝：現在の子どもの人物画−日本版ミラー幼児発達スクリーニング検査お
よびグッドイナフ人物画検査の標準化データとの比較検討− . 作業療法 29:743-753:2010
8. 第十麻紀 , 小林圭 , 加藤寿宏 , 新井紀子 , 松島佳苗 : 通常の学級における特別支援教育を
必要とする児童への作業療法の効果 . 作業療法 ,28:510-515:2009
9. 加藤寿宏 : 発達障害における連携と工夫−子どもを支える家族との連携− . 臨床作業療法
5:214-218:2008
- Fusion Unit for Near Future Human Health Sciences
Innovation Unit for Near Future System and
Technology
In this unit we study about the construction of practical medical system, machinery development, various patient management
based on social needs, medical needs, patient needs which will be done by uniting the knowledge of nursing/laboratory
medicine/physical-occupational therapy courses as well as utilizing medicine-mechanic cooperation and product government
college cooperation. Through the research and education in this unit we will bring up the health professionals who have wide
knowledge of human health science, provide appropriate information to society, propose at various clinical settings based on
their knowledge, and can show leadership in medical care teams.
Hidenori Arai
Professor
In this fusion unit we are trying to construct
medical care systems in which patients, elderly
or handicapped people can live in peace. For this
purpose we try to conduct interdisciplinary studies
through the interaction of nursing, laboratory
medicine, physical/occupational therapy courses,
where we can sometimes utilize medicine-mechanic
cooperation and product government college
cooperation.
Our research themes are the following:
1. To build a new health care system in an aged
society
2. To establish how to prevent the decline of ADL
in frail elderly collaborated with comprehensive
support centers in the community
3. Research on the effect of discharge planning
on QOL of a patient and their family and on the
education tools for medical staffs collaborated
with Department of Community Network and
Collaborative Medicine, Kyoto University Hospital
4. Effect of comprehensive geriatric assessment
(CGA) during hospitalization on ADL and QOL after
discharge
Through these research projects we are also aiming
to bring up various kinds of outstanding health
professionals who can develop leading-edge medical
technology, promote a new research field, participate
in policy making for health care, and play a role as a
super coordinator showing leadership among health
professionals.
Recent Publications
Innovation Unit for Near Future System and
Technology
Professor : Hidenori Arai
Associate
Professor : Kouichi Ishizu
: See page 000-000
1. Yamada M, Aoyama T, Arai H, Nagai K, Tanaka B, Uemura K, Mori S, Ichihashi N, Dual-task walk
is a reliable predictor of falls in robust elderly adults. J Am Geriatr Soc 59: 143-164, 2011
2. Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, Mabuchi H, Teramoto T, Sasaki
J, Nakaya N, Itakura H, Ishikawa Y, Ouchi Y, Horibe H, and Kita T. Prevalence of the Metabolic
Syndrome in elderly and middle-aged Japanese. J Clin Geriat Gerontol, 1: 42-47, 2010
3. Arai H, Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura
K, Saito S, Yamaguchi T, Daida H, Matsuzaki M. More Intensive Lipid Lowering is associated with
Regression of Coronary Atherosclerosis in Diabetic Patients with Acute Coronary Syndrome -Subanalysis of JAPAN-ACS study- J Atheroscler Thromb, 17: 1096-1107, 2010.
4. Miyake KK, Nakamoto Y, Mikami Y, Ishizu K, Saga T, Higashi T, Togashi K. F-18 FDG PET of
foreign body granuloma: pathologic correlation with imaging features in 3 cases. Clin Nucl Med.
35: 853-7, 2010.
5. Suga T, Nakamoto Y, Saga T, Higashi T, Hara T, Ishizu K, Nishizawa H, Togashi K. Prevalence of
positive FDG-PET findings in patients with high CEA levels. Ann Nucl Med. 24:433-9, 2010.
List for Tel, Fax & E-Mail – Human Health Science –
Department
Contacts
Environmental Health
Nursing
Professor : Sawako Suga, C.C.P., Ph.D.
TEL&FAX: +81-75-751-3961 e-mail: [email protected]
Associate Professor : Tomoko Wakamura, R.N., P.H.N., Ph.D.
Assistant Professor : Kazuyo Suzuki, R.N., P.H.N., M.A.
Human Body Defense
& Patho-physiology
Nursing Science
Professor : Yumi Saito
Professor : Shinichi Nomoto
TEL: +81-75-751-3919 e-mail: [email protected]
Assistant Professor : Momoe Utsumi
Nursing Science for
Lifestyle-Related
Diseases
Professor : Kiminori Hosoda
Associate Professor : Ikumi Honda
Associate Professor : Hiromi Sakuda
Assistant Professor : Sayaka Takenouchi
Psychiatric Nursing
Professor : Shigeru Sakuraba
Assistant Professor : Nami Konishi
Associate Professor : Chiharu Akazawa
Teaching Associate : Risa Fukuda
Child Health and
Development
Nursing
Professor : Machiko Suzuki
http://www.hs.med.kyoto-u.ac.jp/childcare/
Assistant Professor : Kanako Kiyokawa
Midwifery &
Women’s Health
Professor : Kiyoko Kabeyama
Associate Professor : Keiko Yagi
Assistant Professor : Yoko Chiba
Female Life-Cycle
Nursing
Professor : Nobuhiko Suganuma
Associate Professor : Hatsumi Taniguchi
Assistant Professor : Kotomi Yamaguchi
Preventive Nursing
Professor : Toshiki Katsura , R.P.H.N. , R.N. , Ph.D.
TEL: +81-75-751-3941 FAX: +81-75-751-3909
e-mail: [email protected]
Senior Lecturer : Mika Okura
Assistant Professor : Kanae Usui , R.P.H.N. , R.N. , M.N.Sc.
TEL: +81-75-751-3927 FAX: +81-75-751-3909
Home Healthcare
Nursing
Professor : Ayae Kinoshita
Assistant Professor : Masakazu Kubota
Basic Laboratory
Science
Professor : Shogo Oka
TEL&FAX: +81-75-751-3959 e-mail: shogo@@hs.med.kyoto-u.ac.jp
Professor : Kuniaki Saito
URL:http://www.hs.med.kyoto-u.ac.jp/saito-k/
Associate Professor : Masaki Ikemoto
Assistant Professor : Yasuko Yamamoto
Basic Nursing
Science
Nursing Science
Clinical Nursing
Science
Family Nursing
Science
Laboratory Science
Community
Health and
Community
Health Nursing
Medical
Laboratory
Science
Laboratory Science
Medical
Laboratory
Science
Department
Contacts
Innovational
Laboratory Medicine
Professor : Tetsuya Takakuwa
Associate Professor : Kentaro Ibuki
Applied Laboratory
Science
Professor : Souichi Adachi
Professor : Akihiko Nakaizumi
Professor : Masatoshi Fujita
Assistant Professor : Hiroshi Itoh
TEL: +81-75-751-3938 FAX: +81-75-751-3909
Medical Devices for
Diagnoses
Professor : Akitoshi Seiyama
Associate Professor : Satoshi Sasayama
Innovative Medical
Information
Imaging Technology
Technology and
Medical Engineering
Medical Imaging
System Sciences
Professor : Tsuyoshi Shiina
URL: http://www.hs.med.kyoto-u.ac.jp/shiina-lab/
Associate Professor : Kenichi Otsuka
TEL: +81-75-751-3942 FAX: +81-75-751-3909
Motor Function
Analysis
Professor : Hiroshi Kuroki, PT, PhD
Professor : Makoto Ishibashi
Senior Lecturer : Koji Ohata
Senior Lecturer : Yuko Maeda
Assistant Professor : Tome Ikezoe, PT, PhD
TEL: +81-75-751-3964 FAX: +81-75-751-3963
URL: http://www.hs.med.kyoto-u.ac.jp/ghs/research-domain/reha-science-aoms/index.html
Development and
Rehabilitation of
Motor Function
Professor : Noriaki Ichihashi
Professor : TadaoTsuboyama
Associate Professor : Tomoki Aoyama
Assistant Professor : Hiroshige Tateuchi
Assistant Professor: Minoru Yamada
Clinical Cognitive
Neuroscience
Professor : Toshiko Futaki
Professor : Motomi Toichi
Professor : Akira Mitani
Assistant Professor : Hiroshi Sakai
Assistant Professor : Jun Matsubayashi
Brain Function and
Rehabilitation
Professor : Hiroshi Yamane
Associate Professor : Toshihiro Kato
TEL: +81-75-751-3819 FAX: +81-75-751-3909
Physical Therapy,
Rehabilitation
Sciences
Fusion Unit for
Near Future
Human Health
Sciences
Occupational
Therapy
Innovation Unit for Near Future System
and Technology
Professor : Naozo Sugimoto
Assistant Professor : Tomohiro Ueno
TEL: +81-75-751-3938 FAX: +81-75-751-3909
Kyoto University
Professor : Hidenori Arai
Associate Professor : Kouichi Ishizu
Access Guide
Kyoto University
Graduats School of Medicine Kyoto University
©2010 Graduate School of Medicine Kyoto University
Printed in Japan

Graduate School of Medicine Kyoto University 2011

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