BMEP Yearbook AY 2010/2011 (PDF 1.8Mb)

Transcription

DEDICATION
The IALS University Network
The IALS University Network can be seen as an interdisciplinary “think tank”. It is a forum addressing cutting-edge issues in
the Life Sciences, as well as a place for the production and analysis of ideas which can then be diffused by public
understanding. Finally, it is a network with a transdisciplinary approach generating a pool of experts.
The Life Sciences represent a cutting-edge interdisciplinary and multidisciplinary field, building a bridge between the natural
sciences and the humanities. This bridge is important regarding many aspects of Life Sciences research and education,
including innovations in food technology, new medical technology and treatment options, as well as biotechnology and gene
technology. These dimensions will change our personal and social lives fundamentally. We believe that the methods and results
of the Life Sciences deserve our special attention at this stage of global development.
The Life Sciences have the potential to open up new markets, areas of study and education opportunities. Developing and
managing human resources in this sector has to take place carefully and responsibly. The IALS is committed to the innovative
development of “skills for the future”, a requirement for development of the Life Sciences within a globalized world.
The IALS is an international network. Each member represents a further network (of universities, institutions, organizations),
making the IALS an international network of networks.
Building on a very successful history in the areas of education and cutting-edge initiatives and projects on emerging critical
issues, spanning almost 30 years, we are currently focusing on: Education and Training – Advanced Students and Young
Scientists; International Network of Experts – Critical Issues Issues in the Life Sciences.
Drawing on its international network of experts, the IALS is able to respond to new ideas, initiatives and proposals in the Life
Sciences. The IALS "think tank" responds to scientists, clinicians, government officials and industry. We seek to provide a
forum where multiple stakeholders can obtain research, consultation, technical assistance, training and evaluation.
This Yearbook is dedicated to everyone who works hard to make that forum a success.
Prof. Hilmar Stolte, M.D.
President IALS & BMEP
University Professor em., Medizinische Hochschule Hannover
Distinguished Professor, Charité Universitätsmedizin, Berlin
30 Years of BMEP
A celebration of learning, sharing and leading.
Medizinhistorisches Museum Charité, Berlin
December 10, 2010
“Since BMEP was founded in 1979 by Prof. John Boylan, MD, and Prof. Hilmar Stolte, MD, over 1,600 German and American
students, post-graduates, faculty members and scientific assistants have been placed at universities and scientific institutes on
both sides of the Atlantic. In addition to this transatlantic bridge, IALS/BMEP has developed initiatives in St. Petersburg,
Russia; Guangzhou, China; and Istanbul, Turkey.
Today, nearly half of BMEP alumni are in leadership positions in medicine, academia, business and governmental/nongovernmental organizations. Our mission is to continue to foster new generations of outstanding doctors and researchers on the
leading edge of transdisciplinary biomedical developments.”
Prof. Hilmar Stolte, MD, President IALS
IALS Development Committee
Prof. Hermann Haller, MD, Dean of Education, Medizinische Hochschule Hannover, spoke about…
…the difference between lifeless and vital structures, and the necessity of providing scope for creative thought. “BMEP is an
example of a structure full of vitality and creativity.”
Prof. Winston Langley, PhD, Provost University of Massachusetts presented…
…his vision of a holistic university which uses the educational framework to focus not only on specialist knowledge and
personal development, but also
on relevant social and spiritual issues.
Ulrich Grothus, Vice Secretary General,
Deutscher Akademischer Austauschdienst, Bonn, certified…
…BMEP as achieving a high standard
BMEP will continue to be a success
within the DAAD internal quality control system. “I wish that
for many years to come.”
Prof. John Forrest, MD, Yale University School of Medicine and Director em. MDIBL, recounted…
…the beginnings of BMEP on Mount Desert Island. He spoke about the high level of commitment and high quality of the
“fellows”, committing himself once more to increasing promotion of mentoring as an important element of university
education.
There followed a panel session on "Careers - From Medicine to Biomedical and Life Sciences. Why are you here?" The
participants in the round table discussions were all participants of the BMEP program between 1985 and 2008.
Prof. Heide Siggelkow, MD, Gastroenterology and Endocrinology, Universitätsmedizin Göttingen, related how…
…participation in the BMEP program was the motivation to start researching, and it completely reshaped her career plans.
“BMEP changed my life totally.”
All participants agreed univocally that the research elective in the USA or Germany influenced their careers tremendously. It
taught them how to handle and interpret publications and laid the foundations for choosing an academic path and heading their
own research groups. Exposure to research should preferably take place after the first two years, at the earliest when entering
the clinical division of medical school.
During their own periods of training, all the BMEP participants met personalities who greatly influenced them, either by
teaching them research or clinical skills, or by broadening their horizons and giving them new opportunities. Fruitful
discussions, coaching and questioning all helped the individuals to define those areas of the life sciences “where the heart
beats”. These are the ones most likely to produce the best skills.
The panel session produced the following ideas and solutions:
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“Networking is very important” and here BMEP provides outstanding opportunities which should be used more
frequently and more actively.
“The BMEP network has people in all positions and medical areas”, meaning that those returning from the program
have the chance of a good start within the research institutions of their home country.
“Mentorship is a duty for every professor”.
Mentorship needs to become a more integral part of teaching, as foreseen extra time and not just on the fringes.
Research requires the space to be able to think creatively.
Jazzissimo Quartet from East-Westphalia
A second panel session addressed the topic of “Bologna: strengthening the relationship of medicine within life sciences”.
The experts presented various models of how the new (Bachelors, Masters) qualifications could become compatible with the
study of medicine. The basic question for discussion was how to link research and medicine, and how the process of European
conformity can reasonably be achieved. Which qualifications will the “2018” generation need, and would a German “go-italone” approach even be feasible?
There was lively participation in this discussion from the auditorium. The pros and cons of whether Bachelors/Masters degrees
really promote mobility were discussed. Flexibility in tertiary education must not become detrimental to specialist training.
There should be a clear point at which students decide to specialize.
What exactly is a Bachelors in Biomedicine? How can this title be filled with valuable content? Methods of accessing
knowledge need to be taught, rather than simply stuffing heads with more and more knowledge.
Is there any room at all within a “school-like” medical degree with a tight time frame for extended periods abroad? Are
students supervised sufficiently and appropriately? Mentoring was described as a necessity. Teaching staff need not only
adequate time for this, but also certain skills.
This panel session, moderated by Prof. Andreas Guse, Hamburg, produced the following ideas and solutions:
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Attaching increased importance to teaching, with teaching skills being taught to university lecturers as a matter of
course.
Imparting of meta-knowledge (e.g. accessing techniques).
Defining EHEA (European High Education Area) as the target area.
Achieving transparency for qualifications (what does each qualification mean, what do people with this qualification
know, what can they do?).
Making life and health sciences more flexible and better linked in order to improve education and promote exchange
in the teaching process.
Establishing mentoring as an integral part of the education process.
Providing sensible choices (choice itself is not a quality criterion).
Achieving a broader medical education.
“Bologna: Strengthening the Relationship of Medicine within Life Sciences
Justin Byrne, M.D. (BMEP alumnus)
& Joe Byrne, Ph.D., Provost em.
Tufts University, Boston
Professors Heide Siggelkow, Carsten Reinhöfer, Claudia Barth (BMEP alumni)
Participants
Forum I Hannover, April 2010
Name
Home University
Host University
Fadi Al-Saiegh
Medizinische Hochschule Hannover
Mayo Clinic, Rochester, MN
Felix Paul Bernhard
Universität Tübingen
Harvard Medical School, Boston, MA
Susanne Bethge*
Hochschule Neubrandenburg
Duke University, Durham, NC
Cheng-Ying Chiu
Charité Universitätsmedizin Berlin
Theresa Hartung
Mayo Clinic, Rochester, MN
Judith Kasper
RWTH Aachen
University of Maastricht
Thomas Daniel Kraemer
Justus-Liebig-Universität, Gießen
Ramona Krause
University of British Columbia,
Vancouver, BC
Katja-Theres Marquardt
Northwestern University, Chicago, IL
Kay Neumann
Universität Göttingen
Rush University, Chicago, IL
Moritz Osterholt
Universität Leipzig
University of Texas, Houston, TX
Florence Charlotte Pache
Rheinische Friedrich-WilhelmsUniversität Bonn
University of Michigan, Ann Arbor, MI
Patricia Elizabeth Palten*
Cornell Medical College of
Cornell University, NY
Hannes Ranke
University of Toronto, Toronto, Canada
Tom Roeschel
Oregon Health & Science University,
Portland, OR
Norman Frederik Rußkamp
Universität Erlangen
University of Michigan Health Systems,
Ann Arbor, MI
Bastian Oliver Sabel
Universität Rostock
Laura Katharina Schenk
Universität Münster
N.I.H. Bethesda, MD
Saskia Seidel
University of Southern California,
Los Angeles, CA
Kirill Solovyov*
RAMS St. Petersburg
Bianying Song*
TU Braunschweig
Vanderbilt University, Nashville, TN
Tim Ullrich
Universität Göttingen
Vanderbilt University, Nashville, TN
Alexander Vogt
Universität Rostock
The Rockefeller University, New York, NY
Yin Yu
RWTH Aachen
* postgraduate
Forum II Boston, April 2011
FADI AL-SAIEGH
Email: [email protected]
Home Institution:
Hanover Medical School, Hanover, Germany
Host Institution:
Mayo Clinic, Rochester, MN, USA
Research Mentor:
Andreas S. Beutler, M.D.
Assistant Professor of Medical Oncology and Anesthesiology
Personal Reactions to the US Experience:
Doctoral thesis research has always been my goal, especially because I am a
medical student in Germany, where a doctorate degree is only granted after
completion of a scientific project. Conducting research abroad only appeared to
me as an opportunity after my first research experience in Massachusetts, USA.
The Mayo Clinic in Rochester offers a great environment for working, studying and living. Rochester is a city of a hundred
thousand and almost everyone is somehow affiliated to the Mayo Clinic. Hence people are friendly, polite and help out new
students readily. Also, you will encounter people from all countries in the world and thus will most likely come into contact
with many different cuisines and special dishes. However, Rochester is not exactly the typical US city one would expect.
Having Chicago around the corner though, the very first opportunity can be seized to explore the ‘Windy City’. Most
characteristic of Minnesota are probably the harsh winters and snowstorms that we had plenty of during my stay. In fact,
Minnesotans already start warning newcomers about the cold winter in August, offering useful survival advice!
I consider myself fortunate to be part of such a prestigious institution and an innovative laboratory that focuses on pain research
and molecular neuroscience. As a new lab member, one will be guided by the PI and senior lab people as well. At the same
time, initiative and endurance is expected and highly appreciated!
Greatest Difficulties Encountered:
It was not very easy to find a good place to live in downtown right away. But after a couple weeks of e-mailing I was able to
find a roommate and a centrally located and clean apartment.
Most Humorous Incident:
I cannot think of a particular incident. However, I enjoyed many good and funny moments inside and outside the lab with all
the lab members.
Helpful Hints for Future Students:
-Look for a nice roommate to get in touch with people outside the lab quickly
-Get a credit card and a driver’s license (even if you have to take tests) that you can use as an ID instead of your passport
-Work very hard and travel a lot to get to see as much of the US as possible. You will notice great differences within the US!
Abstract on Research Topic – Fadi Al-Saiegh
Title: Transcriptome Profiling in Chronic Pain through the use of RNA-seq
Authors: Fadi Al-Saiegh1 and Andreas S. Beutler, M.D.
Institution: Mayo Clinic, Rochester, MN
Introduction:
Chronic pain is a common neurological disorder that is not easily manageable with currently available treatments. Patients
suffering from chronic pain do not necessarily show morphologic correlates, i.e. nerve lesions are not always present, which is
the reason why chronic pain is poorly understood. Molecular mechanisms may therefore be responsible for complex pain
phenotypes. These mechanisms include alterations in neuronal circuits and disinhibition of synaptic transmission, among
others. Recently, another culprit responsible for chronic pain was identified – alterations in the transcriptome of diseased tissue
(Hammer et al., 2010). The transcriptome is a term referring to the totality of RNA molecules in a given cell or tissue. Changes
in the transcriptome include altered gene expression levels, shifts in splice junction sites, and many others. RNA-seq has
evolved as powerful tool to detect such transcriptome modifications at a single base-pair resolution.
Using RNA-seq in dorsal root ganglia of allodynic rats can help with understanding complex pain phenotypes better and
potentially facilitate the development of new therapeutic approaches towards a disease-targeted strategy.
Materials and Methods:
Brown Norway rats undergo surgery, whereby the L5 spinal nerve is ligated and transected to evoke allodynia in these rats
(Kim & Chung, 1992). Behavioral tests are used to confirm allodynia. Successfully operated rats respond to a mechanical nonnoxious stimulus at a lower threshold than control rats. Two weeks after surgery, dorsal root ganglia (DRG) from allodynic and
control animals are harvested and total RNA is isolated. A cDNA library for RNA-seq is prepared following Illumina’s TruSeq
protocols and the library is eventually sequenced on a HiSeq 2000 sequencing instrument.
The resulting data represent reads from one preferred RNA class that is then analyzed using powerful computational
algorithms.
Results/ Conclusions: The work being performed by Fadi Al-Saiegh will not be completed for several more months, so no
conclusions can be drawn at the time of writing.
Note: Fadi Al-Saiegh received funding for his BMEP time in the U.S. from Mayo Clinic in Rochester, MN and DAAD.
FELIX PAUL BERNHARD
Home Institution:
Eberhard-Karls University, Tuebingen
Host Institution:
Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology
Harvard University, Boston, MA
Research Mentors:
Richard Schäfer, M.D., Universität Tübingen
Prof. Doug Melton, Laurence Dahéron, Ph.D., Ips Core Facility, HSCI
Steve Han, M.D., Ph.D., Massachusetts General Hospital, Department of Neurology
Prof. Kevin Eggan
Personal Reaction to the U.S. Experience:
Nine months seems like a reasonable amount of time to go abroad. However, I never felt time pass as fast as this before.
“The American” cliché may be different in the Boston-Cambridge-New-England area from sterotypes about “the species” in the
“rest of the country” in general, caused by Cambridge`s higher density of educational institutions, high schools, universities
and other schools than the rest of the country. The average member of the population is very well educated and extremely
friendly to foreigners. A very positive side-effect is a lively social and cultural life in Boston/Cambridge. Donations to art and
music seem to be an unwritten “social responsibility” for Bostonians: this assures a high level of cultural life, which can be seen
or heard for free or for an affordable amount of money in the City and areas near the Charles River, which separates Cambridge
from Boston. (Tip for cheap concert tickets: Holyoke Centre Postbox office with Harvard ID).
My nine months in Cambridge gave me lasting experiences both in the scientific world and in my social environment. I got a
lot of support and learned a lot from my mentors and colleagues in my lab, and formed new friendships in many different fields,
in laboratories, with people from the BMEP program, and in other places. I met people who made this time incomparable. I can
only encourage every M.D. student to go abroad and gain these valuable experiences!
My biggest difficulty was actually in Germany, where my visa was delayed and my departure endangered. My visa literally
arrived two hours before my plane was supposed to leave. Thanks to my knowledge of the postman’s route and great friends
who drove me to the airport, I caught my flight. After getting to the airport on time and sitting on the plane, we were then
unable to start because of machine damage. Afterwards, we again had troubles with clearance for take-off. In NYC I was not
allowed to enter because a Chinese citizen entered ahead of me with the same passport number as mine. After convincing the
immigration officer that I was not from China, and that I was not trying to share my passport with a Chinese citizen, he excused
the circumstance, which apparently happens statistically in fewer than one in five million cases. But I finally entered the US.
There were many funny incidents. Here is one of them. I used to take my showers for the first week after my arrival with cold
water because I didn’t understand the American system, which is different from the German one of switching cold and warm
water at the shower panel. I was impressed, thinking that Americans used only cold water for their showers, due to their fitness.
This was rewarded with laughter from my American colleagues.
- be polite and friendly, even if you think you already are!
- look up your apartment via craigslist, but don’t trust the offers. NEVER transact money when you have not yet seen the
apartment. There are many cheats trying to rent non-existing apartments.
-use contact with previous BMEP students to ask where they stayed, or try couchsurfing while you ask people living in the city
for advice. Be prepared for the fact that flats are overpriced and often in an unacceptable condition, very shabby or dirty.
-food often seems unhealthy or inaffordable. However, there are lots of cheap and good places around Harvard Square, like
Felipé’s Buritos . On Fridays next to Haymarket Square there is a farmer`s market, cheap and good. Otherwise Trader`s Joe.
-get a bike : e.g. at craigslist, too. It is much more efficient than public transportation, and cheaper, too.
-if you have a Harvard ID and no bike, be aware that there is a 50% reduction on monthly T-tickets and even a Harvard shuttle
for free, which runs until 2:30 A.M. if you live close by the university!
If you have any questions, please feel free to contact me any time!
Abstract on Research Topic – Felix Bernhard
Title: Neurodifferentiation in iPSC-lines with reactivated retroviral transgenes
Authors: Felix Bernhard, Emilee Greco, Laurence Dahéron, Richard Schäfer
Institution: iPS-Core Facility, Harvard Stem Cell Institute, Cambridge, MA, USA
Introduction:
The generation of induced pluripotent stem cells (iPSCs) by reprogramming terminally differentiated cells has represented a
new area of stem cell research since its introduction by Yamanaka in 2006. After successful retroviral reprogramming of
fibroblasts into iPSC lines, the viral transgene is expected to be silenced. However, some lines still express the transgene in the
undifferentiated state or re-express the viral transgene after further differentiation. This raises the question of whether there is a
differentiation-triggered mechanism of transgene-reactivation in iPSCs.
By screening different lines, we wanted to investigate systematically if and how iPSCs reactivate the viral transgenes upon
ectodermal (neural) differentiation.
For reprogramming we used MIG-retroviruses encoding for Oct 4, Sox2, Klf4 and c-myc to transduce human dermal
fibroblasts.
3 weeks after transduction of the dermal fibroblasts, the iPSC colonies were identified and picked. Each colony was designated
as a distinct iPSC line and expanded.
We characterized the iPSC lines with PCR and immunohistochemistry to look for the expression of endogenous pluripotency
markers (Dnmt3b, hTERT, Nanog, Oct4, Rex1, Sox2, SSEA3, SSEA4 and TRA-1-60). To functionally asses the pluripotency,
we differentiated the iPSC lines by embryoid body (EB) formation and evaluated the expression of lineage-specific
differentiation markers (Albumin, AFP, Flk1, GATA2, NCAM, Pax6) by PCR. Additionally, DNA-fingerprinting and
karyotyping were performed.
After screening for expression of the viral transgenes by PCR, we selected iPSC lines that showed silencing of the viral
transgene after reprogramming followed by reactivation after non-directed differentiation into EBs. In order to analyze whether
the reactivation of the viral transgene was associated with ectodermal differentiation, we differentiated the iPSCs into neural
progenitor cells and stained them with NCAM and SOX1 antibodies. Furthermore, we evaluated the chronological coexpression of the viral transgenes and lineage specific genes upon ectodermal differentiation by qRT-PCR.
Results/ Conclusions:
We successfully generated iPSC lines from dermal fibroblasts using a retroviral system and showed that there is a silencing of
the viral transgenes during the pluripotent stem cell state for most of the lines generated.
The screening process of multiple undifferentiated iPSCs and randomly differentiated iPSCs (EB) revealed a surprisingly high
percentage (10%) of iPSC lines showing a reactivation of the viral transgenes upon non-directed differentiation. Based on these
observations, we are currently analyzing and quantifying the reactivation of the viral transgenes in various iPSC lines before
and after the directed differentiation into neural progenitor cells.
The high percentage of reactivation of the viral transgenes highlights the importance of establishing non-integrative and nonviral reprogramming systems.
Note: Felix Bernhard received funding for his BMEP time in the U.S. from BMEP/DAAD.
SUSANNE BETHGE
Home Institution: Hochschule Neubrandenburg
Host Institution: Duke Clinical Research Institute,
The Fuqua Business School, Duke University, Durham, North Carolina
Research Mentor: Prof. Dr. A. Mühlbacher, Harkness Fellow in Healthcare Policy and
Practice, Commonwealth Fund, Duke Clinical Research Institute, The Fuqua Business
School, Duke University
My time in the U.S. was just outstanding! I would never have believed how much personal
and professional experience I would gain. I am very thankful that BMEP and B.Braun made it possible for me to have this
once-in-a-lifetime experience. Furthermore, I would like to thank my brilliant mentors who gave me the chance to work in this
productive environment. The time flew by and every day brought something new, exciting and very often unexpected. I met
amazing people and had a wonderful time.
Duke Clinical Research Institute and Duke University are amazing places to be and offer many opportunities in all regards. The
campus is fascinating and the people, faculty and professors are very distinguished. To see the American way of life and the
American way of working is interesting and I will benefit from the things I learned for the rest of my life.
My personal conclusion – it has been the chance of a lifetime and the most amazing time I have had in my life so far.
It is always a challenge to get everything started when you are faced with so much bureaucracy, but in the end everything
worked out somehow. At work our greatest challenge was to get IRB approval for the study, but with the great help of our
Institute we managed to work it out. (Thanks, Damon!)
There have been so many situations – I can’t really pick one. Most of the times the humorous incidents were related to language
“misunderstandings”. We still have to work out how to get around some language barriers. How could somebody from Europe
know that “mash” means “press”?!
Duke International House helped me with nearly everything. Get Skype and Facebook accounts and a Social Security Number,
they made my life much easier. I joined a volleyball team, which was the best way to get in contact with many others aside
from my colleagues and also allowed me to do some exercise. Perfect.
Abstract on Research Topic – Susanne Bethge
Title: Patient Priorities in Healthcare: Discrete Choice Experiments to Identify Patients’ Preferences
Authors: Prof. Dr. A. Mühlbacher, Susanne Bethge (M.Sc.)
Institution: Duke University, Duke Clinical Research Institute, The Fuqua Business School, Durham, North Carolina
Introduction:
Delivering efficient healthcare within limited budgets requires an understanding of patient priorities. Aligning clinical practice
and health policy with patients’ preferences will improve patient experience and might improve the effectiveness of health
interventions. Research is needed to provide decision-makers with a comprehensive assessment of patients’ priorities in the
relative value of healthcare.
The understanding of patients’ needs and expectations can lead to better compliance and adherence and therefore better
outcomes.
We conducted a discrete choice experiment (DCE) with chronically ill patients. The method allows the estimation of patients’
desire for different treatment features (preferences). Furthermore, the heterogeneity within preferences due to racial and ethnic
disparities, age or illness can be documented and considered in the design of innovative healthcare products or services. The
use of DCE to analyze patient preferences in healthcare is a novel feature of effectiveness studies. The aim of our research was
to analyze how DCE can be used to generate valid information for the provision of patient-centered health interventions and to
set up an appropriate model.
Healthcare research needs to be patient-centered and not merely focused on cost-containment. Preference data will help care
providers, policymakers and insurers to promote patient-centered care as the new standard of healthcare delivery. In this regard,
knowledge about the value of patients’ preferences in relation to drugs, healthcare supply or new forms of healthcare plans
could promote the emerging idea of patient-centered and high-performing healthcare delivery. In the forefront, however, it will
help to improve healthcare within limited budgets.
Note: Susanne Bethge received funding for her BMEP time in the U.S. from IALS/B.Braun, Melsungen. Axel. C. Mühlbacher,
Harkness Fellow in Healthcare Policy and Practice, received funding from the Commonwealth Fund (New York).
CHENG-YING CHIU
Home Institution: Charité Universitätsmedizin Berlin
Host Institution:
Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard
Medical School, Boston, MA
Research Mentor:
Prof. Jing X. Kang MD, PhD (Boston); PD Dr. med. Karsten-H. Weylandt PhD (Berlin)
Since this was my first stay in the US, I wasn’t sure what to expect. But when I finally got
here after a long visa application process, I was simply overwhelmed! Boston is one of the
most charming cities that I have ever encountered, small enough to get around easily on foot or by bike, but still full of
diversity, from Chinatown with incredible food, to Little Italy with its characteristic little restaurants and cafés, to the South
End with its old red brick houses. Boston Common is a wonderful place to linger while listening to open-air jazz concerts in the
spring and summer. Divided by the Charles River, Boston and Cambridge are not only the home of Harvard, MIT,
Northeastern, BU and UMass but also around 100 other colleges. People from all over the world come together to study and
research, providing a uniquely stimulating atmosphere. Never before had I met so many fascinating people at once, often
having conversations about the most random (but interesting!) things until late after midnight. Not least thanks to my lab team,
I was immediately integrated in the laboratory from the first day on and was able to extend my skills in research. Seize the
opportunity to attend lectures and seminars if you have some spare time from your lab, but also do not forget to enjoy this oncein-a-lifetime experience.
One of the difficulties that I encountered was the vast amount of paperwork that I had to complete in order to get my badge and
gain access to the research facilities, as well as an email address.
Generally, I had a laugh during my whole time in Boston! Many memorable night chats will stay in mind when German was
simply being translated to English directly; we came up with creative words and phrases such as “tigerduck” or “pi times
thumb”…
I also came across many confused faces when I explained that I was from Germany, but was immediately identified as being
German by a German because of carrying a signature Jack Wolfskin backpack.
-Start your visa application as early as possible.
-Use www.craigslist.com if you’re looking for a flat, bike, etc.
-If you have the chance, stay at a friend’s house upon arrival and go flat hunting on the spot. The pictures on craigslist.com
never look very realistic.
-Open up a Deutsche Bank account for free ATM use at any Bank of America. Get an American checking account to pay the
rent.
-Go to the many student pubs in Cambridge (i.e. Queen’s Head, Charlie’s Kitchen, Grendel’s Den, Muddy Charles Pub) for
cheap good food and drinks and enjoy the atmosphere.
Abstract on Research Topic –
Title: Suppressed liver tumorigenesis in fat-1 mice with elevated omega-3 fatty acids is associated with increased omega-3
derived lipid mediators and reduced TNF-α
Author: Cheng-Ying Chiu
Institution: Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard Medical School,
Boston, Massachusetts, USA
Introduction:
Liver tumors, particularly hepatocellular carcinoma (HCC), are a major cause of morbidity and mortality worldwide. The
development of HCC is mostly associated with chronic inflammatory liver disease of various etiologies. Previous studies have
shown that omega-3 (n-3) polyunsaturated fatty acids (PUFA) dampen inflammation in the liver and decrease formation of
TNF-α.
In this study, we used the fat-1 transgenic mouse model, which endogenously forms n-3 PUFA from n-6 PUFA, to determine
the effect of an increased n-3 PUFA tissue status on tumor formation in the diethylnitrosamine (DEN) induced liver tumor
model. Our results showed a decrease in tumor formation, in terms of size and number, in fat-1 mice compared to wild-type
(wt) littermates. Plasma TNF-α levels and liver COX-2 expression were markedly lower in fat-1 mice. Furthermore, there was a
decreased fibrotic activity in the livers of fat-1 mice. Lipidomics analyses of lipid mediators revealed significantly increased
levels of the n-3 PUFA-derived 18-hydroxyeicosapentaenoic acid (18-HEPE) and 17-hydroxydocosahexaenoic acid (17HDHA) in the livers of fat-1 animals treated with diethylnitrosamine. In vitro experiments showed that 18-HEPE and 17HDHA could effectively suppress LPS-triggered TNF-α formation in a murine macrophage cell line.
Results:
The results of this study provide evidence that an increased tissue status of n-3 PUFA suppresses liver tumorigenesis, likely
through inhibiting liver inflammation. The findings also point to a potential anti-cancer role for the n-3 PUFA-derived lipid
mediators 18-HEPE and 17-HDHA, which can down-regulate the important pro-inflammatory and pro-proliferative factor
TNF-α.
Note: Cheng-Ying Chiu received partial funding for her BMEP time in the U.S. from DAAD.
THERESA HARTUNG
Home Institution: Medizinische Hochschule Hannover
Host Institution: Mayo Clinic Rochester, MN
Research Mentor: Andreas S. Beutler, M.D.
Rochester, Minnesota is a small and peaceful town in the middle of nowhere,
surrounded by cornfields and farms. My first impression was that this must be one
of the main reasons why the Mayo Clinic became so famous. People working here
are less distracted. However, after a few months and after getting to know some
of the very friendly locals one will discover the, for Germans, unusual activities which are typical for the Midwest. In the
winter people go ice fishing, snow shoeing, dog sledding and drive their snowmobiles, and in the summer people go fishing,
canoeing, hunting and drive their four-wheelers. I tried a few of these activities and have to admit it is a lot of fun.
Most of life in Rochester takes place in and around the Mayo Clinic. The Mayo Clinic is an impressive institution with over
40,000 people working here from all over the world. Therefore this small town is more international than one would expect for
a town in the Midwest. It has been very interesting to interact with people of so many different nationalities, and I made some
very good friends.
Even though not all my experiments worked out perfectly right away, I had the chance to learn many different techniques and I
was greatly supported by the team of the Advanced Genomics Technology Center (AGTC), especially by Rod Feddersen. I
acquired a lot of new knowledge on Epigenetics and how data is analyzed. Thanks to my mentor, Dr. Beutler, I gained great
insight in scientific writing and the process of publishing.
Having to learn that research is not as straightforward as one might expect, but that one’s frustration threshold will increase
accordingly over time.
One day in December when I came out of the lab it had snowed pretty heavily, but I got into the car to go grocery shopping. On
my way I got suspicious. I was the only one on the street. When I reached the store, the four employees still there laughed at
me. We were having the second worst blizzard ever. That is what happens if you don’t have a TV and don’t watch local news.
If you are in Minnesota through the winter, try to drive up north and go dog sledding in Ely. It was an amazing experience to
mush your own sled over frozen lakes. I can highly recommend Wintergreen Lodge!
If you buy a car, buy a shovel! I got stuck in the snow during one of the worst blizzards, even with 4-wheel drive, and I had to
shovel my car out of the snow several times. In general a car is very useful in Rochester, because Chicago is a five-hour drive
and Minneapolis a 1.5 hour drive.
If you miss German dark bread and if it happens to be September, drive to Aldi and buy all the German dark bread they have
because they only sell it two months a year. I unfortunately got this information when it was too late.
If possible, contact students who have been in the lab before.
Therefore, please feel free to contact me!
Abstract on Research Topic – Theresa Hartung
Title: Epigenetic Mechanisms of Chronic Pain and DNA Methylation Profiling in the Peripheral Nervous System
Author: Theresa Hartung
Institution: Department of Oncology, Mayo Clinic, Rochester MN, USA
Introduction:
Chronic pain is one of the most common problems in clinical medicine. The underlying molecular mechanism still remains
unknown. Here we claim that epigenetic alterations in DNA methylation define a gene expression pattern characteristic for
chronic pain. DNA methylation is an epigenetic mechanism occurring mainly at the so-called CpG-motive and is well known to
regulate gene expression especially when taking place at the promoter of genes. Therefore, understanding how DNA
methylation is correlated with gene expression in the peripheral nervous system could be essential for explaining the process of
chronic pain and could be an alternative future therapeutic approach. The main goals of this study are to assay DNA
methylation in the dorsal root ganglion of the Brown Norway control rat and to compare these results with findings in the
chronic pain induced rat. Additionally, we will try to assay DNA methylation in different subpopulations of cells of the dorsal
root ganglion.
We established a spinal nerve ligation pain model in the Brown Norway rat, validated the operation by behavioral testing,
harvested the L4 and L5 dorsal root ganglion and then transferred this tissue to methylation and gene expression analysis. In
detail, we analyzed DNA methylation patterns in the peripheral nervous system of the rat by applying a single base resolution
method named Reduced Representative Bisulfite Sequencing (RRBS). This method combines isolation of DNA, digestion with
the restriction enzyme MspI, size selection, bisulfite treatment, amplification and last, but not least, DNA sequencing.
Results:
Methylation and transcription analysis of the dorsal root ganglion of the control rat have shown an inverse relationship between
DNA methylation and gene expression at the promoter region of genes. This correlation is consistent with results found in other
studies using different tissues and different models. Further results concerning the state of chronic pain and subpopulations of
cells are still pending.
Conclusions:
DNA methylation and gene expression at the promoter are inversely correlated in the dorsal root ganglion, demonstrating that
this epigenetic mechanism plays an important role in altering the transcriptome in the peripheral nervous system. Presumably,
DNA methylation plays an equally important role in altering the transcriptome of the state of chronic pain. This implies the
importance of further investigation.
Note: Theresa Hartung received funding for her BMEP time in the U.S. from the Mayo Foundation and DAAD.
SORA JUNG
Home Institution: Charite Universitaetsmedizin Berlin
Host Institution:
Dartmouth Medical School, Hanover, NH
Dartmouth – Hitchcock Medical Center, Lebanon, NH
Research Mentor:
Marc S. Ernstoff, M.D., Professor of Medicine
Dartmouth Medical School, Hanover, NH
I was so glad to have found the Ernstoff lab at Dartmouth. Prof. Marc
Ernstoff and his lab assistants, as well as Greg Tsongalis and Mary
Schwab, taught me more than I ever expected and made my stay an
effective and interesting experience. I was very impressed how easily
and quickly different labs collaborate and join forces without any
conditions or restrictions. The Dartmouth-Hitchcock Medical Center is
a great place to work.
Living in the U.S. without a car; expensive housing; this winter was the coldest and whitest in many years: -30ºC was not rare.
Crossing the Canadian border and back.
Do NOT forget your J1 paperwork (although your visa is in your passport) if you are planning to cross the border. Be prepared
for some personal questions. Don’t laugh. 
Abstract on Research Topic – Sora Jung
Title: Investigation of the BRAFV600E mutation in melanoma cell lines
Authors: Sora Jung, Marc S. Ernstoff, M.D.
Institution: Department of Medicine, Section of Hematology/Oncology, Dartmouth Hitchcock Medical Center, Lebanon, NH,
USA
Introduction:
Melanoma can be one of the deadliest cancers due to its high risk of spreading to distant organs and causing death. For tumor
cells to spread, they have to develop the necessary machinery which allows them to destroy the tissue matrix around them,
detach from their site of origin and burrow into the blood and lymphatic vessels. The most dominant machinery involved with
melanoma growth, invasion and spread is called BRAFV600E which is seen in 30-60% of all melanomas. BRAFV600E is a mutated
normal protein, which leaves the growth and invasion pathways used by melanoma in the “on” position. We speculate that
melanomas with BRAFV600E will have a different relationship with the host environment and thus different means by which to
invade and spread. The differences in cytokine production and antigen expression between BRAFV600E positive, BRAFV600E
negative and (BRAFWILDTYPE) melanomas were investigated in this project.
Materials and Methods: Twelve melanoma cell lines and a control dermal fibroblast line (human, adult) were propagated in
cell culture. DNA from these cell lines was prepared and analyzed for expression of BRAFV600E and other known mutations in
melanoma cells using PCR technology. At the same time, the cell lines were assessed for the production of several
cytokine/chemokines using Multiplex ELISA. Finally, employing fluorescent antibodies and FACS analysis the lines were
phenotyped for expression of melanoma related antigens during different phases of growth.
Results/ Conclusions: Differences in Cytokine/chemokine production were detected between BRAFV600E; BRAFWILDTYPE and
other known mutations. Differences in antigen expression could be seen between the cell lines and in different growth phases
within two cell lines. Further experiments and statistical analysis are ongoing.
Note: Sora Jung received funding for her BMEP time in the U.S. from the Konrad Adenauer Foundation.
THOMAS DANIEL KRAEMER
Home Institution: Justus-Liebig-Universität Gießen
Host Institution:
Mucosal Immunology at Brigham and Women's Hospital,
Research Mentor:
Richard S. Blumberg, M.D., Director, Gastroenterology Division
In terms of science, Boston is a real hotspot. Some of the world´s leading institutions and universities, like MIT and Harvard,
are located in Boston and the laboratories are full of smart and highly motivated scientists from all over the world. On my daily
journey to work I passed Dr. Murray´s Nobel Prize medal and walked through a hallway exhibiting portraits of the healers of
the century. Being in Boston and especially at Harvard was simply motivating, stimulating and a scientist´s dream come true.
However, Boston has more to offer then just science. In summer you can go on a whale watching tour, swim in the Atlantic
Ocean at Cape Cod, or get a cheap bus ticket and spend a weekend in New York. For sports fans, opportunities are almost as
numerous as the scientists. The New England Patriots in football, the Red Sox in baseball, and the Celtics in basketball
demonstrate sport at its best. I had the chance to see a Celtics´ game and I strongly recommend that you do that while you are in
Boston. I really enjoyed my stay in Boston and I´d like to thank my host tutor, Dr. Blumberg, my tutor in Germany, Prof.
Chakraborty, and the IALS for their great support.
Misspelling of my surname on my DS-2019 by the Harvard International Office resulted in me having to cancel my flight and
go to the USA embassy three times.
One research fellow didn´t like the color pink at all and refused working with any pink item. On Valentine´s Day the whole lab
was dressed in pink and we had a pink cake to overcome her dislike. I didn´t help.
Try to arrange your visa documents as soon as possible and don´t expect that this will be done automatically by BMEP,
especially when applying for Harvard.
Abstract on Research Topic – Thomas Daniel Kraemer
Title: Effects of the neonatal Fc receptor (FcRn) on albumin and IgG in the urinary and genital tract
Author: Thomas Kraemer
Institution: Department of Gastroenterology, Brigham and Women´s Hospital, Harvard Medical School, Boston,
Massachusetts, USA
Introduction:
FcRn is a MHCI related molecule and is expressed on epithelial and immune cells and binds albumin and IgG in a pH
dependent manner. Albumin and IgG are bound at acid pH (6.0) and relieved at neutral pH (7.4). The three major functions
mediated by FcRn are bidirectional transport, apical and basolateral recycling and protection from lysosomal degradation of
albumin and IgG. Over the last decade FcRn gained clinical importance in terms of drug delivery and half-life prolongation due
to its function. Today Fc and albumin conjugated drugs are successfully used in clinical applications.
In vitro: MDCK cells transfected with hAlbumin, hFcRn/beta2m and hAlbumin and hFcRn/beta2m, CellTrace™ CFSE Cell
Proliferation, Transwell®, bacteria internalization gentamicin assay, ELISA,
In vivo: FcRn KO and hFcRn transgenic BALB/C mice, i.p. and i.v. injection studies, urine collection from catheterized mice,
vaginal lavage.
hIgG is bidirectional transported in MDCK cells transfected with hFcRn/beta2m in a pH dependent manner. Mutations in the
Fc portion of hIgG with increased binding affinity at acid pH show increased transport from basolateral to apical. FcRn KO
BALB/c mice show decreased serum, urine and vaginal secretion levels of albumin and IgG compared to WT and hFcRn
transgenic mice. FcRn secrets IgG into the vaginal secretion and into the urine, presumably to provide immune surveillance.
Note: Thomas Daniel Kraemer received funding for his BMEP time in the U.S. from the DAAD.
RAMONA KRAUSS
Home Institution:
Host Institution:
Terry Fox Laboratory, Vancouver, BC, Canada
Research Mentor: Dr. Fumio Takei
Personal Reactions to the Canadian Experience:
I arrived in Vancouver after a 25-hour journey. On the way from the airport to my
apartment I just saw lights everywhere. Everything was so big compared to my
German hometown. I couldn’t see much of my neighborhood at night, and when I left
the house the next morning I found myself in a completely different world. I could
see very high buildings, mountains and the sea, all right next to each other. I was overwhelmed by these impressions.
The scenery is almost as diverse as the population of Vancouver. In Vancouver you meet people from all over the world. I have
never seen so many different cultures coming together anywhere else. It was a great experience to get to know so many
different ways of living and I am very happy that so many people introduced their cultures to me and let me be part of them. I
was sometimes skeptical and hesitant, especially when trying all the different kinds of food. But now I know how to eat with
chopsticks and that you have to make a noise when eating in a Japanese noodle house. I know how duck tongue, chicken feet,
jellyfish and bubble tea taste, and I love sushi. And next New Year’s Eve I will once again write my wishes on a piece of paper,
burn it and then drink the ashes with my champagne to make my wishes come true - just as I learned from my Iranian friends.
But I will not go swimming in the Pacific Ocean on New Year’s Day like Canadian people do. (It is supposed to help cure a
hangover.)
I met most of the people mentioned above at work. The people in the lab created a positive, friendly atmosphere. They worked
together and helped each other and I did not sense a strong hierarchy. My mentor Fumio gave me a warm welcome and made
me feel like part of the group from the start.
Although it was a great experience to get to know so many different cultures, I am a little bit disappointed that I did not get to
know the “typical” Canadian way of life, or what I had pictured it to be like. I did not meet many native Canadians in
Vancouver.
It was sometimes difficult to know how to behave in certain situations because people from different cultural backgrounds
show different reactions to a comment you make or behavior you show. Many people feel uncomfortable talking about their
private life and it was sometimes hard not to offend people.
I struggled a bit with the shallowness of the people. On the one hand it made it easier to get to know someone, but on the other
hand it was sometimes hard to distinguish between people who really cared about you and those who just wanted to have a
good time and did not remember you when you asked them for help.
My supervisor, Tim, asked me to get a B6 spleen as a control for FACS. We had fifty B6 mice. I took one of them and did not
see that it was marked. The next day Tim couldn’t find the B6 mouse into which he had injected sorted cells. There was only
one mouse that was marked and, with a chance of 1 to 50, I picked that one. Tim had to repeat his experiment. I felt very bad
and talked to another girl in my group about it. She laughed and said: “Don’t feel too bad about it. Someone else in our group
made the same mistake about a year ago. I guess Tim didn’t tell you that he took my mouse by accident and I had to repeat my
experiment.”
Be open to other cultures and do not be prejudiced. Accept every invitation and don’t be afraid to try new things. It will
broaden your horizons and your take on life.
Ask your mentor for help with your visa. The secretary of my mentor was a great help and made things so much easier.
Abstract on Research Topic – Ramona Krauss
Title: Lung Natural Helper cells are critical in asthma
Authors: Ramona Krauss and Tim Halim
Institution: Terry Fox Laboratory, Vancouver, BC
Introduction:
The lung immune system is important for protecting the body from infections with different kinds of pathogens. When
deregulated, however, a hyper-reaction of the immune system can cause immune diseases such as asthma. Asthma is a
heterogeneous disease. It can be caused by viruses, allergens or air pollution. Recent research results indicate that the onset of
the disease can also be induced by exercise or obesity. The course of the symptoms and the progress of the disease also differ
among patients. The classic model of asthma suggests that asthma symptoms are caused by TH2 cytokines like Interleukin-4, -5
and -13. In allergic asthma, allergens present on Dendritic Cells and activate CD4+ T helper cells of the adaptive immune
system to release these cytokines, which in turn induce the infiltration with other immune cells like eosinophils, macrophages
and neutrophils. IgE production and mucus secretion are also activated.
Today we know that not only TH2 cytokines, but also other factors and T cell subsets contribute to the onset and progression of
the disease, and that the innate immune system plays an important role, too. The classic model of asthma, which suggests that it
is a TH2 cell driven disease, is challenged by our finding that asthma symptoms can be induced by the intranasal administration
of the protease allergen Papain in recombinase activating gene-deficient (Rag-/-) mice which lack B-, and T-cells.
My group could identify a novel lymphocyte of the innate immune system, which produces large amounts of TH2 cytokines and
IL-17A. These cells were termed Lung Natural Helper (LNH) cells and are present in Rag1-/- mice, which lack T and B cells,
but not in Rag-/- Il2rg-/- mice, which are absent for all lymphocytes. In Rag-/- Il2rg-/- mice asthma could not be induced by the
administration of Papain. The reason for this is most likely due to the lack of LNH cells. This indicates that LNH cells play an
important role in asthma. The aim of my study was to characterize this novel cell type and its role in asthma in more detail.
Methods:
For the isolation of LNH cells, mouse lung cells were stained with antibodies binding to LNH-specific surface markers
(CD127, Sca-1, CD25 and CD117) and purified by FACS. To better mimic the natural environment of LNH cells, a lung
explant model was developed. C57BL/6 (B6), Rag1-/- and Rag-/- Il2rg-/- mice were sacrificed by CO2-asphyxation. Lungs were
instilled via 18G catheter with 1% agar in lung media (RPMI-1640, 10% FCS, 2-ME, P/S) at 37°C and cooled on ice. Lungs
were sliced into 0.5 mm section by razor and placed in 2 ml lung media. The lung explants were stimulated with different
cytokines, Papain or phorbol 12-myristate 13-acetate (PMA) and Ionomycin. After certain intervals, supernatants were taken.
Amounts of specific cytokines, produced by lung explants and released in the supernatant, were detected by sandwich ELISA.
To confirm that the main producers of these cytokines were LNH cells and not other lung explant cells, intracellular staining
was performed. Therefore, the Golgi Plug inhibitor Brefeldin A was added to the media. Brefeldin A prevents exocytosis and
cytokines produced in the cell are kept inside the cell and not secreted in the supernatant. Cells were stained for specific
cytokines and surface markers.
Results and Discussion:
Lung Natural Helper cells are lymphocytes, part of the innate immune system as they are present in Rag1-/- mice which lack an
adaptive immune system. These cells represent a notable population of lung lymphocytes that do not express lineage markers.
They can be characterized by the expression of stem cell antigen-1 (Sca-1), stem cell factor receptor CD117 (c-kit), IL-2Rα
(CD25) and IL-7Rα (CD127). The morphology of LNH cells resembles resting lymphocytes. Purified LNH cells are able to
produce large amounts of the TH2 -cytokines IL-3, -5 and -13 and moderate amounts of IL-4, IFNγ and IL-17A upon
stimulation with PMA and Ionomycin. Their phenotype and cytokine producing potential is similar to other innate lymphocates
that were recently discovered in the gut and in helminth infection. To find physiologic stimulants for LNH cells, purified LNH
cells were cultured with different cytokines. Cytokine production of LNH cells could not be induced by a single cytokine, only
by a combination of specific cytokines. The reason for this might be that important cytokine receptors were blocked by the
monoclonal antibodies used for the purification or that isolated LNH cells lack factors of their microenvironment, which are
important to induce cytokine production. To better mimic the physiologic environment of LNH cells, the lung explant model
was used. In this model IL-25 and a combination of IL-2 and IL-7 could induce IL-5 and IL-13 production by lung explants of
Rag1-/- mice and LPS could induce IL-17A production. Intracellular staining of lung explants confirmed that LNH cells were
the major producers of these cytokines. LNH cells represent an important source of TH2 cytokines and IL-17A, which mediate
asthma symptoms. Therefore, Lung Natural Helper cells represent a novel target for asthma therapy. The depletion or blocking
of LNH cells could lead to an improvement of asthma symptoms.
Note: Ramona Krauss received funding from DAAD (Deutscher Akademischer Auslandsdienst) and PHSA (Provincial Health
Service Authority) British Columbia for her time spent in Canada during the BMEP year.
Photos Krauss
Photos Ramona Krauss
KATJA-THERES MARQUARDT
Home Institution:
Host Institution:
Feinberg Cardiovascular Research Institute,
Feinberg Medical School, Northwestern University,
Chicago, IL
Research Mentor:
Jörn Tongers, M.D. and Douglas Losordo, M.D.
Personal Reactions to the U.S. Experience:
Chicago, the windy city, caught me from the first moment. Arriving in the
fall, it was still warm and nice out, and my work and sleep places were both near Lake Michigan.
My work was mainly done at the Downtown campus, where the medical and law school are also located. The proximity of
work and the Med School presents a great opportunity to see some lectures, classes and American medical students. Talking to
them and to other Chicago citizens, you will recognize that Chicago is THE melting pot. It is hard to find people originally
from Chicago. Almost everyone has spent at least some part of his life in different parts of US or the rest of the world. It is
nothing special to be a foreigner. There is also an opportunity to become a Chicagoer . There is a huge German community in
Chicago, and many have opened a “Brauhaus” or a bakery. My host research institute represents the international character of
the city. My colleagues did their university degree and/or post-doc in India, China, Russia or Canada.
Only steps away from the Loop there are several parks (with wonderful ice rinks in the winter and concerts in the summer),
Michigan Avenue, and a variety of museums, bars and restaurants. But be careful - the bouncers are hard! You have to be 21 to
be able to enter a bar, sometimes even restaurants or a club.
The whole Midwest is relatively flat, and the winter is cold and snowy (blizzard, -30°C.) Thanks to the amazing, wellorganized and talented ski team and the Salseros (salsa group) at Northwestern, I appreciated the cold and got through. A
highlight was definitely the week in Sun Valley, Idaho, for participation at College National Championships.
This sounds very general, but it is difficult to calculate how much money you will have and how much you must spend just on
living expenses because it is expensive in the cities, especially in Chicago. I already knew this in Germany, but did not have
much time to get organized. My tip: Discuss with your (host) university/mentor a small salary and further funding
opportunities, and look out for scholarships.
There have been a ton: An American, one of my ski teammates whom I was meeting for the first time, was costumed as a
German: old, red-flowered Hawaii shirt and very tight black leather leggings. He asked around what his costume represented,
and everyone there (all Americans) could tell him - except me.
Several times during the year I had to hear “You are the worst German ever”, due to my dislike of beer and because I had not
seen the movie “Beerfest”, where most Americans imagine that Germans are coming from. Furthermore, my adopted Chinese
lab sister, standing next to me and barely reaching to my chin, said: “Oh, my little sister.”
Chicago is a city to discover. You probably have some wishes for your BMEP time – here, you can realize them, as you can
find nearly everything – even skiing in the “flatland”, medical students with time to meet a German friend, and so on.
The visa was a risky game in my case – so start early and organize it YOURSELF! Deal with the DS2019 yourself. That
includes: calling your mentor (or his secretary), call the international office of the university and get everything you need for
your DS2019. If you have that – find someone who wants to wait 3 hours in front of the American embassy for you, or a place
to leave all your stuff. Everything else will be easy.
If you have any questions, feel free to ask me!
Abstract on Research Topic – Katja-Theres Marquardt
Title: Integration of the Hemeoxygenase-1 System into Fibrinogen-based hydrogels for Therapeutic Applications In Inschemic
Cardiovascular Disease
Authors: Katja-Th. Marquardt, Douglas W. Losordo, Jörn Tongers et al.
Institutions: Feinberg Cardiovasculare Research Institute, Feinberg School of Medicine, Northwestern University, Chicago
and Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
Introduction: Hemeoxgenase-1 (HO-1) is the regulated isoform of the heme degrading enzyme family. HO-1 is found to be
upregulated under various conditions of stress including ischemia and inflammation. Its byproducts are iron, biliverdin and
carbon monoxide, which have been shown to exert beneficial effects in various pathological states. Aiming at therapeutic
applications, it is necessary to develop a local and controlled delivery method of these. For this purpose tools have been
identified in the evolving field of biomaterials.
Materials and Methods: We integrated an HO-1 lentivirus into a fibrinogen-based hydrogel. The virus-hydrogel complex was
applied to endothelial cells (HUVECs) and fibroblasts (H1080s), as well as a diabetic (db/db) mouse wound healing model.
Further, we investigated the concentration and time-dependent release for hemeoxygenase lentivirus, as well as bilirubin. In
order to include carbon monoxide, we synthesized the carbon monoxide releasing molecule CORM-3 as previously described.
Briefly, the commercially available compound CORM-2 is mixed with glycine in methanol and stirred. After removal of
methanol, the product is dissolved in THF, filtered mixed with Petroleum ether. Then the liquid is removed under pressure.
Eventually purified in hexane and the final product verified with FT-IR. The product is a pale yellow powder. CORM-3 is
going to be administered the same way as described for bilirubin and the HO-1 lentivirus.
Results: We showed a time-dependent release of bilirubin and hemeoxygenase lentivirus. The release spikes at 24 to 48 hours
followed by a rapid decrease. A significant rest remains in the hydrogel until its full degradation. These hydrogels degrade over
8 to 12 days in vitro.
On the other hand, our hydrogels degrade faster in-vivo and cannot be seen after 7 to 8 days. From the translational point it is
relevant that the hydrogel does not induce any immune response as determined by histological HE, CD45 and CD68 stainings.
Based on RNA(RT-PCR) and protein expression (histology) is dose-dependent on days 3,7,10 after application. In ongoing
work, we are currently integrating CORM-3 into the hydrogel and measure CO release. Finally we are applying all these HO-1
carrying hydrogels to diabetic db/db mice in order to assess the beneficial effect on wound healing; pilot experiments show
promising trends.
Conclusions: We concluded a time-dependent release of hemeoxygenase-1 and its product bilirubin from a fibrinogen-based
hydrogel. The system seems to have beneficial effects in the diabetic wound healing model. Further evaluation, in ongoing
experiments, is needed.
Note: Katja-Theres Marquardt received funding from the DAAD for her BMEP year in the U.S.
KAY NEUMANN
Home Institution: Georg-August-Universität Göttingen
Host Institution: Rush-University, Chicago, IL
Research Mentor: Prof. Lothar Blatter, M.D., Professor of Medicine
I like the way Americans deal with each other in daily life. It is so friendly,
outgoing and uncomplicated, which makes it very easy for people to get
along with each other. Especially small talk is fun, and it is an easy way to
get to know the American mentality. On the other hand, I think it can be difficult to stay in touch with Americans.
I was overwhelmed by all the possibilities and diversity in Chicago. There are plenty of things to do and it is by far the most
beautiful city I have seen in the US.
I had a hard time at the beginning getting my apartment... It took a while, although I was supposed to get it as soon as possible.
Also, the winter in Chicago is cold and long and keeps people inside. So you had better go to Chicago in the summer.
Try to get in touch with students at your university. Try to see as much as possible and not only the well-known tourist places.
Rent a car and do a road- trip!
Prof. Robert Rich, Chairman of the Board IALS, and other Forum II participants
Abstract on Research Topic – Kay Neumann
Title: Influence of redox-dependent PKA and CaMKII regulation on cardiac Ca2+-cycling
Authors: Kay Neumann, Lars S. Maier, Lothar Blatter
Institution: Rush-University, Department of Molecular Biophysics and Physiology, Chicago, IL, United States of America
Introduction:
H2O2 dependent oxidation of the protein kinase A (PKA) regulatory subunit RI leads to disufide bond formation (Cys17/38)
which induces dissociation of the PKA holoenzyme complex. This PKA activation causes increased phosphorylation-levels of
phospholamban, phospholemnan and troponin (amongst others) and results in a positiv inotropic effect in isolated cardiac
myocytes (Brennan et al. 2006).
Furthermore, H2O2 dependent oxidation of Met-281/282 of the Ca2+/Calmodulin dependent protein kinase II (CaMKII) causes
Ca2+/Calmodulin independent activity (Erickson et al. 2008). CaMKII activation results in a positive inotropic effect too.
Moreover, both pathways are involved in the positive ionotropic effect of isoprenaline.
Isolation of single cardiac myocytes of rabbit/mouse hearts.
Confocal Ca2+ imaging with Fluo-4. Epifluorescence measurement of intracellular Ca2+ with Indo-1 and Fura-2. Sarcomere
length detection for contractility measurement of single cells. Single-channel recordings for measurement of a direct influence
of oxidative species on Ryanodine-Receptor properties.
Oxidative species such as H2O2 influence Ca2+-cycling of isolated cardiac myocytes acutely in a positiv ionotropic manner. It
results in increased Ca2+ transient amplitudes, accelerated Ca2+ reuptake (as measure of SERCA function), elevated diastolic
Ca2+ levels and increased contractility. This positive ionotropic effect seems to depend partly on redox-dependent PKA
activation.
On the other hand, there is also a direct effect of oxidative species on the open-probability (Po) of the Ryanodine-Receptor.
H2O2 increases Po and opening events in a dose-dependent manner independent of PKA and CaMKII activation.
Note: Kay Neumann received funding for his BMEP time in the U.S. from DAAD and received support from the “Leducq
Foundation Transatlantik Network of Excellence on Redox and Nitrosative Regulation of Cardiac Remodelling”.
MORITZ OSTERHOLT
Home Institution:
Medizinische Fakultät, Universität Leipzig
Host Institution:
The University of Texas Medical School at Houston,
Internal Medicine, Division of Cardiology
Research Mentor: Heinrich Taegtmeyer, M.D., Ph.D.
Tell somebody in Germany that out of 50 states in the USA you have chosen to go to Texas for one year and you will probably
get the same looks that I got: amazement mixed with pity, wishing you the best of luck, because you will need it.
Germans might be a bit biased against the Lone Star State, and admittedly so was I. But soon after my arrival I realized how
wrong I was, and a wonderful year began. Texans are very friendly and hospitable. And it is true what they say. Everything is
bigger in Texas: buildings, cars, and highways. My host institution is located in the middle of the Texas Medical Center, a huge
complex, consisting of almost 50 different hospitals and research institutions. Here you are among many excellent researchers
and clinicians, which may be a little intimidating at first, but I found it to be very motivating and inspiring.
Granted, Houston is not the most beautiful city in the U.S., and it takes quite a while to discover it. But after some weeks you
will come to know the small and beautiful places that Houston has to offer. And, with a variety of museums, parks and
concerts, as well as many excellent bars and restaurants, you will always find a place to go whenever you are not at the bench.
Greatest Difficulty Encountered:
The trip to the U.S. starts with a major hurdle: to get a DS-2019 for your visa application. However, in the end it is less a
question of whether or not you will get this form, but rather of when you will hold it in your hands. So it is best to start the
process as soon as possible.
Going shopping in Houston without a car is quite a challenge. This city is not designed for pedestrians: public transportation is
rudimentary and bus schedules give you no more than a rough estimate of when to expect the next bus (I have spent hours
waiting for buses to pick me up at the grocery store in the middle of the night).
The whole year was filled with funny situations and I had so much fun during my time in Houston. Going to work in the worst
Christmas shirt man has ever made is definitely one of the things I will never forget. It was a gift/joke from a friend in the lab
and I had to wear it. The reactions of people who saw me that day made us laugh even days later.
- Ask at MLP for insurance. They have good offers for medical students.
- Get used to the fact that German bureaucracy is not the worst in the world.
- If you are staying in Houston: go to the rodeo! You don’t have to be a cowboy to enjoy this event.
- Go and visit Texas. There’s more to it than you think.
- Open a bank account in the U.S.
Abstract on Research Topic – Moritz Osterholt
Title: Markers and Mediators of Autophagy Do Not Predict Adaptation or Maladaptation of the Heart in Two Murine Models
of Type 2 Diabetes Mellitus
Authors: Moritz Osterholt, Kari Wellnitz and Heinrich Taegtmeyer
Institution: The University of Texas Medical School at Houston, Division of Cardiology
Introduction:
The effects of Type 2 Diabetes (T2DM) on the heart include increased fuel supply and increased ROS production. Oxidative
stress results in the misfolding of proteins, which is considered a main cause for proteotoxicity and contractile dysfunction.
Autophagy is increasingly recognized as an important pathway for the degradation of damaged proteins and cell organelles. A
potent inhibitor of autophagy is mTOR. We speculated that with insulin resistance and reduced signaling along the PI3K/Aktpathway, mTOR may be less activated in type 2 diabetic hearts, thereby activating the autophagic pathway. We now tested the
hypothesis that autophagy is increased in type 2 diabetic hearts.
To learn whether the phenomenon can be generalized, we used two models for T2DM: the leptin receptor-deficient db/db
mouse and the RCS-10 mouse, in which polygenic interactions induce a diabetic phenotype, which substantially resembles the
phenotype of human T2DM. Both groups were compared to their individual control groups (C57BLKS/J or SWR/J mice,
respectively).
Results:
Both models showed increased blood glucose, insulin and triglyceride levels at 15 weeks of age. At the same time, after being
hyperglycemic for at least 3 weeks (non-fasting blood glucose > 250mg/dl), protein levels for the autophagic mediators Beclin1, Atg5-12-conjugate and LC3 were increased in both type 2 diabetes models (p<0.05; n=10). Unexpectedly, while it is already
known that hearts of db/db mice develop reduced fractional shortening and increased left-ventricular end-systolic diameter at
15 weeks of age, echocardiographic assessment of cardiac function revealed no changes in these parameters in hearts of RCS10 mice (n=4). Neither Akt, mTOR nor 4EBP1 show significant changes in phosphorylation in both models (n=4).
Conclusions:
In summary, autophagy is increased in the hearts of two different mouse models of type 2 diabetes, independent of their
functional status and independent of mTOR activity. We conclude that markers and mediators of autophagy do not predict
either adaptation or maladaptation in the heart in murine models of diabetes mellitus.
Note: Moritz Osterholt received partial funding from the DAAD for his BMEP time in the U.S.
Moritz Osterholt and other BMEP participants 2010/11
FLORENCE PACHE
Home Institution: Charité- Universitätsmedizin Berlin
Host Institution: Department of Pathology, Laboratory of Peter A. Ward M.D.,
The University of Michigan, Ann Arbor, MI, USA
Research Mentor: Peter A. Ward, M.D., Godfrey Stobbe Professor
So this mysterious Ann Arbor lymphoma classification was not named after a
woman after all?
This was the first revelation after applying to Michigan. There were many more
to follow: why sharing a house with 5 Americans is an irreplaceable experience;
why bread here does not have crusts and you can therefore trace the presence of
German customers in a supermarket by fingerprints on the fluffy loaves; why
living in a small college town is so convenient; what tailgating before football
games means to undergrads (those red cups really exist); what to expect when
ordering any food or drink in large; why Ann Arbor has this cute summer moving tradition that strongly reminds me of
“musical chairs”: everybody moves out in summer and has to find a place to squat for two weeks before the new lease starts in
another house.
Altogether I have had a fabulous time in the US.
It was my wish to cycle, even throughout the Michigan winter. This sometimes felt like an Antarctican expedition, but I
succeeded.
So far everything has been astonishingly smooth. Take the advice to start well in advance with preparations for your visa (the
SEVIS fee is not the non-immigrant visa application processing fee), to keep copies of everything (and not leave the passport or
any other document on the Xerox and then wondering for days or weeks were it has gone to…) or scanned versions on the PC.
With all the support from our wonderful GlobalReach center and pathology administrators, there were no major difficulties.
Before Christmas, Norman, a roommate and I took the plastic Christmas tree and decorations from the lab home with us. I also
wanted to bring home all the private things I had accumulated in the lab, as it was my start base for evening sport practice. So
the three of us squeezed into the elevator, fully equipped with tree, Christmas lights, running shoes, swimming stuff - just
imagine what a sight this was. Then my roommate suddenly burst out, “Fear not, I have badminton rackets!”
-Craigslist for housing, furniture, bikes and much more
-The Deutsche Bank/Bank of America/BNP Paribas (in case you ever open a French account)
- If you want to join a sports team, orchestra or choir, try-outs/ auditions are often held before the fall semester begins, so start
looking for your favorite distraction early.
- Ending up in winter in the mid-west does not mean perdition. Ice-skating, hockey or cross-country skiing are just some
options. Have you ever tried curling or broom-ball?
Abstract on Research Topic – Florence Pache
Title: Influence of C5a on macrophage derived IL-27 in sepsis
Author: Florence Pache
Institution: Department of Pathology, University of Michigan, Ann Arbor, MI, USA
Introduction:
Interleukin 27 (IL-27) is a newly discovered cytokine that belongs to the IL-12 cytokine family. Remarkably it displays a
unique immunoregulatory function in T cell development and exhibits both initiating and attenuating properties during immune
response.
Sepsis and systemic inflammatory response syndrome are severe medical conditions which can lead to multi-organ failure and
death. Extensive tissue damage can be caused by uncontrolled inflammation and infections must therefore be tightly controlled
and finely balanced by the immune system. The complement factor C5a, which acts as anaphylatoxin, is generated both in
human as well as experimental sepsis and possesses immunomodulatory properties on cells of the innate immune system.
Macrophages are monocyte-derived phagocytic cells and play a key role as a first line of immune defense. They have been
shown to express a huge variety of cytokines and the receptors for C5a, C5aR and C5L2, the latter being an orphan receptor.
The influence of C5a on IL-27 production is not yet known.
In order to assess the influence of C5a on macrophage derived IL-27 in sepsis we performed the rodent model of endotoxemia
by i.p. injection of lipopolysaccharide (LPS), 10mg/kg BW, in wildtype and C5aR deficient C57BL/6 mice. IL-27 protein
levels in plasma were measured by IL-27-ELISA, and induction of IL-27 mRNA in splenocytes was assessed by real-time PCR.
LPS stimulation of different primary mouse macrophages (peritoneal thioglycolate-elicited macrophages, bone-marrow derived
macrophages) as well as mouse macrophage cell lines (RAW246.7, MH-S) in presence and absence of C5a was performed- IL27 protein levels were evaluated by ELISA and IL-27 mRNA induction was analyzed.
To elucidate the source of IL-27 during sepsis endotoxemia experiments were performed after depletion of neutrophils, NKcells, splenocytes and macrophages.
Furthermore, characterization of different primary macrophages and macrophage cell lines was undertaken by co-staining for
macrophage-markers as well as C5aR and IL-27 by flow cytometry.
Blocking of C5aR signaling in vivo leads to a moderate upregulation of IL-27 on both mRNA and protein level, and in vitro
administration of C5a suppresses IL-27 production respectively. The sources of IL-27 during experimental sepsis are
macrophages which carry C5a receptor. These data support the regulatory role of C5a upon macrophage derived IL-27 in
sepsis.
Note: Florence Pache received funding from the German National Academic Foundation.
PATRICIA PALTEN
Home Institution:
Department of Obstetrics
Host Institution:
New York-Presbytarian/Weill Cornell Medical College of Cornell University,
Department of ObGyn/Division Maternal-Fetal Medicine
Research Mentors:
Prof. A. Grünebaum, MD FACOG, Prof. JW. Dudenhausen, MD
I am German-American. When I was a child, my family spent some summers in the US. So I had been there several times
before but had never lived there for a longer period of time and the American School I had attended for a few months was
located in Europe.
NY fascinated me right away and doing research at Weill Cornell Medical College was awesome! In the department I was
cordially received and it was great to work together with my supervisors Prof. Grünebaum and Prof. Dudenhausen (thank you
both so much!). I was able to participate in excellent seminars and lectures at the institution. My time at Weill Cornell and
meeting international experts in the field of ObGyn there reinforced my desire to work in academia, combining research and
clinical work. I want to emphazise that all this would not have been possible without the great support of the BMEP program
and of the IALS/ B. Braun-Melsungen Fellowship!!!
I could have easily stayed longer in NY because I enjoyed the cultural diversity of the people and the different rhythms I would
find everywhere in the city. The energy and the speed of NYC made me very happy and I loved the atmosphere of the
metropolis. Because of all the new influences I had a lot of energy myself. Soon though, I also developed a critical attitude
towards this consumer- oriented world! There were quite a few people who couldn’t cope very well with life in this glamorous
metropolis. And when I found out more about how the American health system worked, I was very happy about our health
insurance!
Before I could start work at the hospital I had to go for a medical check up (including a toxicological drug screening of my
urine etc!). When I developed bacterial bronchitis – it was late Friday afternoon - I needed a prescription for some antibiotics
and couldn’t reach my supervisor. So I went to the workforce healthcare service where my check up had been done and was
more than surprised when they refused to treat me although I had international health insurance. Instead I was told if I needed
to, I could go to 16th street to the Clinic for Uninsured. Of course things worked out fine when my supervisor took care of
things shortly later, but I got a slight impression of what it would feel like if medical treatment was refused.
There were many humorous incidents and I laughed a lot when I was out there. I recall some very funny incidents on the
subway…and… you will find that having been on the subway in NY makes you feel so much less embarrassed about some
aspects of your own behaviour - so just relax!
1.
2.
3.
4.
It is useful to get an American (!) gmail account. You can make calls all over the US for free then.
Although NY is expensive, there are a lot of things you can enjoy without money like free or very cheap concerts at
the Julliard School or the Carnegie Hall Concerts. You might be lucky and be given free tickets to go and see a
concert. This happened to me twice – once in the break I was given a $300 ticket for the first row in the MET – since
there were still 3.5 hrs to go, it was great!
For all the museums there are certain times where you do not have to pay to get in and quite a few of them are open to
donations, but be prepared - it can be very crowded!
Enjoy your stay and… explore the city! Get a monthly subway ticket. Enjoy the many excellent musicians and
different rhythms in the subway stations and the rhythms when you walk down the street. You should walk a lot
because that’s the way to get to know the city! And no worries, Manhattan is safe, even at night!
Abstract on Research Topics – Patricia Palten
I was involved in two different projects.
Title 1:
Obstetric Brachial Plexus Injury (review)
Title 2:
Plagiarism in medical articles
Author(s):
PE Palten, A Grunebaum, JW Dudenhausen
Institution: Department of ObGyn, Weill Cornell Medical College, NY, USA
1.
Introduction:
Obstetric brachial plexus injury (OBPI) is an injury of the plexus brachialis resulting in either permanent or transient
impairment of the newborn. (…) OBPI is most often the result of traction during the birth process. When an injury occurs it is
sometimes attributed to an intrauterine onset.
We were interested in assessing the extent of intrauterine BPI. We hypothesized firstly that BPI would occur rarely after c
section but almost exclusively after spontaneous vaginal delivery of the baby, and secondly that there would be a correlation
between permanent plexus injuries and vaginal deliveries as had been suggested before (Gurewitsch 2006).
A MEDLINE database search was conducted entering specific keywords and specific combinations regarding OBPI and c
section. These data were evaluated as well as the hospitals own data of the past decade.
As expected, the database search showed that BPI occurred very seldom after c section. The evaluation of the Cornell data
supported this. Publication of a paper is planned soon.
2.
Introduction:
Because of the recent cases of plagiarism in Germany, we were interested in the extent to which plagiarism occurs in medical
articles.
Methods and materials:
Editors of ObGyn journals and other medical journals were contacted in order to find out whether – and if so by which means –
submitted articles are checked for plagiarism.
Results:
Often articles are not checked before being published and many editors still rely on their reviewers. The results will be
published in a paper soon.
Note: Patricia Palten received funding for her BMEP time in the U.S. from the B. Braun AG/ Melsungen (Fellowship).
HANNES RANKE
Home Institution:
Host Institution:
University of Toronto Medical School, Toronto, ON, Canada
Research Mentor: Wolfgang Kübler, M.D., Ph.D., Associate Professor
of Surgery at University of Toronto Medical School, Toronto, ON,
Canada; Professor of Physiology at Charité, Berlin
Personal Reaction to the Canadian Experience:
Before I came to Canada I did not know much about this country. All I knew about Canadians was that they were extremely
friendly, great at ice hockey and famous for maple syrup. These things are all true, but there is much more to tell about
Canadians and their country.
First of all, Canadians do not like it when you tell them that they are like Americans. There are many similarities but you would
not say that Austrians and Germans are the same either. In general, the European influence is stronger than in the United States.
For example, there are much stricter gun laws in Canada.
Working in the lab at the hospital with people from all over the world is very rewarding. You can learn a lot from them because
each culture has its own unique elements. In Canada, specifically in a major metropolitan city such as Toronto, there are so
many different cultures that are proud to be Canadian but still retain the distinct elements of their own cultural background.
You can have amazing Indian or Chinese food almost anywhere in the city.
Canada is the second largest country in the world, and considering that it has only 34 million inhabitants, it has a very low
population density. Because of this, there are few companies that offer services like mobility coverage, and the lack of
competition results in monopolization and high prices for consumers.
So far, I have had a wonderful time in Toronto. I enjoy the culture and the friendliness of the people and I am looking forward
to what the next five months will hold. I am hoping to take some time to explore the country’s vast natural landscape.
After five months, my lab moved to a different building which created some challenges. Otherwise, there were no difficult
encounters at all. I got my work permit within one day: two hours after I walked through the door of the Canadian embassy in
Berlin. Canadian customs at the airport welcomed me very kindly and once I arrived at the hospital I got help from at least three
secretaries to deal with my paperwork, hospital ID and keys. Even on the streets of Toronto, as soon as I looked confused or
lost I got a friendly “may I help you?” from someone.
At the beginning of March I biked home from the hospital. It had not snowed for a while and no new snowfall was expected,
but somehow it snowed the entire day, even during my ride home. I had some difficulties riding my bike through 20cm of new
snow, but with the help of the snowplow and the tons of salt that it put on the street, and the careful Canadian drivers, my ride
home was much easier. I thought that all the drivers were smiling at me because nobody other than a crazy European would
bike in such weather, but I was wrong. Half-way home I was overtaken by 2 police officers riding their bikes who gave me a
friendly “good evening.” The situation became a little stranger when I overtook a policeman riding a horse two blocks later.
- Find your balance between working in the lab and enjoying your leisure
- Take the Megabus to New York or Montreal. The sooner you book a ticket the lower the price will be (free Internet is
available during the ride)
- The seasons are more extreme than in Germany, be prepared for a cold-icy winter and a hot muggy summer
- Do not forget to bring your ISIC student ID. It lowers the price of buses, museums, public transportation and other facilities.
- Live together with other roommates, this will improve your English quickly.
- Use blogto.com to discover Toronto.
Abstract on Research Topic – Hannes Ranke
Title: Role of Connexin 40 Protein, CFTR and TRPV4 channel in lung vascular adaptation of chronic hypoxia
Author: Hannes Ranke
Institutions: Department of Surgery, the Keenan Research Center at the Li Ka Shing Knowledge Institute of St. Michael’s,
University of Toronto, Toronto, Ontario, Canada
Department of Physiology, Charité - Universitätsmedizin Berlin, Germany
Introduction:
Hypoxic pulmonary vasoconstriction (HPV) terms a fundamental physiological response intrinsic to the pulmonary vasculature
which serves to optimize gas exchange by directing blood flow from poorly aerated to well ventilated areas of the lung. In
generalized hypoxia, intact HPV increases total pulmonary vascular resistance a thus contributes to the clinical pathology of
hypertension and cor pulmonale in chronic hypoxic lung disease.
Previous studies have shown the gap junction protein Connexin 40 or the chloride channels cystic fibrosis transmembrane
conductance regulator (CFTR) block the acute pulmonary vasoconstrictive response to hypoxia in general. HPV is also likewise
blocked in mice deficient in the polymodal cation channel transient receptor potential vanilloid 4 (TRPV4).
The signaling mechanisms underlying the acute and chronic effects of alveolar hypoxia on the pulmonary vasculature are still
unknown. It is unclear whether the acute hypoxic vascoconstrictor response, within seconds and the initiation of the structural
vascular remodeling process in chronic hypoxia are regulated by similar or different mechanisms. Connexin 40, CFTR and
TRPV4 are expected to play an important role in lung vascular remodeling, pulmonary hypertension and right ventricular
hypertrophy cause of chronic hypoxia.
The results of these experiments may explain new insights into the mechanisms regulation lung vascular adaptation to chronic
hypoxia. This knowledge could be use for novel targets for the treatment of pulmonary hypertension and car pulmonale in
chronic hypoxic lung disease.
A mouse model was applied. Connexin 40, CFTR and TRPV4 Knockout mice were compared to C57 wild type mice. Each
knockout breed and wild type mice were separated at the age of 8 weeks into 2 groups. The normoxia group was exposed for 35
days to ambient air. For the same amount of time the hypoxia group was exposed to 10% oxygen and balanced nitrogen.
After 5 weeks effect of different oxygen concentration hemodynamic measurements and histological analysis were performed.
The blood pressure of each mouse was measured over the left carotid artery catheter, the microtip Millar catheter was
introduced via the right jugular vein and advanced to the right ventricle for online recording of right ventricular endsystolic
pressure (RVESP). A tracheal tube was placed for supporting mechanical ventilation and further measurements with the
isolated lung set up.
The isolated lung set up created a full heart-lung circulation with Hanks’ balanced salt solution with 5% bovine serum albumin
and 5% dextran for ex vivo measurements of the pulmonary artery pressure under different flow rates. With the help of these
values the intrinsic pulmonary vascular resistance at a nominal vascular pressure of zero was calculated.
After completion of ex vivo hemodynamic recordings, weight of right and left ventricle was determinate for right and left
ventricular hypertrophy. Finally the lung tissue was used for histological analysis of lung vascular remodeling.
At the time of publishing this journal the hemodynamic and histological data of the TRPV knockout mice were not significant
enough. The experiments with the Connexin 40 and CFTR knockout mice groups had not started. This work will continue for
an additional five months.
Note: Hannes Ranke received funding for his BMEP time in Canada from DAAD.
TOM ROESCHEL
Home Institution:
Anatomisches Institut,
Charite Universitaetsmedizin , Berlin
Host Institution:
Department of Nephrology and Hypertension
Oregon Health and Science University
Portland, OR, USA
Research Mentor:
David H. Ellison, M.D., Professor of Medicine, Department Head at OHSU
and Staff Physician at the VAMC
I had spent some time in the U.S. prior to my BMEP exchange and I did not expect any surprises. I was wrong. All the time that
I had spent on the East coast had painted a picture that was completely different from what awaited me in Portland. No wonder
they call it “the city where young people go to retire”. Most people I met came to Portland because they found New York,
Boston and LA to be too stressful. They wanted to work less and live more, and that mentality seems to be very defining of the
Pacific Northwest. Work in the lab is different, obviously, but as soon as all papers are read, all animals fed, and every western
blot evaluated, there are hundreds of cafes, bookstores, and bars to be discovered.
The rain. Many Portlanders will tell you that it doesn’t bother them anymore, but they’re all lying. It rains every single day.
Occasionally there’ll be a couple of sunny moments vigorously used by everyone to walk the promenade by the Willamette
River, which winds through the city. I decided to go out for a run and sure enough I was greeted by heavy rain and hail as soon
as I was as far away from my apartment as possible. This was the day I decided to join a local gym.
Abstract on Research Topic – Tom Roeschel
Title: Slow pressor dose of ANG II in SPAK knockout mice
Author: Tom Roeschel
Institution: Division of Nephrology and Hypertension, Oregon Health and Science University, Portland OR, USA
Introduction:
The electroneutral cation cochannels, NKCC2 and NCC are expressed in the Thick Ascending Limb (TAL) and Distal
Convoluted Tubule (DCT), respectively. While they are responsible for the retention of 30% of the filtered sodium, they are of
major importance in the regulation of salt and water homeostasis by the kidney. Both channels are regulated, in part by the
Ste20p-related Proline Alanine-rich kinase (SPAK) pathway.
Angiotensin II (ANG II) is a peptidehormone, which, at a high pressor dose, promotes arteriolar constriction and at a slow
pressor dose inhibits Na retention by the kidney, both resulting in an increase in systolic blood pressure (BP). We hypothesize
that a slow pressor dose ANG II will increase systolic BP in WT mice while this effect will remain less pronounced in SPAK
knockout mice.
SPAK knockout and wildtype C57BL/6 mice (age 9 mo.) were infused with ANG II (400 ng/kg/h) for 21 days with
subcutaneous osmotic minipumps. Systolic BP measurements were assessed with the tail-cuff method. Mice were acclimatized
to the BP machine 10 days prior to the infusion of ANG II.
On day 21, mice were transferred into metabolic cages and 24-h urine samples were collected. Urine Na content was detected
with flame photometry and normalized to urine creatinine concentration, assessed with a commercially available ELISA-kit.
Na/creatinine ratios did not differ significantly between SPAK knockout and wildtype animals, ensuring normal kidney
function in both groups.
Baseline systolic BPs did not differ between the two groups. During the first week of ANG II infusion, systolic BP were an
average of 31 mmHg higher in the wildtype group then in the SPAK knockout animals, and decreased to an average of 10
mmHg difference by the end of the 21-day study period. Differences in systolic BPs were statistically significant from day 6 to
day 21. Systolic BPs did not differ significantly from baseline to day 21 of ANG II infusion, suggesting chronic regulatory
mechanisms opposing the effects of slow pressor dose ANG II. Results obtained in this study suggest the involvement of SPAK
in ANG II mediated effects on systolic blood pressure in mice.
Note: Tom Roeschel received funding for his BMEP time in the U.S. from DAAD.
NORMAN RUSSKAMP
Home Institution: FAU Erlangen-Nürnberg
Host Institution:
The University of Michigan, Ann Arbor, MI, USA
Research Mentors:
Prof. Peter A. Ward, M.D.
Dr. med. Markus Bosmann
The most important experience I personally had during my time in the United
States was to realize that it does not matter where in the world you are, but with
whom you are. Ann Arbor is such a diverse place and you just happen to meet the
most interesting/fun/open-minded/intelligent/creative people from all over the
USA and beyond on the streets, at the bar or some other random location. The Ann Arbor spirit is really special.
Looking back, luckily all obstacles were manageable quite easily. But of course I had heard from friends who encountered real
difficulties in the visa application process (or better: roulette), and thus was more than relieved to set foot on American ground
for the first time.
Another far simpler problem was to find a place to live in the beginning of fall semester in Ann Arbor. It turns out that people
apply for apartments as early as 8 months in advance and I really had some trouble to find a suitable place.
Ann Arbor, a Saturday around midnight in mid-January, temperatures around -10°C…
D.M.: “Hmm, I’m bored…let’s build a gigantic sphinx out of snow!”
His roommate’s Facebook status the following day:
“Coming home after a weekend at my parents’ place only to find a giant snow sphinx in our front yard overlooking all of White
St.”
 American animals are both smellier and more vicious than European animals. Their ferocity is partially due to their
general obesity. Do not feed any wild animals you see, no matter how cute they seem, with one single exception:
feeding squirrels under professional supervision by members of The University of Michigan Squirrel Club is both safe
and strongly recommended.
 Plus, make sure to avoid only making friends who speak your native language.
Abstract on Research Topic – Norman Russkamp
Title: Implications of the cytokines IL-17A and IL-27p28 in Acute Lung Injury
Author: Norman Russkamp
Institution: Department of Pathology, Laboratory of Peter A. Ward,
The University of Michigan, Ann Arbor, Michigan, USA
Introduction:
Acute Lung Injury (ALI) is a major cause of hospitalization and death in the industrialized world and is most often encountered
in conjunction with systemic inflammatory syndromes like sepsis and SIRS. The key features of this disease are dyspnea, influx
of neutrophils into the alveolar compartment and the development of a pulmonary protein-rich edema fluid resulting in a
reduced PaO2/FiO2 ratio. In the pathophysiology of ALI, the abundant production and release of a multitude of proinflammatory cytokines plays the most prominent role. As an acute inflammatory disorder, innate immune cells are first in line
to respond to the disease causing stimuli and are thus responsible for the rapid onset of the large number of deleterious
symptoms. Accordingly, the focus of our lab’s research on ALI lies in investigating the cellular source(s) and contribution of
the cytokines IL-17A and IL-27p28, whose importance in mucosal host defense is as well known as their role in various autoimmune diseases.
The rodent models of mouse endotoxin-induced lung injury and immune complex induced lung injury serve to mimic the
pattern of human ALI in our lab. The comparison of differences between the two etiologically distinct models especially
provides us with valuable insights into the pathomechanisms underlying the acute phase of the disease in the timeframe from 2
to 12 hours. Most analyses are performed in the pulmonary fluid collected from broncho-alveolar lavage and in the harvested
organs themselves.
In order to determine the whole spectrum of pathologic alterations, we are investigating the collected material by assessing
changes at cellular and molecular levels: cell populations are described and sorted by fluorescence-activated cell sorting
(FACS), protein concentrations are measured by enzyme-linked immunosorbent assay (ELISA) and Bioplex. Gene expression
in the affected tissue is determined by RT-PCR and, furthermore, the activation state of intracellular signaling molecules is
studied with newly developed technologies like Phosflow and Phosphoprotein Bioplex analysis. Complemented by the use of
different knockout animal strains, this variety of methods allows us to draw a consistent image of the in-vivo aspects of ALI.
Results:
Consistent with elevated gene expression, high levels of both IL-17A and IL-27p28 are being released into the alveolar
compartment during ALI. Depletion of alveolar macrophages results in reduced concentrations of the cytokines, indicating this
cell type’s contribution to the pathomechanism of the disease. However, data from several experiments suggest that a multitargeted approach will be essential to moderating mortality in human ALI. IL-17A and IL-27p28 contribute to pathologic
alterations and the evaluation of their role in the disease will thus be valuable for understanding the causes of the disease, as
well as for estimating the impact of future pharmacological interventions.
Note: Norman Russkamp is funded through an M.D. fellowship by the Boehringer-Ingelheim Fonds for basic medical research.
BASTIAN O.T. SABEL
Home Institution:
Ludwig-Maximilian University Munich, Faculty of Medicine
Host Institutions:
DKFZ – German Cancer Research Center, Heidelberg, Germany
and
Department of Radiology, Massachusetts General Hospital, Harvard Medical School,
Boston, MA
Research Mentors:
Soenke Bartling, MD
 Radiologist and Post-Doc at the DKFZ Heidelberg
Rajiv Gupta, MD, PHD
 Assistant Radiologist, MGH
 Director, Ultra-high Resolution Volume CT, MGH
 Instructor, Harvard Medical School
For my entire life, I planned to spend a longer time in the United States. I had traveled to the US several times - for
conferences, clerkships and holidays - and I always loved it. I heard about the BMEP program from a former participant. I later
applied and got accepted. I finally arrived at the Massachusetts General Hospital in Boston in February 2011. It was and still is
overwhelming. The omnipresent brainpower, the academic network, working together with some of the world’s most famous
research facilities and scientists form an academic atmosphere with a very stimulating flair and spirit. All the people were very
kind and I was integrated in the team from the beginning. Since the technical equipment has a high impact especially in the
field of Radiology, it was absolutely fascinating to work with the most modern technology and prototypes for clinical imaging
in the largest radiology department of the world.
Teaching plays a great role at the MGH and is among the best I’ve ever experienced. That is why I was also very happy to get
the opportunity to take part in clinical rotations and the daily resident’s seminars.
Boston is a terrific place to live. The city is international and intellectual in a way that I have never experienced before. If you
come to Boston and face people with an open mind, you will get an extraordinary opportunity to experience a great variety of
different life styles. On one day you visit a fascinating Asian karaoke-party in Chinatown and on the next day you are invited to
celebrate Passover with Jewish friends. In conclusion I can say that many of the most interesting people I have met in my life, I
met in Boston.
Greatest Difficulty Encountered:
The most difficult and most time-consuming process was certainly getting the DS 2019 form from the host university.
Among many funny situations in Boston I also had the best cab ride ever. Two fellow BMEP students and I were on our way in
a cab when one of them decided to pretend he was French in front of the cab driver. His accent was exaggerated but convincing
and not to forget: hilarious.
Future BMEP students also going to MGH should clearly point out that they are still undergraduates. Then Harvard University
issues the DS 2019 instead of PartnersHealth, and this truly accelerates the procedure.
Abstract on Research Topic Since my Academic Year took place in two different institutions, and I was just getting started on my projects in Boston when
the deadline for this yearbook arrived, there were no results gained at the Department of Radiology, Massachusetts General
Hospital, Boston, that could be presented on these pages. Attached is a report on the project that I worked on and completed
during my time at the DKFZ – German Cancer Research Center, Heidelberg, Germany.
Title: Introduction of macrophage-ablation animal models into bio-medical imaging research
Institution: DKFZ – German Cancer Research Center
Authors: Sabel 1,2, Bäuerle1, Brand3, Semmler1, Bartling1
1 Dept. of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany
2 Dept. of Radiology, Massachusetts General Hospital, Boston, USA
3 Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
Introduction:
Macrophages as an integral component of the reticulo-endothelial system engulf foreign particles such as larger imaging
probes. This is pivotal for bio-medical imaging in two ways. First their phagocytic ability is utilized to enhance macrophagerich tissue such as the reticulo-endothelial system. Liver tumors and metastases lose their phagocytic capacity, and therefore do
not enrich imaging probes allowing them to be distinguished from healthy tissue. Secondly, unspecific phagocytosis reduces the
circulation time of imaging probes, especially if the imaging probes are above a certain size range. This is a significant
limitation in molecular imaging because a short circulation time reduces the chance to reach sufficient local enhancement in the
case of targeted imaging concepts. Macrophage ablation animal models have existed for a long time (1,2), and they may be a
valuable research tool to investigate, manipulate or prevent unspecific probe uptake. The aim of this study was to introduce this
tool into biomedical imaging by showing its power to manipulate significantly the kinetics of larger imaging probes.
Methods:
The kinetics of a commercially available CT contrast media was compared in macrophage ablative mice and normal mice.
An established macrophage ablation model was used (1,2). Therefore, 220 µg liposomes, loaded with clodronate at a
concentration of approximately 7 mg/ml, were injected into the peritoneum of each of 3 female C57BL/6 mice. On the third day
after the clodronate application, 200 µl of the particulate agent ExiTron nano 6000 were injected into three macrophageablative mice, as well as three control mice. CT scans were acquired before and 3 minutes, 1, 6, 24 hours after the ExiTron
application. Subsequent to the last scan, the animals were sacrificed; spleens and livers were removed. Relative CT values
(CTV) were measured and analyzed.
Results:
Liver and spleen enhancement of treated as well as of controls was increasing over time. However, the mean peak values were
different with 218 CTV (min 184/max 252) for ablative and 622 CTV (min 480/max 805) for control mice in the liver and 443
CTV (min 350/max 508) for ablative and 1017 CTV (min 523/max 1553) in control mice in the spleen. Kidney enhancement
showed little difference with 74 CTV in ablative and 71 CTV in control mice in peak enhancement at one hour. Muscle showed
no enhancement.
Conclusion:
Macrophage-ablation leads to a significant decrease in enhancement in organs containing high numbers of macrophages, such
as liver and spleen, but only marginal changes in macrophage-poor organs, such as kidneys. Therefore, we conclude that
macrophage ablation can significantly influence the (unspecific) phagocytotic activity and thus open new potentials to
investigate and manipulate uptake of imaging probes.
References:
1.) The effect of elimination of macrophages on the tissue distribution of liposomes containing [3H]methotrexate. Claassen
E, Van Rooijen N., Biochim Biophys Acta. 1984 Dec 20
2.) Transient suppression of macrophage functions by liposome-encapsulated drugs. van Rooijen N, Bakker J, Sanders A.
Trends Biotechnol. 1997 May;15(5):178-85
Note: Bastian Sabel received funding for his BMEP time in the U.S. from DAAD.
LAURA KATHARINA SCHENK
E-Mail: [email protected]; [email protected]
Home Institution:
Westfälische Wilhelms-Universität Münster
Experimentelle Nephrologie, Med. Klinik D
Host Institution:
Epithelial Systems Biology Laboratory
National Heart, Lung and Blood Insitute,
National Institutes of Health, Bethesda, MD
Research Mentors:
Mark Knepper, M.D., Ph.D., chief
Trairak Pisitkun, M.D., Ph.D., staff scientist
Spending a year researching in the U.S. is an amazing experience! Having studied in several European countries during my
time in Medical School, my year at the National Institutes of Health in Washington D.C. was still a unique experience.
Washington is a nice place with great museums and National Parks for hiking nearby, but surprisingly small-townish in several
aspects. However, in order to have yourself overwhelmed by contemporary art, music and nightlife you can easily get on the
bus to New York City.
I particularly enjoyed the fruitful, stimulating research environment and having supportive, instructive and friendly mentors. I
also enjoyed having to take personal responsibility for my work. This strongly supported my propensity towards research and
helped me to define a career on the bridge between clinical work and basic research as my goal.
During my time in D.C., I met great people: welcoming, helpful and a lot of fun! Sharing holidays such as Thanksgiving or
President‘s Day with American friends was amazing, as well as spending Christmas Day helping with an underprivileged
peoples’ meal at the local church.
However, I was sometimes astonished by the Americans’ stoicism. Neither the fact of having electrical power cut in urban
winter Washington D.C., lasting an entire week without the culprit branch on the power line being removed, nor the threat of a
potentially month-long furlough for government employees during the negotiations over the budget could lead to a noticeable
uproar among the intelligent inhabitants of this liberal, democratic country.
1. Getting your visa requires a lot of personal effort, but also patience and faith.
2. Take advantage of your stay. Explore, investigate, travel, learn, enjoy! You can sleep later when back in Germany ;-)
Remember to take your I.D. when going out (even for dinner, unless you look like a pensioner). Remember activating your
debit card for use in the U.S. T-Mobile U.S. has reasonable prepaid cell phone offers.
Abstract on Research Topic – Laura Katharina Schenk
Title: Global proteomic profiling of vasopressin-dependent nuclear protein shuttling
Author: Laura Katharina Schenk
Institution: Epithelial Systems Biology Laboratory; National Heart, Lung and Blood Institute; National Institutes of Health;
Bethesda, MD
Introduction:
Released in response to increases in plasma osmolality and decreases in blood pressure, AVP leads to an acute increase in renal
water reabsorption mediated by the insertion of aquaporin-2 (AQP2) water channels into the apical membrane of collecting
duct principal cells. Downstream effects of AVPR2 activation include a range of transcriptional changes. A variety of proteins
can be involved in the regulation of gene transcription in kidney inner medullary cells upon stimulation with AVP, e.g. via
alteration in their nuclear abundance. Regulated nucleo-cytoplasmatic shuttling has been described for several classes of
proteins which can be involved in the regulation of gene expression, such as transcription factors, cofactors and molecules
involved in post- translational modification. The goal of my project was to use protein mass spectrometry to identify proteins
that move into and out of the nucleus if collecting duct cells in response to vasopressin.
Global proteomic profiling via LC-MS/MS was carried out on the proteomically well characterized mpkCCD (clone 11)
collecting duct cell line. Cells were grown metabolically labeled using Stable Isotope Labeling of Amino acids in Cell culture
(SILAC) before being subjected to 60 min. of treatment with vasopressin. A commercial kit (NE-PER®; Pierce) was utilized to
separate soluble nuclear extract and nuclear pellet from the cytoplasm. Peptides were identified and quantified by protein mass
spectrometry, followed by bioinformatic evaluation. Changes in protein abundance were verified by immunohistochemnistry,
Western Blotting or targeted ion selection on the mass spectrometer.
We identified >400,000 peptides corresponding to 4000 unique proteins in our nuclear fractions. A large number of the proteins
we identified which changed in abundance by vasopressin contribute to the regulation of transcription. E.g. Elf1, Elf3, jun-B,
AP1, CREB-binding protein and Forkhead Box Proteins have putative binding sites in the conserved 5‘-flanking region of the
AQP2 promoter and other collecting duct specific genes. However, cell adhesion molecule nuclear signaling by vasopressin via
several isoforms of catenins and actin binding proteins, could be shown. For several proteins a novel role in vasopressin
signaling could be established.
Note: Laura Katharina Schenk received funding for her BMEP time in the U.S. from the DAAD.
KIRILL V. SOLOVYOV, PH.D.
Home Institution:
Department of Molecular Genetics
Institute of Experimental Medicine
North-West Branch of Russian
Academy of Medical Sciences
197376, Akad. Pavlov Str., 12
Saint-Petersburg, Russia
Home Research Mentor:
Vadim B. Vasilyev, M.D., Professor of Medicine
Host Institution:
Lab of Molecular Biology of Peptide Hormones
Max-Delbrueck-Center for Molecular Medicine (MDC)
Berlin-Buch, Robert-Rossle-Str. 10
13125 Berlin, Germany
Host Research Mentors:
Michael Bader, Professor, M.D., Nataliya Alenina, Ph.D.
Personal Reactions to the German Experience:
Everything is highly organized in Germany (in the city and also in the laboratory), especially the separation of garbage. For me
it was a surprise that baskets for different types of waste had different colors: paper – blue, glass – green, other waste – yellow.
I find that the technology of waste-recycling is very nice and important. I hope that in the near future this technology will be as
widespread in Russia as it is in Germany.
During my staying in Berlin there were no problems or difficulties at all.
During the whole period of my work in the lab I was included in the list of “round emails”, where all members of the lab
discuss all current news and problems. I returned home a long time ago, but I continue to receive all these emails, so I'm still
involved in the German lab life. Most of these messages are very funny:
- Dear All, I would like to know whether anybody might have taken 24-well plate from the fridge. I put it into the fridge and it
was gone. As far as I know, cells were fixed with PFA so I guess I can exclude any cell migration out of the fridge like snails
with their homes on their back!
- Dear All, my car is broken and the buses are not running this morning because of the snow, so I need to work from home
today.
- Dear All, I had the surprise to find my labcoat in the wastebasket of the office. I admit I was wrong to keep this labcoat in the
office and I won't do it again (although I was only doing so to avoid other people using it, as sometimes happens).
- Who forgot big agarose gel is running?????..... I switched it off around 4pm.
It is recommended that you always wear a white coat and gloves in the lab.
Abstract on Research Topic – Kirill V. Solovyov, Ph.D,
Title: Obtaining of the DNA Construct for Studying the Regulation Effect of B2VNTR in Eucariotic Cell Cultures
Author: K.V. Solovyov
Institution: Max-Delbrueck-Center for Molecular Medicine (MDC), Berlin-Buch
Introduction:
The major goal of this project is development of novel approaches to searching for new risk factors and early presymptomatic
diagnosis of cardiovascular disease, including hypertension and ischemic heart disease. Main attention is paid to the specific
role of nonprotein coding of bradykinin receptor gene B2VNTR and its possible epigenetic modification. We decided to create a
model system for studying the expression and regulation of a reporter gene (EGFP) by B2VNTR sequence in vitro in eucariotic
cell culture. Perhaps it will be possible to find B2VNTR regulating effect by changes in intracellular EGFP fluorescence. We
used T-Rex system (Invitrogen) as a template for creation DNA construct contained EGFP gene followed by B2VNTR.
For PCR amplification of the human B2VNTR we used previously created construction pGEM-T-Easy vactor (Invitrogen)
containing B2VNTR sequence as a template. The forward primer 5'GTCTAGAATAACTTCGTATAGCATACATTATACGAAGTTATCTCAGCAACCAAGGGATTGT - 3' contained 5'-clamp (g),
XbaI cloning site (TCTAGA) (underlined), LoxP sequence and the beginning of B2VNTR sequence. The reverse primer 5'GACCGGTATAACTTCGTATAATGTATGCTATACGAAGTTATGGTCAGGATTTATGGGCTCTT - 3' contained 5'-clamp
(g), AgeI cloning site (ACCGGT) (underlined), LoxP sequence and sequence encoding terminus of B2VNTR. The thermal cycle
was as follows: 95oC for 5 min, 30 cycles at 95oC for 1 min, 60oC for 1 min, and 72oC for 1 min, followed by an end elongation
step of 72oC for 10 min. The PCR-product was purified using WizardSV Gel and PCR Clean-Up System (Promega). We cloned
B2VNTR into XbaI-AgeI cloning sites of the expression vector pcDNA4/TO/Myc-His-A from “T-REx™ Complete Kit with
pcDNA™4/TO/myc-His©” (Invitrogen) containing EGFP cDNA. Vector pcDNA4/TO/Myc-His-A-EGFP-B2VNTR carried
ATG (start-codon) followed by EGFP сDNA sequence, and B2VNTR sequence. One microliter of the ligation reaction was
transformed into DH5α competent cells by electroporation. Assaying of positive clones was performed by miniprep followed
by sequencing.
Results:
As a result we have got a plasmid coding EGFP followed by B2VNTR, which allows us to study the regulating effect of
B2VNTR sequence to EGFP expression in eucariotic cells. A corresponding plasmid also contained the LoxP sites for excluding
B2VNTR sequence from the plasmid with help of Cre recombinase. This can help to obtain the “control” plasmid containing
only EGFP gene (without B2VNTR sequence) for estimation of the basal level of the expression of this protein in transfected
cells.
Conclusions:
The results of the project may help in future to provide new insights into molecular mechanisms, modeling and diagnosis of
cardiovascular diseases, understanding of the mechanisms of interaction between this gene and other factors and toxicogenic
effects.
Note: This work was supported by IALS - B.Braun Fellowship.
Nataliya Alenina, Ph.D., Kiril V. Solovyov, Ph.D., and Michael Bader, Professor, M.D.
Kiril Solovyov, Professor Michael Bader, and the scientific team in the cell-culture room
BIANYING SONG
Home Institution:
Peter L. Reichertz Institute for Medical Informatics,
University of Braunschweig – Institute of Technology
and Hanover Medical School
Host Institution:
Department of Biomedical Informatics,
Vanderbilt University, Nashville, Tennessee
Research Mentor:
William Gregg, MD, MS, MPH
Assistant Professor of Biomedical Informatics and Medicine
It is my great honor to participate in the BMEP and the B.Braun/IALS Fellowship Program. Many thanks to my advisors Prof.
Marschollek, Prof. Haux at the home university and Prof. Gregg at the host university, as well as Prof. Stolte, the President of
International Academy of Life Sciences.
With more than 65 faculty members, the Department of Biomedical Informatics (DBMI) at Vanderbilt University is the largest
academic DBMI in the US. Working there enabled me to learn a lot and to meet many nice friends.
At the beginning of my stay in the US, I thought I was able to withdraw US dollars from my German account in Nashville, but
actually I couldn’t! So I had to open an account at the Bank of America and ask my friends to transfer money to me. It was a
great difficulty I encountered.
When I traveled back from St. Louis to Nashville, I took the bus and then a funny thing happened. The bus driver did not know
the route! The driver asked people at some gas stations the right way. Thank goodness, we finally found the right way back to
Nashville safely.
- To prepare to answer questions at the time of entry into the US.
- To use local mailing-lists and web sites to get useful information.
- To have a car in Nashville.
- To know people with different backgrounds in the US.
Abstract on Research Topic – Bianying Song
Title: Prediction of patient admission and emergency department visit based on clinical and administrative data within an
electronic medical record
Authors & Institutions: Bianying Song1, 2, William Gregg2, Josh Peterson2, Reinhold Haux1 and Michael Marschollek3
1
Peter L. Reichertz Institute for Medical Informatics, University of Braunschweig – Institute of Technology and Hanover
Medical School, Braunschweig, Germany
2
Department of Biomedical Informatics, Vanderbilt University, School of Medicine, Nashville, Tennessee , USA
3
Peter L. Reichertz Institute for Medical Informatics, University of Braunschweig – Institute of Technology and Hanover
Medical School, Hannover, Germany
Introduction:
Hospital admissions and emergency department (ED) visits generate large costs for health care. Predicting patients’ risk of
admission or ED visit could improve resource planning. The objective of our research is to construct and evaluate models
which predict patient admission and ED visit based on clinical and administrative data recorded within the electronic medical
record within the previous year.
The de-identified data used in this study was drawn from StarPanel within Vanderbilt University Medical Center’s adult
primary care clinic. Patients with visits in the years 2008, 2009 and 2010 were included, yielding 22969 longitudinal records.
Eight variables were extracted: sex, age, #hypertension medications, #diabetes medications, admission, ED visit, appointment
and primary care visit.
Patient admissions and ED visits were combined into a single variable (AD&EV) using a plus function. Patients were firstly
classified using a K-mean algorithm based on the different single parameters e.g.: AD&EV, appointment… Decision tree,
linear regression and logistic regression were used to predict the patient AD&EV based on multiple patient parameters in the
previous year. The performances of these models were evaluated by receiver operating characteristic (ROC) curves. The
models were constructed based on the data in 2008, 2009 and evaluated based on the data in 2009, 2010.
Linear regression, logistic regression and decision tree models for the prediction of patient admission and ED visit based on
clinical and administrative data have been constructed. The area under the ROC curve (AUC) for the linear regression, logistic
regression and decision tree models are: 0.688, 0.686 and 0.628, respectively. The AUC values of all of the models are lower
than 0.7. To achieve a better performance, the inclusion of more clinical parameters in future models appears necessary.
Note: Bianying Song received funding for his BMEP time in the U.S. from the B. Braun Foundation, Melsungen.
TIM ULLRICH
Home Institution:
Klinikum Georg-August-Universität Göttingen
Host Institution:
Vanderbilt University Medical Center, Nashville, Tennessee
Research Mentor:
Joern-Hendrik Weitkamp, M.D., Assistant Professor of Pediatrics
Going abroad for a certain period, most people have a few things in mind they expect, which
are probably learning the language, profiting from the professional facilities and excellent
teachers, getting to know a different lifestyle and point of view, and, last but not least, having
a fascinating, exciting time with a whole bunch of new experiences they would never forget. I
am in the lucky position to be able to say that all my expectations have been fulfilled. The
Nashville Medical Center combines a brilliant research institution, a huge hospital with every conceivable field of
specialization and a great network of excellent professors. The Vanderbilt Campus is a wonderful place, where I spent most of
my time. It contains not only the work places but also a huge park and several nice spots to enjoy the hot summer sun as well as
the incredible sport facilities for students and the great college parties at night. Nashville itself also offers lots of distractions.
Known as Music City, Nashville all is about music. The big and famous country scene is reflected in numerous music bars and
restaurants; also for other kinds of music. Nashville’s professional hockey and football teams are a must for every visitor.
Around Nashville there are a lot of very attractive spots for outdoor activities, such as whitewater rafting, canoeing and hiking.
Altogether the BMEP offers a great experience and I am very happy that I could benefit from it.
I had a few difficulties finding the right place to live. Since my arrival did not fall on the same date as the semester start for the
American students, there was not much fluctuation regarding housing opportunities, especially close to the campus. Apart from
that - the visa of course!
There are too many to count. Anyway, one very special evening a friend and I realized that the whole university was going to
an annual on-campus outdoor music festival. Having no tickets, we were already on the way home. But then, as fate willed, we
found 2 brand-new tickets on the floor and had the most fun possible at the festival.
I would really recommend organizing housing as early as possible (craigslist). As soon as you have something you can start
concentrating on all the important things. You can still change your apartment after you have made some friends. Plus, all the
catastrophes occurring before and during your BMEP year are part of the experience ;)
Title: Anti-inflammatory features of vitamin A and its metabolites in NEC - Tim Ullrich
Authors: Tim Ullrich, Joern-Hendrik Weitkamp MD
Institution: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Introduction:
Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants and the exact
pathogenesis is unknown. Intestinal epithelial barrier disruption, followed by bacterial translocation and fulminant
inflammation resulting in necrosis are a hallmark of the disease. Immaturity of gastrointestinal immune regulation may
predispose preterm infants to NEC. Lamina propria FOXP3+ T regulatory cells (Treg) and intraepithelial lymphocytes bearing
the T-cell receptor  ( IEL) are critical for immune homeostasis and intestinal integrity. These cells are diminished in
number and proportion in NEC patients. Vitamin A (all-trans retinol) has been found to accelerate wound healing in injured
full-thickness porcine ileum explants. Moreover retinoic acid, a downstream metabolite of vitamin A has been revealed to
induce generation of Tregs and at the same time to inhibit generation of inflammatory Th17 cells in peripheral blood circulation.
Immunohistochemistry has been performed on human tissue samples from surgery explants using antibodies against (retinol)
alcohol dehydrogenase1 and (retinal) aldehyde dehydrogenase (key enzymes in vitamine A metabolism) in order to detect
location and volume of vitamin A metabolism in different parts of the gastrointestinal tract. We analyzed surgically resected
bowel specimens from 12 NEC patients and 16 controls (atresia repair, spontaneous intestinal perforation or ileostomy
takedown).
Vitamin A metabolizing enzymes have been found throughout the whole gut suggesting a major role for vitamin A metabolites
in intestinal immune homeostasis presuming the previous findings. Metabolizing systems have been found in NEC patients and
unaffected controls. Further experiments using multi-color flow cytometry will be done to reveal if the amount of vitamin A
metabolism is altered in affected samples.
Note: Tim Ullrich received funding for his BMEP time in the U.S. from DAAD.
ALEXANDER VOGT
Home Institution: Universität Rostock
Host Institution: Rockefeller University, New York, NY, USA
Research Mentors: Charles Rice, Ph.D., Head of Laboratory, and Marcus Dorner,
Ph.D., Post Doctoral Fellow
I have just arrived in New York. It is such a vibrant and fascinating city. The campus of
my University, which is also the place where I live, is located on the Upper Eastside of
Manhattan Island. That is fantastic for eating, going out, or simply enjoying New York.
The diversity is what makes New York so intriguing, especially when it comes to eating,
since you can taste food from all parts of the planet. My perfect day (off) in New York
starts with a jog in Central Park and a real bagel (cooked and baked) for breakfast. Then I go to one of the great art museums
(Museum of Modern Art, Metropolitan, Guggenheim), followed by fantastic Chinese food in Chinatown. In the afternoon,
SoHo and the Meatpacking district invite you to walk by. After a snack in a nice French café, a concert in the Carnegie Hall is
just the right thing to end the day. On the way back home you just want to sing Frank Sinatra’s: “New York, New York … da
da da da…”
In the two months that I have been here I have also made trips to Washington and Boston. Both are lovely cities and I can
highly recommend going there. A lot of my expectations of the United States and New York have been proven true, both good
and bad ones.
So far everything has gone fine. Obviously getting the visa might cause some minor problems, but as soon as one has all the
documents from the university, the rest is just bureaucracy. Before I came here there was some confusion about the housing,
but finally the University offered me a very decent spot on campus.
I really enjoyed the trip to Boston for the Forum II, not only because the presentations were interesting and UMass was a great
and generous host for us, but because it felt like being on a class trip again. Great fun!
First sort out everything well in advance! To avoid stress I would apply for the visa and housing early. In the end there is
always a solution, but you can avoid trouble and stressed phone calls by planning a bit ahead. Once you are there, just enjoy
everything and try to make the most out of your work and leisure time.
Abstract on Research Topic – Alexander Vogt
Title: A mouse model for Hepatitis C
Author: Alexander Vogt
Institution:
Department of Virology, Rice Lab, Rockefeller University, New York City, USA
Introduction:
With over 150 million infections, Hepatitis C is a serious worldwide health concern and new drugs and vaccines are required to
tackle this global challenge. Research on Hepatitis C has been hampered by a lack of a suitable small animal models, since the
Hepatitis C Virus only infects humans and chimpanzees. Chimpanzee experiments are not only very cost-intensive, but also
morally questionable. Our research group is trying to overcome the species-specific hindrances in mice to use them for the
study of Hepatitis C, especially for the testing of drugs or the development of vaccines.
For the ongoing work we are using animals in which human genes for HCV entry factors have been introduced. HC viruses
with fluorescent reporters, like Gaussia or Firefly luciferase, are injected into the mice and the viral infection is monitored.
By combining several different mouse strains and introducing adenoviraly delivered genes, we hope to obtain mice which
support the whole lifecycle of HCV.
The work is still ongoing, so no conclusions have been reached. However, the first results look promising.
Note: Alexander Vogt received funding for his BMEP time in the U.S. from DAAD.
YIN YU
Home Institution:
Rheinisch-Westfälische Technische Hochschule Aachen, Germany
Host Institution:
Endocrine Unit Research
Massachusetts General Hospital, Harvard Medical School, Boston, MA
Research Mentor:
Harald Jüppner, MD
Boston, “Hub of the Universe” and one of the oldest cities in the United States, shows
you the perfect mix between European flair and the American way of life.
Of course at the beginning I was totally overwhelmed and lost in this big country and especially in the supermarkets.
Everything you want to buy is either XXL and unhealthy, or healthy and therefore really expensive. The first days you see all
your prejudices coming true, meeting Americans who always ask you “Hello, how are you?”, and then pass by without waiting
for an answer, but after a few days you learn that this place is nothing that you could ever possibly have expected. Seeing 99%
of the people reading a book on the T(subway), meeting interesting people to whom you can talk about “God and the world”,
walking around and finding yourself at the top of the Bunker Hill Monument.
What I really love about this place are the people – every new person has something interesting to share, even just waiting at a
bus stop.
This experience has definitely opened my eyes, even though I have only been here for 1.5 months. My sojourn has already been
challenging and joyful in equal measure and I am confident that the remainder of my stay in the United States will be even
more enriching.
To end my first impression of Boston, I just want to repeat a general Bostonian truism: “If you don't like the weather, just wait
5 minutes.” Always check the weather before you go out of the house, you never know what to expect!
You will face a lot of problems, sometimes even before you can touch American ground, such as negotiating the visa
application process. There are so many things to say, but I will only point out the climax of this nightmare for me, and that was
standing in line for 4 hours outside the consulate in Frankfurt in temperatures of -10° Celsius.
The second problem that I had to face was being a “Student Intern” in Harvard because having this status does not bring you
any advantages. You can't get a T-pass for $20, you have to pay $59 instead; you can't go into the library or any other building
of the University requiring official admission; you don't get any discounts, etc. But even without these advantages, life in and
around Harvard Yard makes it all worthwhile and you will find ways to solve problems without the Harvard ID.
Never let your friends fool you when they say you HAVE to try American “delicacies”: you will end up eating things like
Maccaroni and Cheese, Peanut Butter and Jelly, and so on.
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Things to do: Freedom Trail, MIT Museum, Boston Symphony, free Campus Tours
Places to eat/drink: Burdicks (Hot Chocolate), Quincy Market (Clam Chowder), The Druid, The Black Rose (Beer)
Living: Craigslist
Facilities: Cambridge Library card, T-Pass
Abstract on Research Topic – Yin Yu
Having only been in the US for a short period by the time the Yearbook deadline arrived, I can merely provide a short
description on the projects on which I am working.
Institution: Department of Endocrinology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
Projects: I am concurrently working on three projects which respectively deal with:
a) Hypoparathyroidism
b) Pseudohypoparathyroidism
c) Nephronophthisis.
In all 3 projects, known disease-causing mutations have been excluded, allowing us to isolate what appear to be novel forms.
While in the families of research interest, the trend for hypoparathyroidism appears to be autosomal dominant, both
pseudohypoparathyroidism and nephronophthisis are,by contrast, autosomal recessive.
At this stage of our research, we are in the process of recruiting both affected and unaffected family members for a linkage
search in relation to our studies on hypoparathyroidism. We have already conducted linkage searches for
pseudohypoparathyroidism and nephronophthisis in order to search for mutations, with the linkage peak seen at Chromosome 7
for the former and Chromosome 3 for the latter. It is still uncertain whether mutations exist for pseudohypoparathyroidism;
however, we have unambiguously shown that there are no mutations associated with nephronophthisis in the coding regions.
Note: Yin Yu received funding for her BMEP time in the U.S. from the German National Merit Foundation.
Prof. Winston Langley, Ph.D., Provost Univ. of Massachusetts; Joe Byrne, Ph.D., Provost em. Tufts University;
Prof. Siegfried Geyer, Ph.D., Medizinische Hochschule Hannover
Academic year 2010/11
Boston Forum II
Friends of BMEP and IALS – Financial Support since 1985
The International Academy of Life Sciences (IALS) and its subsidiary, the Biomedical Sciences Exchange Program (BMEP),
wish to express sincere gratitude to the individuals and organizations listed below who have contributed to the FRIENDS OF
IALS since the 1985 appeal for financial support.
Benefactors – up to 5000 Euros
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Dr. Michaela Banck and Dr. Andreas Beutler, Mayo Clinic, Rochester, MN
Prof. Claudia Barth, Köln
Dr. Dennis Dey, MIR Neurology & Spine Center, Cumberland, MD
Brita Dole, Bad Oeynhausen
Prof. Karsten Dreinhöfer, Berlin
Dr. Heinrich Hagehülsmann & Ute Hagehülsmann, M.A., M.Sc., Rastede
Sabine Hermann, DMD, Löhne
Prof. Roland Hetzer, Berlin
Dr. Holger Kranich, Gila River Health Care Corporation, Phoenix,AZ
Fr. Vöth Naber & PD Klaus Naber, Murnau
Drs. Marion Schaeffer & Jürgen Schaeffer, Hannover
Patrons – up to 1000 Euros
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Dr. Dr. Elmar Burchhardt, Cambridge, Massachusetts
Dr. William Deal, Dean em., Birmingham, Birmingham, AL
Prof. Torsten Doenst, Freiburg
Prof. Harald Jüppner, Harvard Medical School, Boston, MA
Dr. Frank-Dieter Loitz, Braunschweig
Dr. Christian Schäffer, Stuttgart
Prof. Hans-Joachim Schurek, Lingen-Ems
Sponsors – up to 500 Euros
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Dr. Berend-Tüge Berendsen, Mönkeberg
Heiko Flügel, M. Sc., Bad Soden
Dr. Jan Hilpert, Berlin
Prof. K.W. Kuehn, Karlsruhe
Prof. Klaus-Hinrich Neumann, Magdeburg
Dr. W. Scott Long, Connecticut Hospice, New Haven, CT
Prof. Klaus-Hinrich Neumann, Magdeburg
Dr. Karin Maass-Poppenhusen, Kiel
Sustainers – up to 250 Euros
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Dr. Anne Dörte Achtert, Berlin
Dr. Stefan Blaas, Regensburg
Dr. Judith Brandstätter, München
PD Dr. Giuliano Ciarimboli, Münster
Prof. Thomas Deller, Kronberg
Dr. Eva Handke, Hamburg
Dr. Irmtrud Jäckle-Meyer, Göttingen
Dr. Volkmar Lufft, Rendsburg
Dr. Rüdiger L. Prosst, Fellbach
Prof. Jörg Rademacher, Minden
Dr. Benjamin Schäfer, Bangor, Maine
Dr. Burkhard Schulte, Friesoythe
Donors – up to 100 Euros
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Dr. Jan Boublick, New York
Prof. Jürgen & Barbara Floege, Aachen
Dr. Karl Fryburg, Tucson, AZ
Dr. Dirk Hentschel, Harvard Medical School, Boston, MA
Dr. Anne Hofer, Tübingen
Dr. Robert Massey, Dean em, University of Connecticut, Farmington, CT
Dr. Johannes Richter, Göttingen
Dr. Felix Wedegärtner, Hannover
Corporate Sponsors & Foundations – up to 25,000 Euros
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Bayer Crop. Sciences, Monheim
Boylan Foundation, Rhinebeck, NY
B. Braun – Melsungen AG, Melsungen
Genzyme Corporation, Framingham, MA
S. Karger Publishers, Basel
Provena Covenant Medical Center, Urbana, IL
Boehringer Ingelheim Inc., Ridgefield, CT
Preussag AG, Hannover
Carl Duisburg Foundation, Hannover
Founding institutions:
Mount Desert Island Biological Laboratory
Who's Who in IALS
Officers
Hilmar Stolte, MD, PhD
Univ. Professor emeritus
President, BMEP & IALS
Hannover & Potsdam, Germany
Klaus Neumann, MD
Vice President IALS (Europe)
Professor of Medicine
Magdeburg, Germany
Benjamin Schäfer, MD
Northeast Cardiology Associates
Treasurer, BMEP USA, Inc.
Bangor, ME, USA
Robert Rich, PhD
Chairman of the Board, IALS
Professor of Law & Political Sciences
University of Illinois, Urbana, IL, USA
Raymond L. Williams, JD
Roy, Beardsley, Williams and Granger, LLC
Clerk, BMEP USA, Inc.
Ellsworth, ME, USA
Michael Wiederholt, MD
Univ. Professor emeritus, Freie Universität Berlin
European Representative & Trustee, BMEP Inc.
Administrative Offices
European Office
IALS / BMEP
Prof. Hilmar Stolte, MD
Medizinische Hochschule
Hannover
Carl-Neuberg-Str. 1
D-30625 Hannover
T +49 511 532 6662
F +49 511 532 6663
[email protected]
European Office
IALS / BMEP
Heidrun Stache
IALS
Kaiserstr. 15
D-32545 Bad Oeynhausen
Germany
T +49 5731 23941
F +49 5731 23942
[email protected]
IALS Office
Brandenburg-Berlin
Svetlana Orlova, PhD
IALS
Am Neuen Markt 6
D-14467 Potsdam
Germany
T +49 331 8170 701
F +49 331 8170 702
[email protected]
N. American Office
BMEP
Laurie B. Williams
56 Hancock Street
Ellsworth
ME 04605
USA
T +1 207 667 1920
F +1 207 667 5513
[email protected]
Supporters and Sponsors
IALS Life Sciences University Network
in public / private partnership:
GBM – Association for Innovation and Technology Transfer in Biomedicine, Ltd, Potsdam – Bad Oeynhausen
[email protected]
Editors:
Laurie Williams, B.A., Coordinator BMEP, USA
Holger Moerling, B.A., Photographs and Website
Sarah L. Kirkby B.A., Linguistic and Technical Coordinator
Thomas Bierbaum, M.A., M.Sc., Managing Director IALS
Heidrun Stache, Coordinator BMEP, Europe

BMEP Yearbook AY 2010/2011 (PDF 1.8Mb)

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