BMEP Yearbook AY 2009/2010 (PDF 1.7Mb)

Transcription

PRESIDENT’S ADDRESS
The IALS as an academy has its roots in the experience gathered by the BMEP (Biomedical Sciences Exchange Program Inc.)
in Salsbury Cove, Maine, USA. BMEP is an exchange program founded in 1979 by Prof. John Boylan M.D. of the Medical
School Farmington of the University of Connecticut (USA) and Prof. Hilmar Stolte of the Hanover Medical School.
John Boylan, Hilmar Stolte, Robert Massey
Since it was in founded in 1979, 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 ocean.
A core group of almost 700 participants has trained using the “Central European patho-mechanistic approach“, adopted via the
English “learning by doing“ approach, to include the new development from molecular biology to the Life Sciences. Unlike
other sciences, the life sciences are concerned with all aspects or manifestations of life – human and non-human. This raises
numerous issues beyond purely scientific questions: e.g. bioethical and human life related questions. Life sciences build a
bridge between sciences and the humanities, because as humans we are all immediately and essentially involved in the results
of the life sciences. New medical options, innovations in food technology and the diverse applications of bio- and gene
technology will increasingly and profoundly change our lives. These changes demand a new kind of education for those who
will lead medicine into the 21st century.
It is the mission of the “BMEP-Biomedical Exchange Program” to foster a new generation of medics and researchers making
the most of this fascinating development.
Prof. Hilmar Stolte, M.D.
President IALS & BMEP
University Professor em., Medizinische Hochschule Hannover
Distinguished Professor, Charité Universitätsmedizin, Berlin
N.B. A celebration to mark 30 years of BMEP/IALS will be held in Berlin on 10th/11th December 2010
Participants
Hilmar Stolte with some of this year's participants
Participant
Home University
Host University
Hug Aubin
Ruprecht-Karls-Universität
Heidelberg
Harvard-MIT
Cambridge, Massachusetts
Stefan Brauns
Charité Universitätsmedizin
Berlin
Harvard Medical School, Mass.
General Hospital
Boston, Massachhusetts
Torben Brod
Medizinische Hochschule
Hannover
Emory University School of Medicine
Atlanta, Georgia
Elena Chirvon
NRC Institute of
Immunology, Moscow
Hannover
Sebastian Darr
Hannover
University of Pittsburg, Medical School
Pittsburg, Pennsylvania
Mikhail Dinikin
St. Petersburg State Medical
Univ. of Acad. I.P. Pavlov
Hannover
Yulia Dinikina
St. Petersburg State
Medical Pediatric Academy
Hannover
Johanna Goldmann*
Freie Universität
Berlin
Stanford University, School of Medicine
Standford,Califonia
Pascal David Johann
Eberhard Karls Universität
Tübingen
Harvard Medical School
Childrens Hospital
Boston, Massachusetts
Ingolf Karst
Charité Universitätsmedizin
Berlin
Northwestern University
Chicago, Illinois
Anna Kern
Hannover
Russian Academy of Medical Sciences
St. Petersburg, Russia
Julie Kraas
Universität Hamburg
Harvard Medical School,
General Hospital,
Christian Matiaske
Hannover
Harvard Medical School
Brigham’s and Womens Hospital
Mariya Mollova
Hannover
Boston Children’s Hospital
Katharina Peter*
Hannover
Vanderbilt University
Nashville, Tennessee
Daniel Estévez Prado
Technische Universität
München
Yale University School of Medicine
New Haven, Connecticut
Ines Rudolf
Heinrich-Heine-Universität
Düsseldorf
Insa-Marie Schmidt
Hannover
Christoph Schünemann
Elena Widmann
J. W. Goethe Universität
Frankfurt
Tufts University School of Medicine
* Clerkship program
A Few Words from the Editor
The 2009–2010 Academic Year Program for BMEP was one of highs and lows. The number of students selected for the
program was higher than in many recent years, but the number of students who were able to attend the 2010 BMEP FORUM II
in Farmington, CT from April 9th to 11th was the lowest of my 10-year tenure as the United States Program Coordinator.
Many of the students who were in the United States had to return to Germany before the FORUM date, and one student had to
withdraw from participation in the FORUM due to emergency jaw surgery.
We had a full agenda planned for the day on Friday, 9 April, instead of the half-day that we had previously scheduled for the
first day of the FORUM. There were two alumni speakers, Dr. Benjamin Schäfer, who is now a cardiologist in Bangor, Maine,
and Dr. Claudia Hriesik, who is a surgeon practicing in Rochester, New York. We also had again our favorite medical historian
as a guest speaker, Ralph Arcari, Ph.D., from the University of Connecticut Health Center School of Medicine. Four of our
students gave their talks on Friday as well. The day also included a trip to the Hill-Stead Museum in Farmington.
The alumni guest speakers who were able to join us on Saturday were Dr. Elmar Burchardt, who was then in Ann Arbor,
Michigan, and who will now be working in the Boston area, and Dr. Thomas Schwaab, who is at the Roswell Park Cancer
Institute in Buffalo, New York, specializing in robotic surgery of the prostate. During the extra time that we had in the Saturday
schedule, Dr. Schwaab organized a trip for the students to the Mark Twain Museum in nearby Hartford. The day concluded
with our annual dinner at the Country Club.
As I look forward to my eleventh group of BMEP students arriving in the U.S.for the AY 2010-2011 (and attending the
FORUM, I hope), I continue to appreciate the great influence that the program has on its participants, and marvel at the
expanded opportunities that it brings to their professional lives.
Laurie B. Williams
U.S. Program Coordinator
BMEP, USA
TRANSATLANTIC BRIDGE
HUG AUBIN
E-Mail: [email protected]
Home Institution:
Faculty of Medicine,
Ruprecht-Karls-Universität Heidelberg
Host Institutions:
Center for Biomedical Engineering, Department of Medicine,
Brigham and Women's Hospital, Harvard Medical School,
Boston, MA
&
Harvard-MIT Division of Health Sciences and Technology,
Massachusetts Institute of Technology, Cambridge, MA
Research Mentor:
Ali Khademhosseini, Ph.D.
Personal Reactions to the U.S. Experience:
Boston! From an academic viewpoint it is simply amazing, home of Harvard, MIT, Tufts, Northeastern, BU and many more. So
many opportunities to attend top-notch seminars, participate in excellent workshops, and hear some unforgettable lectures…just
like being a child in a chocolate factory. The academic network, together with the existing brainpower and research facilities,
make up an unbelievably stimulating environment for doing research. However, Boston offers way more than dusty lecture
halls, nerdy students and famous professors. It’s a vibrant city with a high quality of life. From Harvard and Central Squares, to
Cambridge St., over the Charles River to Charles St., Tremont St., Newbury St., and down the Alley, everything is close by,
reachable by the T and full of charming cafés, good restaurants, great bars and clubs. The nightlife community is a mixture of
students, yuppies and a large European expat community that made me feel like doing an ERASMUS over again. New York
just down the coast all year around, Indian summer up north in the fall, and Cape Cod in the spring completed an awesome
experience.
Greatest Difficulties Encountered:
Getting the visa. Don’t expect everything to run smoothly just because you are part of the BMEP program. Try to personally
arrange for everything you need as soon as possible and be prepared to encounter some difficulties on the way.
Most Humorous Incident:
Too many to pick one…from not being able to shut off the smoke detector after the first time cooking in my apartment, even
after taking out the batteries; over drinking one beer with some Chinese colleagues at lunch and seeing them drunk in the lab
for the rest of the day; to meeting Katie Holmes and Tom Cruise while going for a run at the Charles River.
Helpful Hints for Future Students:
For students going to Boston: beers at Miracle of Science bar after work, gin and tonics at Middlesex on Thursday nights, expat
parties at the Liberty Hotel, and NYC, NYC, NYC!!!
Abstract on Research Topic – Hug Aubin
Title:
Directed 3D cell alignment and elongation in mircoengineered hydrogels
Authors & Institutions: Hug Aubin1,2, Ali Khademhosseini1,2 et al.
1
Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School &
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA
2
Introduction:
Organized cellular alignment is critical to controlling tissue micro-architecture and biological function. Although a multitude of
techniques have been described to control cellular alignment in 2D, recapitulating the cellular alignment of highly organized
native tissues in 3D engineered tissues remains a challenge, lacking a simple technique for microscale control of cell behavior
that is largely cell-driven.
Materials and Methods:
We encapsulated endothelial cells, fibroblasts, myoblasts and cardiac stem cells, chosen as model cell types for the potential
applications in vascularized, musculoskeletal and myocardial tissue engineering, in 5% (w/v) gelatin methacrylated hydrogels
patterning them into high aspect ratio rectangular 3D microconstructs of varying widths.
Results:
After 5 days of culture, cells encapsulated in 50 µm wide micropatterned hydrogels significantly self-organized into viable,
highly aligned microconstructs consisting of elongated, aligned cells throughout the entire gel thickness. Increasing
microconstruct width significantly decreased cell alignment and elongation up to random cell orientation in unpatterned
hydrogels, demonstrating that cell organization could be directed in 3D. MMP inhibition studies showed that ECM-remodeling
via MMP-2/9 activity played a crucial role in 3D cell organization. The presented system further demonstrated the potential to
engineer functional, macroscale 3D tissue constructs of user-defined size and shape with microscale control of cell elongation
and alignment through self-convergence of multiple, aligned microconstructs spaced in close enough proximity to merge
together.
Conclusions:
In this study we present a novel, simple and direct method to control 3D alignment and elongation of various cell types
encapsulated in microengineered hydrogels, demonstrating that cells with the intrinsic potential to form aligned tissues in vivo
will self-organize into functional tissues in vitro if confined in the appropriate 3D microarchitecture. The presented system may
be used as an in vitro model for investigating cell and tissue morphogenesis in 3D, as well as for creating tissue constructs with
microscale control of 3D cell alignment and elongation, that could have great potential for the engineering of functional tissues
with high degree of cell alignment and anisotropic function.
Note: Hug Aubin received funding from the DAAD (ISAP initiative) for his BMEP year in the U.S.
STEFAN BRAUNS
E-Mail:
[email protected]
Home Institution:
Department of Psychiatry and Psychotherapy,
Charité Universitätsmedizin Berlin
Host Institutions:
Athinoula A. Martinos Center for Biomedical Imaging,
Harvard-MIT Division of Health Sciences and
Technology & Massachusetts General Hospital,
Charlestown, MA
Research Mentors:
Randy L. Gollub, M.D., Ph.D., Associate Director, Psychiatric Neuroimaging Research Program &
Stefan Ehrlich, M.D., Postdoctoral Research Fellow
I have had a wonderful time in the United States. It was a big adventure, full of unexpected and completely unpredictable
experiences and many great new people. The first thing I have to mention is that I was very lucky to have a good doctoral thesis
project and support from the BMEP. I am very thankful to my supervisors Dr. Ehrlich and Dr. Gollub, who made it possible for
me to come to Boston. They both are excellent teachers and very efficient scientists. I could work in a very productive,
supportive and social environment.
Working at the Martinos Center was also a fun thing to do. I met many international scientists with whom I became friends and
with whom I shared much of my free time in Boston. I can only confirm what is described by all earlier generations of BMEP
participants. This city is amazing and has plentiful different cultural opportunities. It won’t get boring here! It was also a
valuable experience to meet Americans who are not in academia, and to discover cultural similarities and differences. For
example I have had some intense discussions about controversial political issues. Compared to reading about the USA from a
European newspaper point of view, my stay helped me a lot to better understand American politics.
Once you accept that this year is an investment in your future career and personal development, you will find it easier to spend
money on housing, traveling and many of the bars, restaurants and clubs you might want to go to. In addition there is always
the typical problem of Germans staying abroad: it was not possible for me to find good (but not expensive) bread. In order to
psychologically balance this I got addicted to good burger places and muffins.
Most Humorous (or ironic) Incident:
There was a highly unlikely situation when I was about to fly back home for Christmas. During the landing in Boston the
captain’s chair got broken. Air Canada tried to fix it, but failed, and after five hours of waiting, everyone had to rebook their
flights. A girl standing ahead of me in line wanted to go to Iceland. She made the mistake of booking a flight from Boston to
Paris with Air Canada and a close connecting flight to Reykjavik with Iceland Air (for which Air Canada was not responsible).
She got a new ticket to Paris that night, but it was clear that she would definitely miss her flight to Iceland. After rebooking my
flight, I was hoping to get my luggage back, but for some reason it took the airline another hour. While waiting for my
suitcases, I talked to a French guy, who wanted to go back home to Paris. Ironically he was also upset about his altered flight
plan. Air Canada rebooked his flight via Reykjavik, where he had to wait about 15 hours for his connecting flight to France!!!
• Craigslist for housing and bikes (which I would recommend in Boston)
• join the Facebook group Europeans in Boston (many nice activities)
• there are numerous possibilities to enjoy free concerts and music, for example in the Jordan Hall (symphony concerts)
or at Wally’s Cafe (Jazz Club)
• take the Megabus (and not the Chinabus) to NYC
• if you have the money - go to California for some days, when it is really cold in Boston (thanks to my 2 best friends in
Boston for our fantastic days in San Francisco!)
• if works seems too hard in the beginning, do not be discourages; probably it just needs some time to adapt to the new
environment
Abstract on Research Topic – Stefan Brauns
Title:
A common variant of DISC1 is associated with cortical thickness and neural efficiency
Authors:
Stefan Brauns, Randy L. Gollub, M.D., Ph.D. and Stefan Ehrlich, M.D.
Institution:
Athinoula A. Martinos Center for Biomedical Imaging, Harvard-MIT Division of Health Sciences and Technology &
Massachusetts General Hospital, Charlestown, MA
Introduction:
Disrupted in Schizophrenia 1 (DISC1) is a promising candidate gene for schizophrenia. Numerous studies have reported that
DISC1 is highly expressed during embryonic neurogenesis and plays a vital role in the growth of the embryonic and postnatal
brain.
The Phe allele of the DISC1 single nucleotide polymorphism (SNP) Leu607Phe has been associated with elevated risk for
schizophrenia, a greater severity of positive symptoms, and possibly even structural brain abnormalities.
Patients with schizophrenia show widespread reductions of cortical thickness. These abnormalities are highly heritable and may
therefore represent an intermediate phenotype of schizophrenia.
We tested whether cortical grey matter thickness is related to common variants of DISC1 in healthy subjects. We found an
association of Leu607Phe and cortical thickness in the left supramarginal gyrus, which is part of the inferior parietal lobule.
Because of the known role of the inferior parietal lobule in cognitive and executive functioning and the implication of the
frontoparietal network in working memory performance, we also tested the effect of this SNP on behavioral performance and
neural activity during a working memory paradigm.
Materials and methods:
We modeled the main effects of 5 DISC1 SNPs and 3 haplotypes on cortical thickness, using structural MRI and genotype data
from 96 healthy volunteers. All MRI data were analyzed utilizing an automated surface-based algorithm (FreeSurfer) to
estimate cortical thickness at 163842 vertices per hemisphere. In a follow up analysis we tested the effects of the Leu607Phe
SNP on average working memory accuracy (Sternberg Item Recognition Paradigm), as well as neural response to increasing
working memory difficulty using linear regression analysis. Neural response was modeled for right and left DLPFC as well as
the left supramarginal gyrus.
Results:
Carriers of the Phe allele of Leu607Phe showed reduced cortical grey matter thickness in an area corresponding to the left
supramarginal gyrus. A haplotype (Leu607Phe, rs11122359: TG) including the same risk allele was also associated with
reduced cortical grey matter thickness in the left supramarginal gyrus. At the behavioral level Phe allele carrier seemed to have
reduced average accuracy when performing the SIRP task. However, Phe allele carrier recruited significantly more neural
resources in the left DLPFC during the same working memory paradigm
Conclusion:
The supramarginal gyrus is known to be an essential part of the heteromodal association areas, related to positive symptoms
and working memory functions. Numerous studies now support a pathophysiological role of the inferior parietal lobule as a
component of an impaired frontoparietal network. Parietal regions were associated with positive symptoms of schizophrenia, in
particular auditory hallucinations. Intriguingly, variants of DISC1 including the Phe allele of Leu607Phe have also been
associated with hallucinations and delusions. Thus, our finding might provide a potential link between both observations.
Interestingly, our study could also detect neural inefficiency during a working memory paradigm in prefrontal regions; that is,
Phe allele carrier needed to devote greater cortical resources to perform the same task in the left DLPFC compared to Leu/Leu
homozygotes.
Note: Stefan Brauns received partial funding for his BMEP year from DAAD (ISAP initiative).
TORBEN BROD
Home Institution:
Medizinische Hochschule Hannover
Host Institution:
Division of Cardiology, Emory University School of Medicine
Atlanta, GA
Research Mentor:
David G. Harrison, MD
I had a great time in the US! Atlanta, although not very pretty itself, offers basically everything one can ask for: two great
universities, famous sport teams (Hawks/Falcons), lots of clubs, bars and people from almost everywhere around the world.
Emory Medical School is a great institution to study at! Sitting in a brand new lecture hall with enthusiastic professors as your
teachers, I immediately felt home. Also in the lab, everybody was more than happy to help me with any problem, scientific or
not. Even though not all my experiments worked out perfectly right away, I had the chance to learn lots of techniques and
acquire new knowledge in various aspects of cardiovascular medicine.
I really enjoyed my time in the US and will be back at the same institution for clinical training next year. Also this stay enabled
me to get to know lots of interesting people, some of whom I can call my friends now. I can only encourage every medical
student to participate in this great program!!
The visa! Since Emory didn't have any BMEP students for a few years, nobody really knew how to handle this issue at first.
Making some phone calls, however, helped out a lot, so I finally managed to get the appropriate visa for my stay.
Once I arrived, everything worked out perfectly and I didn't experience any other major problems.
There were quite a few funny/entertaining incidents during my stay at Emory!
When looking for a room, not knowing what to expect when it says LBGT-friendly... Being offered a room and shared
bathroom with a 90-year-old lady. Going to the American Heart Conference with my Mentor and lots of cardiology Fellows
and partying it up in Orlando for 5 days including a trip to Cape Canaveral, just to name a few!
• Start your visa application as soon as possible!! (If possible, right when you get the confirmation from your host lab)
• Get an account from the DKB (DKB-Cash) (there's no fee for drawing money worldwide!)
• Check out craigslist and in Atlanta also the Emory Off-Campus- Housing webpage for cheap rentals or sublets.
• Contact former BMEP students that spent time in your city.
• Get a bike or use the school’s free bus system instead of buying a car!
Abstract on Research Topic – Torben Brod
Title:
Role of Tetrahydrobiopterin in T cells
Authors:
Torben Brod, Wei Chen, David G. Harrison
Institution:
Division of Cardiology, Emory University School of Medicine, Atlanta, GA
Introduction:
Tetrahydrobiopterin (BH4) is an essential cofactor for the nitric oxide synthases (NOS) and represents a critical determinant of
NO production. In the case of BH4 deficiency the NOS enzyme is uncoupled, leading to excess generation of reactive oxygen
species, especially O2-.
Recently, our lab found that phosphorylation of GTP cyclohydrolase-1 (GTPCH-1), the rate-limiting enzyme for BH4
biosynthesis, increases its activity and BH4 levels in endothelial cells. The aim of the current study was to determine if this
process also occurs in non-endothelial cells.
Methods & Results:
Thus we stimulated T cells both in vitro (anti-CD3) and in vivo (OVA immunization in OT2 mice). Naïve T cells had nearly
undetectable levels of BH4 and minimal expression of either endothelial or inducible NOS. Anti-CD3 stimulation robustly
induced T cell eNOS and iNOS and increased biopterin from near undetectable levels to 5.4 pMol/mg protein. Biopterin
induction was similar in CD4 and CD8 cells. Western blots showed that this was associated with GTPCH-1 phosphorylation at
S72. Pharmacological inhibition of casein kinase II prevented GTPCH-1 phosphorylation and blunted the increase in T cell
BH4. Inhibition of GTPCH-1 with diaminohdroxypyimidine (DAHP, 500 µm) prevented T cell BH4 accumulation and
increased T cell superoxide produciton, which was dependent on uncoupling of both eNOS and iNOS. GTPCH-1 inhibition
also promoted TH2 polarization in memory CD4 cells. OVA immunization in vivo confirmed a marked increase in T cell BH4.
Conclusions:
T cell activation is associated with GTPCH-1 phosphorylation, which increases GTPCH-1 activity and biopterin production. In
inflammatory settings where BH4 oxidation is favored, this could modulate T cell function.
Note: Torben Brod received funding for his stay from the DAAD (ISAP initiative).
SEBASTIAN DARR
Home Institution:
Hannover Medical School, Germany
Host Institution:
University of Pittsburg Medical School, Pittsburg, Pennsylvania
Research Mentors:
Prof. Hans Harald Kreipe, Chairman, Department of Pathology, Hannover Medical School, Hannover
Prof. Stefan Duensing, PI, Hillman Cancer Center, Pittsburgh, PA
Prof. Karl Munger, PI, Channing Laboratory, Harvard Medical School, Boston, MA
I really like the U.S. a lot. I always did. As a country full of diversities it is really hard to find some prejudices against this
country that are definitely true. It is simply not possible to say much about “the USA” or “the Americans” in general because
the country is extremely big and colorful. In the same way as it is not really adequate to compare someone from Kiel with
someone from Augsburg, it is not with someone from Massachusetts compared to someone from Texas.
Especially between you and the people you are interacting with on a research scholarship, there is not much diversity, as they
are academics as well, and very open minded, from what I can tell from my experience.
For me, it was way more fascinating to find out how much of a German I really am. To get some feedback on your values and
behavior is really fascinating and sometimes I laughed on the inside when I realized how well I was fitting in with some
clichés.
In order to complete some experiments I had to spend some time in our cooperating lab at the Harvard Medical School in
Boston. Although I had great support from both my PIs, it was very, very difficult to organize the visa transfer from Pittsburgh
to Boston. Especially since the Brigham and Women’s Hospital in Boston does not accept foreign medical students any more if
they don’t have a bachelors or masters degree. There is a possibility to get an equivalent for our German medical “Physikum”
but still, it remains unclear whether this will be accepted or not by the officials. Always make sure that your visa status is 200%
clear, appropriate for what you are planning to do, and supported by the official institutions, before you start working on a
project.
One morning I was very focused on my bench work and my American colleagues asked me why I was so quiet. I told them I
was highly concentrated on this extraction procedure. We all laughed a lot when I realized that this “false friend” is sometimes
true for orange juice but never for people.
- When searching for a room on craigslist.com always ask for pictures and make sure that there are no hidden fees and
that you can leave whenever you want.
- Do not drink alcohol in public.
- The MLP credit card allows you to get cash at all ATMs without any fees as long as you are getting more than 100
Euros in US$.
- Best sandwiches in Massachusetts: both “Darwin’s” in Cambridge
Abstract on Research Topic – Sebastian Darr
Title:
Requirement of tripeptidyl peptidase II activity for c-Myc induced centrosome duplication errors.
Authors:
Duensing S. 1, Darr S. 2, Munger K. 3
Institutions:
1) University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA
2) Hannover Medical School, Hannover, Germany
3) The Channing Laboratory, Brigham and Women¹s Hospital, Boston, MA
Introduction:
Overexpression of the c-Myc oncogene in human cancers is frequently associated with genomic instability including gains and
losses of whole chromosomes. Here we show that c-Myc can rapidly cause mitotic infidelity by inducing centrosome and
centriole duplication errors. In normal cells, centrosome activation requires both activation of cyclin/cdk2 complexes and
ubiquiting/proteasome dependent proteolysis. C-Myc therefore rapidly stimulates aberrant centrosome duplication by
dysregulation of the G1/S transition of the cell cycle. However, the proteasome machinery has been found to be functionally
impaired in c-Myc expressing cancer cells.
In order to generate U2OS cells containing an inducible c-Myc plasmid, the retroviral vector c-mycERTM was transfected into
these cells. Four puromycin resistant clones were selected. The fusion of ER and myc was activated by adding 4hydroxytamoxifen to the media. The expression of c-MycER proteins was determined by western blotting of the lysates.
U2OS cells were grown on cover slips to 60% confluency and transfected with the indicated plasmids, c-Myc, TPP2, shTPP2,
siTPP2, and dsRed as a transfection marker. Cells were stained with a polyclonal centrin antibody and percentage of cells
displaying supernumerary centrosomes were detected by immunofluorescence microscopy.
The human B-cell lines BL2, BJAB and DG25, that are stably overexpressing c-Myc, were treated with the selective inhibitor
butabindide and harvested after the indicated time points for microscopic analysis of centrosome abnormalities.
Results:
We discovered that c-Myc induced disruption of centrosome homeostasis critically depends on the activation of alternative
proteolytic pathways involving the oligopeptidase tripeptidyl peptidas II (TPP II) in a rate limiting manner.
Conclusions:
Subversion of TPP II activity using the selective inhibitor butabindide not only abrogates centrosome duplication errors induced
by acute overexpression of c-Myc but also effectively restrains the growth of Burkitts lymphoma cells with constitutive c-Myc
activation. This work will be the basis for future studies to develop targeted therapies in human cancer the overexpressing cMyc.
Note: Sebastian Darr received financial support for his time in the U.S. from the German National Academic Foundation.
JOHANNA GOLDMANN
Home Institution:
Freie Universitat, Berlin
Host Institution:
Stanford University,
Palo Alto, CA
Research Mentor:
Prof. Bingwei Lu
Having lived in the U.S. for a couple of years during High School, and having visited family here for more than 10 years, the
U.S. was not exactly foreign to me. So when I arrived in Stanford I thought I knew what was coming – and found myself
surprised in many ways. Stanford University, located near San Francisco in the Bay Area, on a huge campus (second only to
Moscow, as was pointed out to me on several occasions,) is a vibrant place. On a normal “school-day” the entire campus is
crawling with people, and it’s is quite common to nearly be run over by a student on a bicycle trying to make it to class. Most
of life at Stanford takes place on the campus: meetings, discussions and presentations of all kinds – it seemed that on almost
every piece of grass, in every corner and room something was going on. It is rare to find a place that has so many of the world’s
finest in one place – and that was quite inspiring. Just when going for a cup of coffee, I often found myself engaged in
discussions ranging from the economical and political implications of Obama’s health care plan, to whether or not his getting
the Nobel Peace Prize was justified, to particle physics and the LHC, to long discussions about my immediate work.
I also found myself to be very lucky to be working with Professor Dr. Bingwei Lu, who did a fantastic job as a supervisor.
Every week on Friday we met in his office and discussed my work and results of the previous week. While I was rather nervous
the first time, I soon found these meetings to be an integral part of my work, as I always learned a tremendous amount from
discussing my work with him. It was great to know that Dr. Lu took me, and my work, seriously, and he invested a great
amount of time and work in me – something that inspired me to give my best, and allowed my work at Stanford to become a
challenging but wonderful and defining experience in my scientific career.
Stanford being a private university and rather expensive, even by U.S. standards, maybe it should not have been a surprise that
“Money was in the Air”. Yet, I was quite surprised to see just how different student life here was from Germany. Students
driving around with BMWs and going out for every meal was the rule rather then the exception – compare that with Berlin,
where it is rare to have car, and if one has, it is more likely to be a 1987 VW than a 2009 BMW. It was quite a change, a change
that went far beyond day-to-day activities (and expenses), and there was a whole new attitude I encountered – an attitude (of
course not shared by everyone in Stanford) where money was success. This was very different from the view I grew up with,
and one – even after my time at Stanford – with which I cannot find myself in agreement.
One weekend my colleague, George, and I decided to drive down to San Diego. In San Diego, George decided to jump off a
cliff, which, unfortunately, resulted in George breaking his arm in several places. Soon it was clear that he would need surgery.
In the hospital, while preparing George for surgery, the doctor noticed that I, and his twin Abe, were joking with George, trying
to ease the time before surgery. After talking to him for a while, we found out that he, too, had attended Stanford. About 10
minutes later the surgeon came by, looking at us dead seriously, and said, “ Oh, George, there is something you should know –
we just talked to the insurance company and your insurance no longer covers anesthesia, so you will just have to bite down on a
stick instead!”
Having dual citizenship, I was lucky enough not to have to get a visa, which appears to be a major hurdle for many BMEP
students. But, of course, I also encountered a few difficulties while in the U.S. While it may be said that Germans are known for
their bureaucracy, I found the bureaucracy – at least at Stanford – to go far beyond any form I have encountered in Germany! I
can only advise you to bring any official papers, degrees etc. I had to hand in my Abitur Zeugnis, (even though at that point I
had already been admitted!), and lots and lots of time and patience!
Note: Johanna Goldmann received financial support for his time in the U.S. from the German National Academic Foundation.
PASCAL-DAVID JOHANN
Home Institution:
Eberhard-Karls University Tuebingen
Host Institution:
Childrens Hospital Boston, Harvard Medical School
Research Mentors:
David Williams, MD, Children’s Hospital Boston;
Anja Tröger, MD
Personal Reaction to the U.S. Experience:
Passing one academic year of research in the US has shown to be a really rewarding experience for me- both in professional
and in personal terms. It is hard – if not impossible- to find a city were so much scientific creativity is gathered in one place.
The atmosphere in the laboratory was relaxed and I was lucky to find colleagues who were always ready to provide helpful
hints for the experiments. The almost stereotypical friendliness of the people in the U.S. (that is often connotated with a certain
superficiality) facilitates first contacts a lot. However, going beyond shallow small-talk towards a longer-lasting friendship is
probably even harder with Americans than with Germans.
Boston has often been described has very European, which to an extent is true. In my view, many Bostonians combine an
American open-mindedness with a European pride in culture and tradition.
Still, there are some aspects of American society I did not come to appreciate: the low level of solidarity in American society,
reflected in the zealous protests against Obama’s health care reform, is something I never fully grasped.
Definitely not the visa process, which was easier than first anticipated. As in most laboratory settings, getting the experiments
started and succesfully finished proved to be the most difficult task.
I do not remember a particular event, however there were a lot of funny incidents caused by “Babylonic language confusions”
in the lab.
- Don’t worry too much about the visa
- If you find yourself in Boston, take advantage of the various cultural opportunities in the city.
- Wear sunscreen!
- Contact me anytime if you have any questions regarding your time in Boston.
Abstract on Research Topic – Pascal-David Johann
Title:
Rac and RhoH GTPases in the development of acute lymphatic leukemia
Authors:
Pascal Johann, Anja Tröger, MD and David Williams, MD
Institution:
Children’s Hospital Boston, Harvard Medical School
Introduction:
GTPases are class of enzymes that cycle between and active GTP bound state and that are inactivated upon GTP hydrolysis.
Inactivated enzymes are sequestered in the cytoplasm.
Recent findings suggest a role for Rho and Rac GTPases in different neoplasias: RhoH has been found at increased levels in
CLL samples and RhoH (-/-) mice develop leukemia more slowly than their littermates1.
Similarly, Rac GTPases have been identified as potential targets in AML and are believed to mediate crucial steps in bcr-abl
dependent leukemogenesis2.
The aim of this pilot study was to determine if RHOH and Rac GTPases can be targeted pharmaceutically by NSC. This
compound has in vitro effects against different GTPases by blocking the GTP binding groove. However it remains poorly
defined which Rac GTPases are affected.
To investigate if a depletion of Rac or RhoH GTPases leads to an increase in the apoptotic rate of different ALL cell lines,
lentiviral vectors harbouring shRNA against different Rac proteins were constructed.
The efficiency of the respective shRNA carrying lentiviruses was tested in 32D cells, expressing human Rac proteins.
Leukemic cell lines were infected with viral constructs against the Rac and RhoH proteins and Apoptosis stains were performed
at day 5, 6 and 7.
To determine which apoptotic pathways are involved Western Blot analysis will be performed.
Results:
Preliminary results show an increase in the apoptotic rate of NSC treated leukemic cell lines. Apoptosis of ALL cell lines
seems to be increased after treatment with the viral constructs.
The results of the lentiviral infections and the Western Blot detection are still pending.
References:
1. Sanchez-Aguilera A, Rattmann I, Drew DZ, Muller LU, Summey V, Lucas DM, Byrd JC, Croce CM, Gu Y, Cancelas JA,
Johnston P, Moritz T, et al. Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia.
Leukemia 2010;24:97-104.
2. Muller LU, Schore RJ, Zheng Y, Thomas EK, Kim MO, Cancelas JA, Gu Y, Williams DA. Rac guanosine triphosphatases
represent a potential target in AML. Leukemia 2008;22:1803-6.
Note: Pascal Johann received partial funding by the B.Braun Melsungen Fellowship for his stay in the US.
INGOLF KARST
Home Institution:
Charité
University Hospital Berlin
Host Institution:
Feinberg School of Medicine, Northwestern Memorial Hospital,
Prentice Women's Hospital, Chicago, IL
Research Mentor:
Ellen. B. Mendelson, MD, FACR
Chicago is a very decent place to work. And it is a city of extremes. During winter it gets really cold, at least for MiddleEuropeans, and during summer it is said to be very hot. It is called the “Windy City” and also the “most American of big
cities”. Two blocks from my apartment I can reach the beach, which is wonderful - and that in the middle of downtown in the
largest city in the Midwest.
Different from other cities, there is the combination of a metropolitan and convenient lifestyle, the possibilities of such a big
city, and living like at the sea, even though it is a big lake. Every time you will have a nice small talk with someone. You will
meet a lot of people who are interested. Different is the speed. That is often nice and often restless. At work you will probably
face challenging moments with bureaucracy.
I cannot say how much it means to me to be part of the Breast Imaging Section, NMH, Chicago, under the leadership of Ellen B
Mendelson, MD, coexistently my PI. It became family for me. It changed my life. I cannot even think about leaving it.
One of the challenges of this program is that you cannot live only on the stipend it provides for you. That can mean that you
have saved money before or get a loan or other funding. But in my opinion it is worth every cent. If you can afford it and you
find the right time in your studies or carrier to do it, then go for it and apply.
Special for me is to be part of new innovations. Therefore, I stood in line for the Apple iPad - despite that I normally hate to
wait standing in lines. It was a long time ago that I did it voluntarily. For the Americans it does not seem to be such a big thing as it was not for me this time.
As a mindset, which it is, the BMEP program is one of the best things you can do in your lifetime. You will learn and know
things you would never learn without this program. You will get in touch with so many interesting people and things that you
probably never thought of. Sometimes it is like a dream and sometimes it is challenging. You will learn about the similarities
and differences in culture and work.
Dr. Stolte, Laurie Williams, Dr. Mendelson thank you so much!
Abstract on Research Topic – Ingolf Karst
Title:
An integrated, multidisciplinary Evaluation-System in interdisciplinary breast cancer treatment.
Authors:
I. Karst, MD; E. B. Mendelson, MD; U. Bick, MD
Institutions:
Northwestern University, Department of Radiology, Breast Imaging Section, Chicago, IL, USA & Charité, University Hospital
Berlin, Germany
Introduction:
Clinical outcome in patient care crucially relies on the diagnostic skills of the clinical team. In the diagnostic evaluation of the
breasts, the diagnostic accuracy requires cooperation of the radiologists, gynecologists, pathologists, and oncologists involved
in patient management.
We developed and adopted an integrated, multidisciplinary system that allows preparing and conducting interdisciplinary
conferences and treatment. The information comprises mammography, US, MRI, details of the imaging-guided procedures, and
related pathologic sections in addition to patient data. At meetings and conferences the cases can be discussed and analyzed.
The system thus enables compilation of well-documented, pathologically-proven cases over an extended period of time, thus
enabling correlation of diagnostic and therapeutic approaches with the outcome of treatment.
Results:
We expect that the interdisciplinary communication and documentation will improve diagnostic accuracy by establishing
concordance of radiologic findings with pathology reports and the interventional and/or intraoperative findings in a single
system. The statistical evaluation of the results awaits retrospective review of the project´s goals after at least a year of use of
this system.
Conclusions:
This project is a work-in-progress with the expectation that this multidisciplinary clinical system will be able to help to improve
the quality and cost effectiveness of breast cancer diagnosis and treatment.
Note: Ingolf Karst received some funding for his BMEP time in the U.S. through a bioinformatics grant from the B. Braun
Melsungen Fellowship
JULIE KRAAS
Email: [email protected]
Home Institution:
Universitätsklinikum Hamburg Eppendorf
Host Institution:
Harvard-MIT Division of Health Sciences and Technology
Center for Laryngeal Surgery and Voice Rehabilitation
Massachusetts General Hospital, Harvard Medical School, Boston, MA
Research Mentor:
James B. Kobler, Ph.D.
Harvard Medical School- the wonderland for research and medicine. It was always my dream to spend some time at this
outstanding institution. I couldn’t believe it when my plane didn’t land at Logan Int. Airport, but in the middle of Connecticut,
due to a thunderstorm in Boston. Is it so hard to get here? Yes, but once you have arrived you become a member of this big
community. And everybody is so proud of it. It took me some time to accept this idea of elite; but once I did, I had an
outstanding time: I met people from all around the world, I made friends, and I found a new inspiring way to see medicine.
Harvard’s brainpower is unbelievable!
I was lucky to live with wonderful American flatmates in Cambridge. They showed me a life outside the lab and the MGH.
There are so many students in Boston- it’s really not hard to meet interesting people! Nightlife is not Berlin, Paris or New York.
But Boston is beautiful - a perfect city!
I was happy to travel with my department to a Conference in San Diego. It was my first time in California. Wow! I couldn’t
believe how different life is on the West coast. You should try to discover as much outside the lab as you can!
If you are lucky and you have the right insurance you are allowed to do “hands-on” medicine. Great to see another kind of daily
life at the hospital (starting at 6 am…). Teaching plays a huge role, and is among the best I have ever experienced!
Greatest Difficulty Encountered:
Do you have problems getting the famous DS2019? Rest assured: you are not alone. The MGH is extremely strict dealing with
this type of visa. If you’re unlucky like me, you have to “buy” the administrative work from an organization specialized in this.
But: it’s worth it! Once you have all this in your pocket you shouldn’t be afraid of the Embassy part in Berlin: the interview is
nothing compared to the BMEP interview and they treat you like sugar.
There is only one thing my research mentor loved more than his job: free lunch. The free lunch at the MGH is basically a lousy
sandwich and a soft drink. Not very attractive. But he always tried to motivate the people in the lab to join him on his journey
to a new “free-lunch destination”. One day my mentor announced that the Nobel Prize winner Jack Szostak was holding a
speech - free lunch included. It was not hard to find people to join him: we arrived with 10 scientists at the conference room,
got the lunch box and took a seat in the third row. The speech started. It was not Mr Szostak but the Grand Rounds of the
oncology department. You can imagine the amusement of 10 scientists following 1 hour of cases about colorectal carcinoma.
• Sports are the best way to get in touch with other people! Americans love sports!
• Become a member at the Community Boating house: 100 ft away from the MGH you can rent boats, learn sailing, or
make a weekend trip. Bring your German Sailing Licence if you have one - it helps you to skip some training lessons.
• Weekend in New York: Take the Greyhound/Peter Pan Bus: But be aware: They sell endless tickets for one bus! Pro:
you can catch a bus earlier or later. Con: Your seat in the bus is not guaranteed. First come - first served…
• Get a credit card at the Bank of America - even without a social security number. Otherwise people look at you like a
criminal when you show up with $200 cash.
• Get an American driver’s licence: In Massachusetts the German driver’s licence allows you to get an American
driver’s licence without any tests, only some paperwork. With the American driver’s licence it is much easier to enter
a bar and drink a beer. And your passport with your holy visa can stay at home.
Abstract on Research Topic – Julie Kraas
Title:
Ex-Vivo Canine OCT imaging. Application of an Ex-Vivo non invasive imaging tool (Optical Coherence Tomography) in
larger mammal comparing biomaterials
Author:
Julie Kraas
Institution:
Massachusetts General Hospital – Harvard Medical School, Boston, MA
Introduction:
From a person's initial cry to his final words, the vocal folds probably sustain the most long-term, soft-tissue trauma of any area
of the body. Average conversational pitch frequencies for normal voices are 200 Hz for women and 120 Hz for men, which
match the number of collisions per second of the vocal folds and are accompanied by substantial shear stress. Although nearnormal conversational voices can be achieved in the phonosurgical management of early glottic cancer, there are still acoustic
and aerodynamic deficits in vocal function that must be better understood to help further optimize phonosurgical interventions.
Injecting fat into the vocal fold is a common way to improve vocal fold pliability where there is stiffness of phonatory mucosa.
Fat is typically absorbed in some months and is has a very unpredictable outcome. Looking for a material that is not absorbed
and fulfils the characteristics of the lamina propria of the vocal folds is a big challenge.
Study design:
Ex vivo study using excised calf larynges testing different biomaterials
Material and Methods:
Hyaluronic acid (HA) and dextran where chemically modified and subsequently crosslinked via formation of hydrazone bonds
in phosphate buffer. Swelling ratios, degradation, and compressive moduli of the resulting hydrogels where investigated. Those
gels were injected into excised calf larynges. These larynges were imaged with OCT.
Preliminary Results and Discussion:
It was found that the different hydrogels have a great impact on the vocal fold characteristics of the phonatory mucosa. OCT
imaging is not only useful to confirm the presence of hydrogel implants but can help to juge other criteria as stiffness and
pliability.
The results suggest that the HA-dextran hydrogel matrices can be further developed for application of vocal fold tissue
restoration.
Further data analysis still needs to be done before final conclusions can be drawn.
Note: Julie Kraas received financial support from the B. Braun Melsungen Fellowship for her BMEP time in the U.S.
CHRISTIAN MATIASKE
Home Institution:
Medical School of Hannover, Hannover, Germany
Host Institutions:
Brigham & Women’s Hospital, Boston, MA
and Faulkner Hospital, Jamaica Plain, MA
Research Mentor:
Dirk Hentschel, MD, Nephrologist,
Renal Division, Brigham & Women’s Hospital,
Harvard Institutes of Medicine, Boston, MA
The first weeks in US were quite different, if you compare it, for example, with a trip to Asia. On the one hand, you are still in a
‘western country’ - on the other hand, the culture, everything you see, is so overwhelming. This started with my first visit to a
common supermarket - everything is bigger and after a while I learned to look exactly on packages to see what is in it. You can
buy lots of very tasty stuff, but is it healthy??! The U.S. is unbeatable in variety of ice-cream, wonderful…yummy.
Another very big difference is the distances between places - in some places you need a car, no way to go from A to B without
it. In Boston you have the advantage of a public transportation system, even if the MBTA isn’t the fastest, especially in the rush
hour. NYC in comparison has a very good public transportation system. You do not need a car there.
Most of the people I met were very friendly to me and all had a warm ‘Welcome’ on their lips. Especially in the facility and
hospital where I was working, the people were easy to get along with. Outside of the lab/ hospital, it was sometimes more
difficult.
The healthcare system of the U.S., especially in the time of change, when Barack Obama tried to reform the healthcare system
and the insurance system, was very interesting. It was also interesting to see the sometimes quite radical opinions from his
opponents, and very quickly I recognized that in Germany we do not have a bad healthcare system.
Boston is not the cheapest city, but a city in which you can have a quite good life - lots of green, the ocean directly in front of
your door - NYC not very far away. It was a good way to start a U.S. experience, without getting shocked by the differences
between cultures. For research, in my opinion, Boston is one of the top cities.
We/I tried to get a kind of working visa, but there were several problems, mostly with BWH and Harvard University. If you do
not have an actual degree, which means a degree accepted in the U.S. (College or University), the International Office of BWH
or any other institution related to Partners HealthCare will not give you the sponsoring form that you need to apply for the J1
visa. They have increased the regulations for sponsoring in the last 2 years enormously. The problem was that without the J1
visa I was not allowed to work directly with a patient. For a clinical trial, this was kind of difficult. If you only want to do some
research in a lab, a B1 visa is fine and will work.
When I did one of my first runs through Somerville, where I lived for the first weeks, I was attacked by something like a
groundhog. It happened in the early evening. The sun was going down, but it wasn’t dark - and suddenly something jumped out
of a bush, so I was jumping, too. My heart was beating… but after all it was quite funny!
The most helpful hint which I can give to future students is to get information and to ask, ask, ask. Don’t give up if someone
doesn’t know something, or if someone says ‘No’ to something the first time. Pre-information about the facility and the
organization is, I think, 50% of your trip and will bring a successful ending.
Sometimes you need more time for ordering or for getting something - so you have to accept this. The easiest way not to have
the visa problems that I had is to start a research trip for clinical studies after finishing the final exams. Then you are on the safe
side. Or you can choose a lab-only research experience.
Abstract on Research Topic – Christian Matiaske
Title:
Dialysis access in the U.S. – is higher flow the detrimental factor?
Authors:
Christian Matiaske(1,2), Emily Pally(1), Jan T. Kielstein(2) and Dirk M. Hentschel(1).
(1) Medicine, Renal Division, Brigham and Women's Hospital, Boston, MA
(2) Nephrology, Medical School Hannover, Hannover, Germany
Institution:
Brigham and Women's Hospital, Department of Medicine, Renal Division, Harvard Institutes of Medicine, Boston, MA
Introduction:
Vascular access is the Achilles' heel for hemodialysis patient care. In the United States, the prevalence of autogenous accesses
has increased in the wake of Fistula First from 24% in 2000 to 52% in 2008. However, there is much debate about the quality of
these accesses. European studies of success of fistula creation and frequency of use often find much different results than their
U.S. counterparts. A defining character of dialysis accesses in European studies is that the majority of them are located in the
forearm, with potential for dual outflow through upper arm cephalic and basilic veins and subsequent low access pressures. We
aimed to determine the frequency of the location of dialysis accesses in a U.S. dialysis population and measure access flows,
which in setting of stenosis, would translate to higher intra-access pressures.
All patients of our institution’s outpatient dialysis unit where characterized regarding type (autogenous versus
prosthetic/biograft) and location (forearm versus upper arm). All patients referred to our interventional nephrology service with
access dysfunction underwent access flow measurements before and after angioplasty using a Transonic flowmeter.
Results:
At the time of evaluation 86 of 102 patients were using a graft or fistula for dialysis. Of 22 prosthetic or biograft accesses, 8
were in the forearm with arterial anastomoses at the elbow in 7 and one at the wrist. 14 accesses were in the upper arm with all
but two arterial anastomoses at the elbow. Of the 64 autogenous accesses 20 were in the forearm and 44 in the upper arm.
During the study period from May 2009 to January 2010, 101 patients underwent angioplasty with measurements of pre- and
post-angioplasty dialysis access flow. Mean post-angioplasty blood flows were 1260ml/min in the forearm prosthetic accesses
(n=7) and 1430ml/min in the upper arm prosthetic accesses (n=10), 1260ml/min in forearm biograft accesses (n=10), and
1260ml/min in upper arm mixed-autogenous-interposition biograft accesses (n=7). Forearm autogenous access mean blood
flow was 845ml/min (n=11) and upper arm autogenous access blood flow was 1580 ml/min (n=56).
Conclusions:
Upper arm accesses are more prevalent than forearm accesses. In particular, upper arm autogenous accesses outnumber forearm
fistulas 2:1. Access flow is highest in upper arm autogenous accesses, over 85% higher than average forearm autogenous access
flow. This increase in flow has consequences for intra-access pressure dynamics if stenoses develop and development of
stenoses themselves may be affected.
The complete work on the study is not yet completed.
Note: Christian Matiaske received a scholarship from the DAAD (ISAP initiative) for his BMEP time in the U.S.
MARIYA MOLLOVA
E-Mail: [email protected]; [email protected]
Home Institution:
Hannover Medical School
Host Institution:
Harvard Medical School, Children’s Hospital,
Boston, MA
Research Mentor:
Prof. Bernhard Kuhn, M.D, Associate Professor in Cardiology
My advice to all new BMEP applicants: if you have the chance to travel, seize the opportunity! Studying in different countries
is an invaluable experience-it broadens your horizon and makes you learn about life. The 9 months I spent in the United States
definitely changed my perception of science, medicine and life in general. I was ready to face new challenges and the idea of
going abroad was appealing to me, since I always wanted to gather some experience in a country with a completely different
educational and healthcare system, like the USA.
My scientific fascination with regenerative cardiology led me to Dr. Kuhn’s lab at the Children’s Hospital Boston. My PI was
not very worried by the fact I had never worked in a lab before and after a short period of training I became a full-time
researcher in the lab, with my own responsibilities and my own project. It soon became clear to me that if I wanted to achieve
something meaningful in a highly competitive field, I would have to be very convincing– hard work (irrespective of late hours,
weekends or holidays) was self-explanatory, imagination and creativeness were welcomed, dedication and pro-activeness were
mostly appreciated; a combination of them all paid off in the end.
I had the chance of working in a great lab, with fantastic people from all over the world. It did not take us long to become
buddies and have a lot of fun, regardless of whether we were at work or not. Even if you are a busy researcher, your time
management still depends entirely on you – so, if you are smart, flexible and effective enough, you can really enjoy yourself.
Boston is a great city, but the United States has a lot more to offer than that; I literally spent every free minute in travelling
around this beautiful country- a golden autumn in Maine, a shopping marathon in NY, a sightseeing tour in DC or a romantic
Californian sunset - America has a huge repertoire and can please every taste.
Unfortunately, Boston is an expensive city. Due to the fact that the numerous colleges and universities there attract students
from all over the world, real estate agents have learned to make a lucrative business out of this; living areas are dense; quality is
poor; prices are high.
I remember standing on the floor of our research unit, explaining feverishly to my boss how much I had to work over the
weekend (which I did, in the mornings!), when a Ph.D. from a neighbor lab passed by and said to me: “By the way, I saw you
at the Christmas party yesterday - you are a good dancer!” Obviously, my cover for the previous night was ruined. My boss,
who was clearly amused by my embarrassment, but nevertheless pleased with my recent experiments, commented: “It’s nice to
hear that you enjoy your stay here- keep up the good work!” The only thing I felt in that moment was pure relief. My PI’s
comforting smile and the giggle of the rest of the party crew who were eavesdropping gave me no other option but to laugh.
• Make sure you start preparing for your J1-visa at least 6 to 9 months prior to your departure- getting through the US
embassy procedures could be very time-consuming.
• If you don’t have a place to stay in the States, the Craigslist could be helpful: www.craigslist.org
• A colleague of mine in the lab used to say: “The best thing about Boston is that it’s close to NYC!” Travelling along
the East Coast can be easy, comfortable, and reasonable: check out www.boltbus.com
• If you have a Deutsche Bank account, you can use the Bank of America ATMs at no charge. That could be very useful
for your initial time in the US, especially when you don’t want to carry too much cash around.
Abstract on Research Topic – Mariya Mollova
Title:
Growth and proliferation in the human heart- from infancy to senescence
Authors:
Mariya Mollova, B.Kuhn, J. Savla
Institution:
Children’s Hospital Boston, Harvard Medical School, Boston, MA
Introduction:
For decades, the human heart has been considered to be a post-mitotic organ. Based on the propensity of the myocardium
towards scar formation and the extremely low incidence of cardiac tumors, it has been believed that it is terminally
differentiated and incapable of self-regeneration upon damage. The injury-related cardiomyocyte loss is irreversible and
associated with a substantial risk for the development of a life-limiting heart failure. Recent studies provide evidence that
human cardiac myocytes are capable of division after myocardial infarction and reach mitotic indices of up to 0.08% in the
border zone of the injured ventricle. New discoveries based on Carbon-14 dating have suggested that human heart muscle cells
undergo a constant renewal after birth even without injury and that younger cardiomyocytes show a higher turnover rate than
old ones.
Study population: Our research was approved by the institutional review committee of the University of Sydney and exempt
from review at Children’s Hospital Boston. Myocardial tissue samples derived from 37 human hearts procured for
transplantation, but not used, were provided by the tissue bank of the Muscle Research Unit at the University of Sydney.
Exclusion criteria were family history of inborn or acquired heart disease, cardiomyopathy, or sudden, unexplained death.
Immunofluorescence microscopy: Cryosections of the myocardial tussue samples were randomized in a systematic way and
stained with different cell cycle markers. We used primary antibodies against tropomyosin, troponin I, H3P and aurora B kinase
for detection and Alexa-fluorophore conjugated secondary antibodies for visualization. Nuclear counterstain was performed
with 4’, 6’-diamidino-phenylindole.Images were obtained using a spinning-disc confocal microscope (DSU, Olympus), and for
image acquisition, the γ- value was set at 1.
All quantifications were done by two blinded observers who were unaware of the samples’ corresponding ages.
Quantification of fibrosis: We stained 15 cryosections per heart with acid fuchsin orange-G and 15 random images were taken
on each section (Zeiss AxioPlan2). We quantified scar size from these images using Metamorph software via digital color
thresholding.
Statistical analysis: All statistical analyses were made with the GraphPad software, and the numbers are represented as means
+/- SD. The cellular and cardiomyocyte nuclear count was performed using the optical dissector method, whereby an average of
60,000–80,000 cardiomyocyte nuclei per heart sample was counted.
Results:
Myocardial fibrosis: The percentage fibrosis per heart did not show any significant difference over age (P=0, 45, r²= 0.002,
Pearson’s test). When fibrosis was quantified as percentage fibrosis of total tissue in each image, fibrosis was still not
significantly different (P = 0.058, r² = 0.01). These two measurements are significantly correlated with each other, suggesting
that they are measuring the same thing (P < 0.0001, r²=0.808).
Cardiomyocyte karyokinesis: The number of cardiomyocyte nuclei undergoing mitosis in the newborn heart (0.016142 %) is
approximately 8 times higher than in a 59-year old one ( 0.00268%).
Note that data about human cardiomyocyte cytokinesis still has to be assessed. Project is ongoing.
Conclusions:
The numbers are compatible with earlier findings based on Carbon 14 – dating of isolated cardiac muscle cells, suggesting that
human cardiomyocytes are renewed at a rate of 1% per year at the age of 25 and 0.45% at the age of 75.
Note: Mariya Mollova’s stay at the Children’s Hospital Boston was funded by the German National Academic Foundation.
Mariya Mollova with Prof. Bernhard Kuhn and other lab members at Children’s Hospital Boston
Mariya Mollova with Mr. and Mrs. Dasari
in San Francisco
KATHERINA PETER
Home Institution:
Hannover Medical School
Host Institution:
Vanderbilt Medical School,
Nashville, USA
The two-month period at Vanderbilt was the most fructuous time I had during my whole education. The teaching was not only
challenging but also friendly. It is a very rare and admirable chance for a German 4th year student to get the same tasks as an
American last year student; e.g., presenting patients, taking care of “my” patients, and making treatment suggestions. I was
fully integrated into the teams and benefited greatly from the formidable willing-to-teach faculty and non-faculty.
I was always allowed to shadow or to ask questions, which were answered in the most instructive way at all times. I never felt
as encouraged to learn as at Vanderbilt. The friendly contact with the attending physicians daily during teaching rounds, was a
completely new experience to me.
Since organization was in Ms. Owens’ hands, everything went like clockwork. A room in a fully equipped apartment was
offered to rent, visa papers were sent immediately, and someone picked me up at the airport and brought me to Ms. Owens’
office.
My fellow students were friendly and helpful to me, they often helped me with the everyday problems that I was exposed to,
and invited me to private get-togethers.
I also had the opportunity to travel around and gain an impression of the southern part of America.
Nashville is not exactly made for pedestrians, so I had difficulties in finding a grocery or going downtown. However, I was
often invited to be taken to wherever I had to go to. It is somehow difficult to maintain a more or less healthy diet, because
fruits, vegetables and other healthy things are comparatively expensive.
Most Humorous Incident: There was no specific one. Things that astonished me: a McDonald’s in the entrance hall of the
main hospital, a 24hr library with free copy service, cup cakes quite rich in content, parties from 5pm-8pm (we had so much
fun!).
Helpful Hints for Future Students: Be patient during preparation time. Your most important contact is Ms. Owens. As soon
as she takes care of you, things accelerate impressively. Vanderbilt students are more than willing to help you with any medical
or non-medical issue, just ask. Change your money before you arrive, or directly at the airport, because in town there is no
exchange office. Try to learn the English language technical terms for your chosen field; it may ease the start.
Note: Katherina Peter received no third-party funding for her time in the U.S.
DANIEL ESTEVEZ PRADO
Home Institution:
Technical University of Munich, Faculty of Chemistry
Host Institution:
Department of Therapeutic Radiology, Yale University School of Medicine,
New Haven, CT
Research Mentor:
Joanne Weidhaas, M.D., Ph.D.
Before I applied for the BMEP scholarship I didn't have any experience of the U.S., nor did I
have any stronger relationship to the country. Thus my image of the American experience
was mainly made up of stories told by friends, readings, assumptions, and the general
prejudices one might come across when living in Europe. Some proved to be true, most did
not. Now I think it is probably the most diverse, interesting and also exhilarating country I have been to, despite any difficulties
and differences with Europe.
Living in New Haven is a contrast itself; between wealthy and poor neighborhoods, Ivy League Schools and working class,
New England's beauty and depressing urban areas, kindliness and competition. It can cause sadness and joy, but is steadily
informative and inspiring. Also, living quite close to New York always gave me the opportunity to escape from my every day
life and experience a city, which is the epitome of the American Way and not typically American all at the same time. Between
Boston and New York there is a lot to discover and I really enjoyed science, culture and many other offerings.
I performed my research in the group of Joanne Weidhaas, whose lab is focused on the utilization of microRNAs as biomarkers
and therapeutics in cancer. I am especially grateful for this opportunity, since I am very interested in RNA research. I have met
a lot of nice colleagues. Not only in the field of science I did I find this country to be full friendly and supportive people.
I was planning to take this chance to broaden my horizon, improve my English language skills, and of course to take advantage
of the world-class research environment in the United States. Eventually, I did not only find a deeper understanding of the
American way of life and career opportunities, but also true friends, once-in-a-lifetime experiences, and most importantly, I
learned a lot about myself. My personal gains and professional advancements are beyond any expectations, and I would highly
recommend anyone to face the BMEP challenge and accomplish this research year abroad.
I was unlucky enough to suffer from severe disease during my time at Yale, and a few months later I had to undergo urgent oral
surgery. Thus, I had to deal a lot with the American health system, its shortcomings and German-like bureaucracy when making
a reimbursement claim. I recommend that anyone choose a good foreign travel insurance, which should have an office or a
reliable partner in the United States.
Shortly after leaving the ATM of my local bank, I realized that I wasn't carrying my laptop bag in either of my hands. After a
(record-breaking) sprint back, I couldn't find it anywhere, not even with the help of the entire security service. I left my name
and phone number with one of the kind customer consultants, well knowing that this wouldn't change anything. When I arrived
in downtown New Haven, smiling about a sudden intuition I had had seconds before, I received a very nice call from the bank
manager, who apologized and offered me his support to file the case with the police. I felt really bad and a little bit embarrassed
to tell him that I had just remembered that I never took my laptop with me...it was still in my apartment. As a biochemist, I
claim myself to be a real scientist who is sometimes allowed to live in his own world and be confused in real life.
- Read this and other BMEP yearbooks, especially the reports of students who went to the same place you are going to. I
needn’t repeat all the very good hints my scholarship fellows already put down on paper.
- Contact me: It seems like I will stay in this area until summer 2011...so do not hesitate to contact me any time if you need
help or advice for your time in the US and especially New Haven: [email protected]; [email protected]
Tel: (001) 203.554.5309
Abstract on Research Topic – Daniel E. Prado
Title:
MicroRNAs in Cancer: Regulation of DNA Damage Response.
Author:
Daniel E. Prado
Institution:
Department for Therapeutic Radiology, Yale School of Medicine, New Haven, CT
Introduction:
MicroRNAs (miRNAs) are 19–23 nucleotide RNA molecules that are transcribed from the genome and function as posttranscriptional regulators of eukaryotic gene expression by acting through the RNA interference pathway. They eventually
target partially complementary sequences in the 3' UTRs of particular messenger RNAs, which finally leads to the silencing of
the respective gene.
This mechanism constitutes a broad and crucial layer of gene regulation, since several hundred miRNAs have already been
discovered and approximately 60% of mammalian genes seem to be targeted by such regulatory elements. They widely
contribute to the regulation of cell cycle checkpoints and apoptosis, as well as differentiation, proliferation and aspects of
cellular metabolism. The role of these non-coding RNAs is emerging as critical component in controlling cell-fate and
contributor to carcinogenesis. For instance, DNA damage induced by ionizing irradiation provokes extensive changes in
miRNA expression and consequently gene regulation.
Investigating the role of miRNAs regulating mRNA translation in response to radiation will therefore shed further light on how
cells control cell-cycle arrest, genomic instability and cell death in order to deal with the occurring damage. These cellular
responses are very complex and involve many pathways, but a further understanding might substantially extend the knowledge
about the induction of carcinogenesis and implications of miRNAs as biomarkers, novel drug targets and therapeutic tools for
the treatment of human cancers.
To explore the role of miRNAs in cellular response to ionizing radiation, global alterations in the expression of miR-19a (the
miR-17-92 cluster), miR-29c (the miR-29 family) and miR-34a in irradiated cells have been examined. We monitored the
expression levels and activity of these miRNAs by utilizing qRT-PCR based TaqMan® assays (ABI), microarray data
evaluation, Dual-Luciferase® Reporter assays (Promega) and chemiluminecscent based miRNA plate assays (Signosis, Inc) in
A549 lung cancer cells treated with gamma-radiation.
Sub-cloning of miRNA target sequences and their mutants into the reporter gene containing psiCHECK2 vectors was carried
out using the corresponding NEB products and reagents, while cell transfection was achieved through Lipofectamin2000. Cell
culture dishes were exposed to 2Gy, 4Gy and 8Gy using a 137Cs irradiator (Mark I Model 68) and cells were lysed 0.5, 1, 2, 4, 8
and 16 hours after exposure. Total RNA was collected using the mirVana kit (Ambion) according to its standard protocol and
used in the mentioned experiments utilizing the Synergy™ HT Multi-Mode Microplate Reader (BioTek) and 7900HT Fast
Real-Time PCR system (ABI).
Beyond that, experiments have been designed to further investigate up- and downstream targets of the investigated miRNAs as
well as potential radiation specific aspects of miRNA biogenesis and action. These approaches involve the use of C. elegans as
a model system, RNAi, recombinant protein expression, pulldown and numerous continuative assays. A more detailed
description can be obtained upon request.
Results:
The results provide a first glimpse to indicate the involvement of miRNAs in radiation-induced cellular response and will lead
to further functional studies of the molecular details of the involved mechanisms. A full discussion of the implications of these
findings is far beyond the scope of this research abstract, but will presumably be provided in one of the upcoming publications
of the Weidhaas lab at Yale University.
Note: Daniel Estevez Prado received partial funding for his BMEP time in the U.S. from DAAD (ISAP initiative).
INES RUDOLF
Home Institution:
Department of Biochemistry, Heinrich-Heine-Universität Düsseldorf
Host Institution:
Department of Neurosurgery,
Yale University School of Medicine, New Haven, CT
Research Mentors:
Anthony van den Pol, PhD; Guido Wollmann, MD
Thanks to the BMEP, I got the amazing opportunity to spend 9 months at one of the best universities in the world. My mentors,
Professor Anthony van den Pol and Scientist Guido Wollmann, gave me a great welcome last August and made my research
experience interesting, educational and very rewarding. I got to work on my own research project and thus learned a lot about
designing, organizing and finally completing a project.
My lab is located at the Med School, which is a beautiful place. I spent many hours in the library, checking out the extremely
beautiful historical library or the very comprehensive book collection. You can get any book you can think of. I even got to take
a look at Robert Koch’s original publications from 1890.
All of this is, of course, amazing as it is. But one of the most special things about this year are how many extremely interesting
and fascinating people I have met. I remember parties with 10 guests who majored in 10 different subjects and came from 10
different countries. The kind of discussion that emerges from this set-up is just unbelievable. I have never met more openminded, tolerant, and equally interesting and interested people in my entire life.
As predicted by most of the past participants, getting the DS-2019 really is the greatest difficulty. Start the application process
as soon as possible, and call people over and over again if you don’t hear anything about the form.
Last October, my roommate and I decided to grow our own pumpkins for Halloween. She logged on to Twitter to tell her
friends about it and said: ‘Went to Target and picked up a new project. I’m growing a pumpkin!!’ She works for Yale’s Office
of Public Affairs and, unfortunately, confused her own Twitter account with Yale’s account that she also covers. We could not
stop laughing for days and she still gets made fun of at work.
• If you come to New Haven, become a member of the YaleInternational Group by sending an email to this address:
[email protected]. Whenever someone is offering housing, furniture etc., you will get an
email.
• You don’t come to the U.S. to bury yourself in the lab; you can do that in Germany without going through all the visa
issues. The educational environment of universities like Harvard and Yale is amazing. Make the most of it!
Abstract on Research Topic – Ines Rudolf
Title:
Optimizing the infection rate of the oncolytic vesicular stomatitis virus by adaptation to glioblastoma cells
Author:
Ines Rudolf
Institution:
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT
Introduction:
Glioblastoma is a malignant astrocytoma and WHO grade IV tumor. Despite a disciplinary treatment regimen, the prognosis is
dismal with most patients dying within a year of diagnosis. This is in large part due to the multifocality of the disease, an
infiltrative growth within otherwise normal brain tissue and the impermeability of the blood-brain-barrier for most therapeutic
agents. With that, novel experimental treatment avenues are pursued to overcome limitations of current treatment modalities.
One particularly promising approach is the use of viruses to infect and destroy glioblastomas. Compared to viral vectors used in
conventional gene therapy, oncolytic viruses are replication-competent viruses that specifically target tumor cells, kill them by
means of a lytic viral life cycle, and release viral progeny for a new round of tumor-targeting infection. In previous studies
vesicular stomatitis virus (VSV), a non-human pathogen, has been shown to have a strong intrinsic oncolytic potential. It has a
very low infection rate of normal healthy tissue due to its high sensitivity to antiviral actions of interferon. In contrast, many
cancer cells are found to have defects in their interferon pathway rendering them highly susceptible and defenseless for VSV
infection. Here we use a recombinant version of VSV and attempt to enhance the infection rate by evolutionary adaptation to
glioblastoma cells. Due to a high error rate of the RNA-dependant-RNA-Polymerase, changing culture environments might
propel viral mutants with higher glioblastoma affinity.
The adaptation of VSV-1’GFP to glioblastoma cells was achieved by repeated infection of cells and subsequent harvesting of
the progeny virus. The selection of potentially promising variants was made through plaque assays, selecting and propagating
the largest plaques. The basis for the selections was the assumptions that big plaques represent VSV variants that have a higher
infection rate than variants that lead to the appearance of smaller plaques. Plaque assays were conducted on confluent
monolayers of U-373 cells. After a short incubation, the virus solution was removed and the monolayer was covered with an
agarose overlay. Plaques were measured after 24h of incubation using an Olympus IX 71 fluorescence microscope.
Results:
After 48 generations of propagating the largest plaques of each generation, an increase in plaque size of up to 164% of control
plaque size was observed. Infection of healthy human brain cells with the virus variants of Generation 48 showed plaques the
size of 20-30% of control plaque size.
Conclusions:
Since the increase in size is not yet steady from generation to generation, further testing of the variants is required. This
includes sequencing of the genome and identifying potential newly acquired mutations. Together, adapting oncolytic viruses to
specific tumor environments may hold potential for enhancing their oncolytic profile.
Note: Ines Rudolf received funding for her BMEP time in the U.S. from DAAD (ISAP initiative).
INSA MARIE SCHMIDT
Home Institution:
Department of Nephrology,
Host Institution:
Department of Nephrology,
Yale School of Medicine, New Haven, CT
Research Mentor:
Lloyd Cantley, MD
Before I came to the United States within the BMEP program, I had been here just once for a short trip to NYC. To come to the
U.S. for a year or longer seemed to be an incredible chance, and now I can say it was! Getting used to many, many cultural
differences, finding new friends, overcoming linguistic barriers, or sometimes the feeling to be just by yourself in a foreign
country are experiences I never want to miss.
And, what doing research in an environment such as Yale offers to international students is amazing. Regarding my research, I
had the chance to work in Lloyd Cantley’s lab in the Department of Nephrology. It was the opposite of lots of things I have
seen before. Here I found open doors to the office whenever there was a question, open discussions whenever it was needed,
and the most important thing, open minds for every stupid idea you brought.
In summary, the time I have spent was much more than scientifically informative - I think it was simply unbelievable.
I would say the first weeks I spent in New Haven were more than hard. Missing all your very close friends, family and parents,
getting used to the American lifestyle, and having some troubles with the English language is not easy at all. But after a while
you adapt to the U.S., and Skype is the perfect thing to stay in contact with friends and family at home.
There have been so many humorous and funny incidents, that I don’t want to pick just one. Especially at the beginning, on
every single day, I felt like a little idiot. Sometimes it’s just hard to see how German you are…
Just a quick idea: Download Skype, get a cell phone and try to get a Social Security number as soon as possible. It makes life
easier! And some German recipes are really helpful…
Abstract on Research Topic – Insa Marie Schmidt
Title:
Brp-39 function in acute kidney injury
Author:
Insa Marie Schmidt
Institution:
Department of Nephrology, Yale School of Medicine, New Haven, CT
Introduction:
The goal of this project is to determine the role of Brp-39 in the kidney. Brp-39 or its human homologue YKL-40 are Chitinaselike proteins. This means that they are able to bind Chitin, which is the second most common polysaccharid in nature, but have
no chitinolytic activity. Chitin is known as a component of lower organisms like bacterial cell walls and fungi. There are tons of
it recycled at the ocean floor each year and interestingly, Cholera is able to survive during the dorment season by degrading
Chitin. Humans and mammals in general do not synthezise Chitin, but they do synthezise Chitinases and Chitinase-like
proteins, probably to deal with several kinds of pathogens. In addition to that, Brp-39 is linked to different kind of diseases
from cancer, rheumatoid arthritis or asthma. In patients with asthma increased levels have been found and this directly
correlates with the severity of the disease. It is our interest to determine the role of this protein in the kidney in the context of
repair and recovery after acute kidney injury.
We proposed a series of in vitro experiments using primary epithelial cell cultures isolated from mice and in vivo studies using
the Brp-39-/- mice and wildtype animals. To analyse the function of Brp-39 in acute kidney injury these mice undergo
ischemia/ reperfusion surgery. This procedure includes a nephrectomy on the right side and clamping of the left renal pedicle
for different timepoints. We study Blood Urea Nitrogen and creatinine to analyse the kidney function and look for pathological
changes in the renal histology.
Results/ conclusions:
Data analysis and the results of additional experiments will be performed soon.
Note: Insa Schmidt received funding for her BMEP time in the U.S. from DAAD (ISAP initiative).
CHRISTOPH SCHÜNEMANN
Home Institution:
Host Institution:
Dr. Richard A. Flavell lab, Department of Immunobiology,
& Howard Hughes Medical Institute
Research Mentor:
Chozhavendan Rathinam, PhD., Post Doctoral Fellow
Personal Reaction to the U.S. Experience:
Before my journey I expected New Haven to be like a small German student town, which turned out to be totally wrong: First,
New Haven is a very spacious town so that you cannot easily reach a shopping mall or a bigger grocery store even with a bike.
As is typical for American cities, you can only get around conveniently by car. In addition to that, there is much more (obvious)
poverty compared to any German city that I have seen. Moreover, I got several security recommendations from different people
upon my arrival: never walk to this part of the city alone; it's very important to put on the alarm system at home; don't use
public transportation because it's not safe, etc. I was very surprised to hear all that, and I did not really know what to think
about it: is it very dangerous to live here or do people dramatize and tend to exaggerate?
In contrast to that, Yale University creates kind of an air-bubble within parts of the Downtown and Eastrock areas of New
Haven. All buildings are accessible only with ID card, there are plenty of security staff everywhere, and it is possible to use the
shuttle system, including buses that run on a schedule as well as on an “on-call” basis.
I was very surprised by this special atmosphere and more so when I learned about all the diverse programs and activities that
the university and the Yale community offer. So many different nationalities encounter each other, and I soon realized that
within this community I probably felt more like a foreigner than did others who looked at me.
Living and working together with people from all over the world was new and very exciting to me. I learned a lot about
different cultures and mentalities, which was great fun and gave me new perspectives on a lot of things.
All in all New Haven/Yale is a very special kind of place, and for sure I gained a lot of amazing, interesting and important
experiences that I would not have liked to miss.
At the beginning of my stay I was confronted with a lot of new things: a new private life and working environment, a full-time
job instead of studying, a lot of theory and techniques to learn, etc. It was very challenging for me to strike a work-life-balance
within this “mess” and to find a rhythm as I was used to having in Germany.
Never order food or drinks in a “large” size without asking what to expect, because you can easily end up with 1.0 L of coffee
or similar surprises.
The DS2019 issue can potentially be a quick process, if you know how it works! Ask alumni how they got it and which offices
(or persons) you should contact. At Yale the OISS is very helpful: http://www.yale.edu/oiss/.
American life is made for cars. Consider getting one, if you have enough money.
It will especially facilitate the discovery of the surroundings of New Haven. There is beautiful nature and great possibilities for
biking or hiking.
Abstract on Research Topic – Christoph Schünemann
Title:
The role of the E3 Ubiquitin Ligase Itch in Mesenchymal Stem Cells
Authors:
Christoph Schünemann and Chozhavendan Rathinam
Institution:
Department of Immunobiology, Yale University School of Medicine & Howard Hughes Medical Institute, New Haven, CT
Introduction:
Mesenchymal Stem Cells (MSCs) are multipotent cells that can give rise to different cell types of the mesenchymal lineage,
such as osteoblasts or adipocytes (Morikawa et al., 2009). In vitro they can be differentiated into, an even, broader spectrum of
cell types (e.g. neurons or muscle cells). Moreover, it has been demonstrated that MSCs possess immunosuppressive capacities
(Uccelli et al. 2008).
Because of its regenerative and immunomodulative potential, MSCs are of great interest for a variety of clinical questions and
might potentially serve as therapeutic targets. In contrast to Hematopoietic Stem Cells, which have been extensively studied,
many aspects of MSC biology remain elusive. Hence, a thorough understanding on the molecular and genetic bases of MSCs
will significantly enhance its use in therapeutics (Karp and Leng Teo, 2009).
E3 Ubiquitin Ligases mediate protein degradation via the Ubiquitin Proteasome pathway. Recently it has been shown that E3
Ligases play a key role in the signalling network of Hematopoietic Stem Cells (Rathinam et al., 2008).
To date, the signalling events governing MSC functions are poorly understood and the E3 Ubiquitin system has never been
investigated in this cell type. Thus, the present study aims on deciphering the molecular basis of MSC differentiation and
functions.
To elucidate the role of Itch in MSCs we chose the Itch KO mouse model. Approaches based on flowcytometry and
immunohistochemistry allow us to study the localization, proliferation or apoptosis of KO MSCs in vivo and to compare these
properties with MSCs from wildtype (WT) control mice. Using transgenic mice expressing a fluorescent protein we are able to
transplant Itch WT and KO MSCs to study their homing abilities.
We isolate a bulk of different cells from the long bones of WT and KO mice and culture them in vitro following a protocol that
allows a selective expansion of MSCs. We then compare the in vitro properties - as for example differentiation into
mesodermal lineage cells - between KO and WT. Subsequently, we use these cells to investigate the molecular function of Itch
through quantitative PCR,Western Blotting, protein interaction studies and retroviral mediated over expression.
Note: Christoph Schünemann received partial funding for his BMEP time in the U.S. from DAAD (ISAP initiative).
ELENA WIDMANN
Home Institution:
German Red Cross Blood Donation Service, Frankfurt
Transplantation Immunology and Immunogenetics,
Klinikum der Johann-Wolfgang-Goethe Universität, Frankfurt am Main
Host Institution:
Molecular Oncology Research Institute, Tufts University School of Medicine
Research Mentor:
Hans Klingemann, M.D., Ph.D.
Living the dream in Boston was a mind opening experience I will never forget. Boston turned out to be a great place to meet
ambitious, intelligent and international people. From the very beginning my colleagues at MORI made me feel welcome and I
am much obliged to Dr. Klingemann for giving me the chance to work and learn at this international place with its unusual
friendly working environment in downtown Boston.
I shared a flat in Cambridge, home of Harvard, MIT and students from all over the world, and was able to experience both sides
of the river, unlike many others who never leave Cambridge and miss half of the cake.
I never had serious difficulties. Well Boston is very expensive. Finding a place to live with a certain level of cleanliness and
access to the T was not easy.
Apart from that, I started missing certain things I never thought about much before: a bath tub, healthy affordable food,
Brezeln, my cozy bed at home and washing machines that actually clean your clothes instead of shrinking them…
One thing that comes to mind is the daily lunchtime. Since there was no canteen, everyone brought lunch from home. It was
always a matter of great interest what everyone else had (“are you eating frog?!”) and many jokes where made while chatting
about current affairs (Tiger Woods), the weekends (skiing trips) and teaching each other (swear) words.
• Hit Mass Ave, especially Middlesex or Enormous Room, have drinks at Top at the Hub and Bond Bar, ice cream at
Toscanini’s and J.P Licks, pizza at Upper Crust and be prepared for the 2 a.m. closing hour.
• Travel as much as you can, start with BoltBus from South Station to NYC for 9 bucks.
• Spiegel online and Tagesschau Podcast are useful to keep you posted about what is going on outside the US.
• Enjoy every single minute. It’s probably a once-in-a-lifetime opportunity.
Abstract on Research Topic – Elena Widmann
Title:
Evaluation of the Cytotoxic Effect of Natural Killer Cells on Opportunistic Pathogens
Author:
Elena Widmann
Institution:
Molecular Oncology Research Institute, Tufts University School of Medicine
Introduction:
Natural killer cells (NK cells) are lymphocytes with the ability to kill tumor cells or infected host cells without prior
sensitization. It is not clear what mechanism the use for direct lymphocyte mediated microbial killing. Granulysin, a saposinlike protein located in cytotoxic granules is capable of killing or inhibiting the growth of microbes through an interaction with
lipid components in cell membranes that leads to osmotic lysis of microbial targets. Previous studies have shown that it is
required for direct activity against Crytococcus neoformans, an opportunistic fungal pathogen that enters the host through lungs
via inhalation of spores leading to uniformly fatal CNS infections and meningitis in immunocompromised patients. However
NK cells also express perforin, a calcium-dependent pore-forming protein, whose entry into a target cell membrane creates a
signal for the target cell to repair the damage by endocytosing the perforin and surrounding plasma membrane and helping
Granzymes to deliver proapoptotic signals. We questioned whether the human NK cell lines NK-92 and YT use granulysin, or
whether they use perforin to inhibit Cryptococcus neoformans.
C. neoformans
CAP 67 (ATCC 52817, acapsular mutant of 3501) was obtained from the American Type Culture Collection (Manassas, VA).
Cells and cell lines
YT cells were obtained from DSMZ (ACC 434 ) and cultured in medium containing IMDM, 10% FCS, and antibiotics. NK92
cells were maintained in Myelocult medium, supplemented with IL2. Primary NK cells were isolated from PBMC by the
MACS negative selection system and resuspended in medium containing RPMI, 20% FBS and Antibiotics. The purity of NKs
was greater than 90%, as determined by flow cytometry. For some experiments, NK cells were treated with 50 µM 3,4
Dichloroisocoumain (30 min), 100nM Concanamycin A (2h) or 2mM EGTA (17h).
Contact vs no-contact
To determine whether direct cell contact is required for anticryptococcal activity of NK cells, a cell culture insert with a pore
size of 0,45µm was put into the wells of 24-well culture plates. NK cells and Cryptococcus neoformans were placed in a ratio
of 100:1, and cultured for 24h. The effect on C. neoformans growth was determined, as described below.
Immunoblot analysis
Cells were lysed in RIPA lysis buffer. Protein from the lysates of 5x10^6 cells was loaded in a 10% Tris-glycine gel, separated
by electrophoresis, transferred to a PVDF membrane, and blotted with polyclonal antigranulysin (sc-16968) goat serum (1/200
dilution). The bands were visualized using HRP-conjugated anti-goat IgG (1/5000 dilution) with the ECL plus Western blotting
detection system. The membranes were then labeled with a 1/10000 diluted mouse anti-actin mAb (8H10D10), and bands were
detected, as described above. For the detection of perforin, the membranes were blotted with a mouse anti-perforin mAb
(ab47225) (1/200 dilution), and the bands were visualized, as described above.
Anticryptococcal activity of YT cells
A CFU assay was performed. C. neoformans were incubated with or without NK cells (E:T 10:1 to 100:1). The number of
CFU of C. neoformans per well was determined at 4 or 24h by lysing the NK cells with 0.1% Triton X-100, followed by 1/10
and 1/100 diluting and spreading onto Sabouraud’s dextrose agar plates. An increase in the number of C. neoformans compared
with the inoculum ndicates proliferation. Values lower than the inoculum indicate killing.
Results:
Analysis and evaluation of this study will be performed soon.
Note: Elena Widmann received partial funding for her BMEP time in the U.S. from DAAD (ISAP initiative).
ST. PETERSBURG CONNECTION
ELENA CHIRVON
Email: [email protected]
Home Institution:
Institute of Immunology Moscow
Host Institution:
Medical School Hannover
Department of Molecular Hematopoiesis
Hannover, Germany
Research Mentor:
Julia Skokowa, PhD.
Elena Chirvon received partial funding by the B.Braun Melsungen Fellowship for her stay in Germany.
Dr. Julia Skokowa (Institute of Immunology Moscow)
and Prof. Dr. Welte (Medizinische Hochschule Hannover)
Dr. Julia Skokowa (Institute of
Immunology Moscow) and students
Abstract on research Topic – Elena Chirvon
Title:
Quantification of CD34 during vitamin B3-treatment in patients with congenital neutropenia by FACS.
Author:
Elena Chirvon
Institution:
Medical School, Department of Molecular Hematopoiesis, Hannover, Germany
Introduction:
Severe congenital neutropenia (CN) is a rare bone marrow failure syndrome with a high incidence of acute leukemia
characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil
counts below 0.5x109/l. Point mutations in the gene for the granulocyte colony-stimulating factor (G-CSF) receptor CSF3-R are
highly predictive for leukemic development in CN patients. The underlying genetic defect of Kostmann syndrome has recently
been identified as mutations in the HAX1 gene (in autosomal recessive congenital neutropenia). Lymphoid enhancer-binding
factor 1 (LEF-1) is a decisive transcription factor in granulopoiesis. Loss of the transcription factor LEF-1 expression and
subsequent C/EBP and downregulation reduces survival and differentiation of granulocytic progenitors, leading to the
‘maturation arrest’ of granulopoiesis in bone marrow and decreased blood neutrophils. Nicotinic acid and nicotinamide are
members of the vitamin B family, and are precursors of NAD. Recently it was found that several nicotinic acid-related
compounds induced apoptosis in HL-60 cells and other human cancer cells. CD38 expression and accumulation of cADPR
were found to play a causal role in mediating granulocytic differentiation induced by retinoic acid.
Hematopoietic cells (HPC): CD34+, CD33+ and CD38+ cells. Cell lines (non-adherent and adherent): KG-1a, HL60, NB4,
THP-1, Jurkat, U937, K562 and 293T. Quantitation of CD34, CD33 and CD38 by FACS in healthy donors and patients with
CN. According to presence of various cell surface markers before and after transduction with particular shRNAs or
treatment with particular cytokines analyzed by FACS have been characterized of various subsets of primary HPC and cell
lines. For the identification and quantification of specific intracellular proteins involved in hematopoietic cell differentiation
(HAX-1, LEF-1 and HS-1) carried out extraction and subsequent analysis by western blot of sub cellular fractions from
cells. Also changes to the functions of neutrophils have been analyzed by FACS: degranulation (CD63, CD66b) in response
to relevant stimuli (PMA, CB, fMLP) in patients with CN compared to healthy donors.
Results:
A protocol exists for isolation and quantification by FACS of CD34+ hematopoietic cells and expression of G-CSF, GM-CSF,
M-CSF by CD34+ and CD38+ cells. Max. expression of CD34 and CD33 was observed on Jurkat and U937 cells. During
vitamin B3-treatment observed increasing expression of CD34 and with them GM-CSFR, in healthy donors more than patients
with CN. Max. expression of CD38 was observed on THP-1, less on Jurkat and more on KG-1 and HL-60 cells. After treatment
with NAMPT, an essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered granulopoiesis,
inducing neutrophilic granulocyte differentiation and FK866, revealed increasing (in case of NAMPT) and decreasing (in case
of FK866) expression of CD38 for deferent cell lines at different time-point. Also we compared expression of degranulation
markers on neutrophils from CN patients and healthy volunteers. Surface expression of CD63 (LAMP3) in non-stimulated and
phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils of CN patients were significantly higher in comparison. During
vitamin B3-treatment we also observed increasing expression of CD63 and CD66b in both groups, significantly more in CN
patients. Western blot analysis of sub cellular extracts obtained from KG-1a, HL-60, NB4, THP-1, Jurkat, U937, K562 and
293T cell showed the largest concentration of LEF-1, HAX-1 and HS-1 in Jurkat cells, also high level of HAX-1 was observed
in KG-1a cells. Less concentration of these proteins was observed in KG-1 and NB4 cells. The highest concentration of LEF-1
noted in nuclear fraction, for HAX-1 was in chromatin bound and membrane fractions. Western blot analysis of sub cellular
extracts obtained from CD34+GCSF+ cells after treatment CD34+ cell with GCSF showed the highest level of HAX-1 in
membrane extracts with max expression in 3 hours, a lower level of HAX-1 was noted in chromatin bound fraction with max at
first point (0 hours). The highest level of LEF-1 in zero point was noted in membrane fraction with furthermore high level of
this protein noted in chromatin bound fraction.
Conclusion:
Further experiments are needed to confirm these results. Revealed changes can help understand the effects of the interactions
between transcription factors (LEF-1, HAX-1, HS-1) on myeloid lineages in healthy and especially in CN patients. Further
information on the expression pattern of receptors in target cells and the dosages of cytokines and hormones that are optimum
for expression will probably be required for advances in clinical treatment of leukemia or, eventually, all types of cancers.
MIKHAIL DINIKIN & YULIA DINIKINA
E-Mail: [email protected]; [email protected]
Home Institution:
Saint Petersburg State Medical
University of acad. I.P.Pavlova
Host Institution:
Mentors:
Lowerence Grigulle, M.D.
Professor Christoph Klein, M.D.
Personal Reactions to the German Experience:
During our shared internship in Germany, Hannover, based at MHH, we received a wonderful theoretical basis and good
experience for our future practical work. We plunged into the atmosphere of the friendly work collective and improved our
knowledge of pediatric oncology and hematology. Most of the time was spent in the operating rooms. The head of department,
Professor Christoph Klеin, frequently asked our opinion about future treatment strategies for patients. He sometimes asked
difficult questions, but always gave an explanation on points we didn't know.
How easily and knowledgeably they carried out the operations was wonderful. During the operations the most modern materials
and diagnostic studies were used. In the course of the operations, the surgeons tried to comment on the most difficult stages.
While in the department of Prof. M.J. Gebel, we became acquainted with the basic criteria of diagnostics of the liver and
pancreas, the method punction biopsy and drainage of cavitary formations.
We would like to express our gratitude to Professor Hilmar Stolte and Dr. Svetlana Orlova for their support, their willingness to
help, and their kindness, as well as to the doctors at MHH for their understandable explanations and their hospitality.
The main barrier during our practice time in Germany was a low level of German.
There were so many pleasant and humorous moments, so that we hardly know what was the most comic.
The success of your future practice will depend on your purposefulness and willingness to learn something new. Be selfconfident, and do not be ashamed to ask questions or to show your true self, and this way success will be on your side.
Note: Mikhail Dinikin & Yulia Dinikina were supported by IALS/B.Braun Melsungen Fellowship.
Yulia Dinikina and Mikhail Dinikin with the Head of Department of Pediatric Oncology, Professor Christoph Klein, M.D.
ANNA KERN
E - Mail: [email protected]
Home Institution:
Host Institution:
Institute of Experimental Medicine, St Petersburg
Research Mentors:
Dr. Alexeij Sokolov
Prof . Vadim Vasilyev
Personal Reactions to the Russian Experience:
My experiences may differ a little to experiences from other countries.
The limited means of technology makes the follow-up of mistakes much easier and possible. As the methods are basically the
same, the technical standard in Germany often makes this very difficult due to the complexity of means and the lack of selfpreparing of solutions and substances in intermediates steps. However, this enforces the spirit of enterprise. In Germany I have
often felt an atmosphere of everyday routine where enterprise was missing. Every experiment should be approached with
curiosity.
Altogether, the atmosphere of the Institute - where the famous researcher Ivan Pavlov performed the salivary conditioning of
dogs - resembles how I imagined one to be 100 years ago. Today research is too often a materialistic science and not a human
science. One should always bear in mind that medical research is research of the human being. For my part I consider it helpful
to have an awareness not only of one’s speciality, but also for of the world around. It was surprising to see how much more
general education the Russian researchers have. Every student of the natural sciences has to study philosophy. In my opinion, it
is not only necessary to have the skill of deduction, but to start one’s experiment from a vision which has not risen from logical
deduction alone. The spiritual surrounding for this is therefore of vital importance.
The belief that we can master everything with our intellect means that things often do not succeed. Maybe in Russia the
fallibility of the human being is better illustrated in everyday life – which provides nutrient media for an enterprising soul.
The technical standards may not always be the ones we are used to. This makes one realize how superfluous these things can
often be. Concerning the language – communicating in Russian makes things a lot easier, of course, than in English. An attempt
to study Russian provides a lot more insights into everyday life and appreciation of the people.
The necessity of eating glucose during the procedure of preparing potassium cyanide was very fascinating - it is well known
that the last Tsar’s healer Rasputin only survived his first attempted murder because he ate rock sugar before dinner.
Get used to the fact that here you have to watch longer before you can do something yourself. Therefore you study things
deeper and people explain a lot. Studying Russian makes your integration of lab and everyday life easier.
Abstract on Research Topic – Anna Kern
Title:
MIF and its role in the nervous system
Author:
A. Kern
Institution:
Institute of Experimental Medicine, Russia
Introduction:
MIF is one of the key cytokines that regulates inflammation and degenerative processes. It has been shown that antibodies raise
against recombinant MIF have antitumor and also anti-inflammatory activity.
However, no test system to determine the native protein has been elaborated so far, and no efficient regulators of its activity
have been found. Obtaining specific antibodies against the native MIF is no less important than a search for the active protein
affecting its anti-inflammatory activity.
We are now trying to obtain rabbit and murine antibodies to human MIF.
Two proteins will be used for immunization. That is recombinant MIF from E. coli conjugated with octopus hemocyanin and
MIF purified from human and rat brain.
A special course of immunization with ovalbumin conjugated native MIF is planned. The specifity of antibodies raised against
the recombinant and native MIF will be compared.
Antibodies obtained will be used to spot MIF in the brain and spinal cord of healthy rats and of those with allergic
enzephalomyelitis. Likely, the protein will be localized in cultured cells of the neutral origin.
It is previewed to make a screening for the protein in blood and immunsystemable to regulate MIF activity.
Chromatography, Western Blotting , Immunostaining, PCR
Preliminary results:
A study of possibilities to affect the modeled inflammation and neurodegeneration by antibodies against MIF and by regulatory
proteins will be carried on.
Project ongoing!
Note: Anna Kern was supported by the IALS/B.Braun Melsungen Fellowship.
Anna Kern with Prof. Vadim Vasilyev and Dr. Svetlana Orlova
Anna Kern with Prof. Vadim Vasilyev and other lab members
FORUM II: AY 2009-2010 STUDENTS and REUNION of BMEP ALUMNI
The Farmington Inn and The Country Club of Farmington
Farmington, Connecticut
April 9 – 11, 2010
The Country Club of Farmington
Friday, April 9
9:00 – 9:30 AM
Welcome and Introduction of Morning Session Speakers –
Laurie Williams, U.S. Program Coordinator, BMEP
9:30 – 10:15 AM
“Physicians as Advocates” –
BMEP Alumnus Benjamin Schäfer, M.D. FACC, Northeast Cardiology Associates, Bangor; Maine
10:15 – 10:45 AM “Micropatterning Cell-Laden 3D Hydrogels to Induce Cellular Alignment” –
AY 2009-2010 Student Hug Aubin, Harvard-MIT, Cambridge, MA
Hug Aubin delivers his talk
10:45 – 11:15 AM Coffee Break
11:15 – 11:45 AM “A Common Variant of DISC1 is Associated with Cortical Thickness” –
AY 2009-2010 Student Stefan Brauns, Harvard Medical School, Boston, MA
Stefan Brauns delivers his talk
11:45 – 12:30 PM “Practicing Surgery in the United States” –
BMEP Alumna Claudia Hriesik, M.D., Ph.D.,
Rochester Colon & Rectal Surgeons, PC, Rochester General Hospital, Rochester, NY
12:30 – 1:30 PM
Lunch in the Tunxis Room
1:30 – 3:00 PM
Tour of the Hill-Stead Museum, Mountain Road, Farmington, CT
(includes travel time to and from the museum)
3:00 – 3:10 PM
Introduction of Afternoon Session Speakers –
Laurie Williams, U.S. Program Coordinator, BMEP
Laurie Williams introduces the speakers
3:10 – 4:00 PM
“The History of Medicine” –
Ralph Arcari, Ph.D., University of Connecticut Health Centers School of Medicine, Farmington, CT
4:00 – 4:15 PM
Coffee Break
4:15 – 4:45 PM
“Immunological Characterization of Tumor Stromal Cells Derived from Pediatric Neoplasias” –
AY 2009-2010 Student Pascal-David Johann, Children’s Hospital, Harvard Medical School, Boston, MA
4:45 – 5:15 PM
“Better Technology – What We Need: THE LIVING ATLAS”
AY 2009-2010 Student Ingolf Karst, Northwestern University;
Feinberg School of Medicine, Chicago, IL
Ingolf Karst delivers his talk
5:30 PM onwards
Free Evening
Saturday, April 10
9:00 – 9:15 AM
Welcome and Introduction of the Speakers for the Day –
BMEP Alumnus Elmar Burchardt, M.D., Ph.D.
9:15 – 9:45 AM
“Optimizing the Infection Rate of the Oncolytic Vesicular Stomatitis Virus by
Adaptation to Glioblastoma Cells” –
AY 2009 – 2010 Student Ines Rudolph, Yale University School of Medicine, New Haven, CT
Ines Rudolph delivers her talk
9:45 – 10:15 AM
“The Role of BRP-39 in Renal Epithelial Cell Death and Tissue Inflammation” –
AY 2009 – 2010 Student Insa-Marie Schmidt, Yale University School of Medicine, New Haven, CT
10:15 – 11:30 AM Coffee Break
11:30 – 12:00 PM “The Role of the E3 Ubiquitin Ligase Itch in Mesenchymal Stem Cells” –
AY 2009 – 2010 Student Christoph Schünemann, Yale University School of Medicine, New Haven, CT
12:00 – 1:00 PM
Lunch at the Country Club of Farmington
1:00 – 1:45 PM
“The Operating Room of the Future - Flight Simulator for the Operating Room” –
BMEP Alumnus Thomas Schwaab, M.D., Ph.D., Roswell Park Cancer Institute, Buffalo, NY
1:45 – 2:15 PM
“Evaluation of the Cytotoxic Effect of Natural Killer Cells on Opportunistic Pathogens” AY 2009 – 2010 Student Elena Widmann, Tufts University School of Medicine, Boston, MA
2:15 – 2:45 PM
Coffee Break
2:45 – 3:30 PM
“A Personal Journey in Personalized Medicine”–
BMEP Alumnus Elmar R. Burchardt, M.D., Ph.D., Aastrom Biosciences, Inc., Ann Arbor, MI
3:30 – 5:30 PM
Trip to Mark Twain Museum, organized by Dr. Thomas Schwaab
5:30 – 6:30 PM
Free Time
6:30 – 7:00 PM
Cocktails at the Country Club of
Farmington
7:00 – 9:00 PM
Dinner in the Main Dining Room at the
Country Club of Farmington
Relaxing over a drink
Sunday, April 11
8:00 to 9:00 AM
Breakfast at the Farmington Inn
9:30 – 10:30 AM
Students Meet with Some of the Doctors in the Lobby of the Inn
10:30 – 11:00 AM Check Out of the Farmington Inn
Laurie Williams with some of this year’s participants
IALS/BMEP FORUM II 2010 PARTICIPANTS
April 9-10, 2010
Held at the Farmington Inn & the Country Club of Farmington
Farmington, Connecticut
Speakers and Invited Guests
Ralph Arcari, Ph.D.
Assistant Professor, Department of Community Medicine
University of Connecticut Health Center School of Medicine
Farmington, CT 06032
Elmar Burchardt, M.D., Ph.D.
BMEP Alumnus AY 1989-1990
Aastrom BEliosciences, Inc.
P.O. Box 376
Ann Arbor, MI 48106
Dirk Hentschel, M.D.
Brigham and Women’s Hospital, Renal Division
Harvard Institutes of Medicine, Room 550
4 Blackfan Circle
Boston, MA 002115
Claudia Hriesik, M.D., Ph.D.
BMEP Alumna AY 1995-1996
Rochester Colon & Rectal Surgeons, PC
Rochester General Hospital
Rochester, NY 14607
Alexander Panda, M.D., M.P.H.
Clinical Fellow, Yale Univ. Medical School
Internal Medicine, Pulmonary Department
P.O. Box 208057
New Haven, CT 06520-8057
Thomas Schwaab, M.D., Ph.D.
Department of Uro-Oncology
Roswell Park Cancer Institute
Elm & Carlton Streets
Buffalo, NY 14263
Benjamin Schäfer , M.D., FACC
Medical Director, Cardiovascular Services at
Saint Joseph Hospital and Member of
Northeast Cardiology Associates
Bangor, ME 04401
BMEP USA Staff
Laurie B. Williams, B.S.
U.S. Program Coordinator for BMEP
56 Hancock Street
Ellsworth, Maine 04605
Raymond L. Williams, B.A., J.D.
Attorney and Clerk of BMEP USA, Inc. (unpaid)
Senior Partner in Law Firm of
Roy, Beardsley, Williams and Granger, LLC
P.O. Box 723
Ellsworth, ME 04605
Laurie & Raymond Wlliams
Students in BMEP Program AY 2009-2010
Transatlantic Bridge
Hug Aubin
From Ruprecht-Karls-Universität, Heidelberg
To Harvard-MIT Division of Health Sciences and Technology and
Harvard Medical School, Boston
Stefan Brauns
From Charité Universitätsmedizin, Berlin
To Harvard Medical School and Massachusetts General Hospital,
Dept. of Psychiatry, Boston
Torben Brod
From Medizinische Hochschule, Hannover
To Emory University School of Medicine, Atlanta
Sebastian Darr
To Harvard Medical School, Brigham and Women’s Hospital, Boston
Pascal-David Johann
From Eberhard-Karls-Universität, Tübingen
To Harvard Medical School, Children’s Hospital, Boston
Ingolf Karst
From Charité Universitätsmedizin, Berlin
To Northwestern University Feinberg School of Medicine, Chicago
Christian Matiaske
To Harvard Medical School, Brigham and Women’s Hospital, Renal Division, Boston
Mariya Mollova
To Harvard Medical School, Children’s Hospital, Boston
Daniel Estévez Prado
From Technische Universität, München
To Yale University School of Medicine, Department of Therapeutic Radiology,
New Haven
Ines Rudolf
From Heinrich-Heine-Universität, Düsseldorf
To Yale University School of Medicine, Department of Neurosurgery, New Haven
Insa-Marie Schmidt
To Yale University School of Medicine, Department of Internal Medicine-Nephrology,
New Haven
Christoph Schünemann
To Yale University School of Medicine, Section of Immunobiology, New Haven
Elena Widmann
From J.W. Goethe Universität, Frankfurt
To Tufts University School of Medicine, Molecular Oncology Research Institute, Boston
St. Petersburg Connection
Elena Chirvon
From NRC Institute of Immunology, Moscow
To Medizinische Hochschule, Hannover
Mikhail Dinikin
From St. Petersburg State Medical Univ. of Acad. I.P. Pavlov, St. Petersburg
Yulia Dinikina
From St. Petersburg State Medical Pediatric Academy, St. Petersburg
Anna Kern
To Russian Academy of Medical Sciences, St. Petersburg
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
Dr. Karsten Dreinhöfer, Ulm
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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•
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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
Donors – up to 100 Euros
•
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•
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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
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
Hannover
Carl-Neuberg-Str. 1
D-30625 Hannover
T +49 511 532 6662
F +49 511 532 6663
[email protected]
•
•
•
•
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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]
Medizinische Hochschule Hannover, Germany
University of Illinois, Urbana-Champaign, USA
Deutsches Herzzentrum Berlin, Germany
Freie Universitaet Berlin, Germany
University of Massachusetts, Boston, USA
Charité Universitätsmedizin, Berlin, Germany
Herz- und Diabeteszentrum Bad Oeynhausen, Universitätsklinik der Ruhr-Universität Bochum, Germany
in public / private partnership:
GBM – Association for Innovation and Technology Transfer in Biomedicine, Ltd, Potsdam – Bad Oeynhausen
[email protected]

BMEP Yearbook AY 2009/2010 (PDF 1.7Mb)

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