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PRESIDENT’S ADDRESS<br />

The Life Sciences represent a cutting-edge interdisciplinary and multidisciplinary field, building a bridge between the natural<br />

sciences and the humanities. This bridge is important regarding many aspects of Life Sciences research and education,<br />

including innovations in food technology, new medical technology and treatment options, as well as biotechnology and gene<br />

technology. These dimensions will change our personal and social lives fundamentally. We believe that the methods and results<br />

of the Life Sciences deserve our special attention at this stage of global development.<br />

It is the mission of the IALS (<strong>International</strong> <strong>Academy</strong> of Life Sciences) to foster a new generation of clinical scientists making<br />

the most of this fascinating development. Here the IALS University Network with IALS core universities can be seen as an<br />

interdisciplinary “think tank”. It is a forum addressing brand new issues in the Life Sciences, as well as a place for the<br />

production and analysis of ideas which can then be diffused by public understanding.<br />

The IALS is an international network. Each member represents a further network (of universities, institutions, organizations),<br />

making the IALS an international network of networks.<br />

Since the <strong>BMEP</strong>-Biomedical Sciences Exchange Program and IALS-<strong>International</strong> <strong>Academy</strong> of Life Sciences were founded in<br />

1979, over 1,600 German and American students, post-graduates, faculty members and scientific assistants have been placed at<br />

universities and scientific institutes on both sides of the ocean.<br />

Building on this very successful history spanning almost 30 years, we are still focusing on the areas of education and<br />

initiatives/projects involving emerging critical issues, motivating young advanced students to start careers as “clinical<br />

scientists”, while also being a forum for “Critical Issues in the Life Sciences”. This all happens on a well established<br />

transatlantic “two-way” bridge. However, we are also pleased to be opening up new horizons in the global arena, such as the<br />

Baltic Region and St. Petersburg, Guangzhou in China and Istanbul in Turkey.<br />

All of this is made possible by the support of long-standing members of the IALS Board and IALS-Development Committee<br />

(see http://www.lifesciences.net/aboutus/board.html). This Academic <strong>Yearbook</strong> is dedicated to those members who work so<br />

hard for the sustainability of IALS.<br />

Prof. Hilmar Stolte, M.D.<br />

President IALS & <strong>BMEP</strong><br />

University Professor em., Medizinische Hochschule Hannover<br />

Distinguished Professor, Charité Universitätsmedizin, Berlin


Participants<br />

Participant Home University Host University<br />

Atasoy, Cana Selen Technische Universität München The University of New South Wales, Sydney<br />

Atmanli, Ayhan Ruprecht-Karls-Universitaet, Heidelberg Harvard Medical School, Boston, MA<br />

Behnert, Astrid Medizinische Hochschule Hannover University of Calgary, Calgary, Alberta<br />

Buttgereit, Anne Universität Ulm University of California, San Diego, CA<br />

Czogalla, Jan Westf. Wilhelms-Univ., Münster University of California, San Diego, CA<br />

Deutsch, Konstantin Medizinische Hochschule Hannover The Jackson Laboratory, Bar Harbour, ME<br />

Goelzenleuchter, Meike Charite Universitätsmedizin, Berlin Mayo Clinic, Rochester, MN<br />

Greve, Tobias Technische Universität München University of California, San Francisco, CA<br />

Heinbokel, Tim Charite Universitätsmedizin, Berlin Harvard Medical School, Boston, MA<br />

Hilger, Alina Rhein. Friedrich.-Wilh. Univ., Bonn University of Michigan, Ann Arbor, MI<br />

Hoepting,Matthias Medizinische Hochschule Hannover University of Michigan, Ann Arbor, MI<br />

Hupe, Marie-Christine Medizinische Hochschule Hannover University of Miami, Miami, FL<br />

Jeng-Singh, Christian Medizinische Hochschule Hannover Mayo Clinic, Rochester, MN<br />

Kasper, Judith RWTH, Aachen Maastricht University, Maastricht, NL<br />

Kern, Anna** Medizinische Hochschule Hannover Institute of Experimental Medicine, RAMS,<br />

St. Petersburg<br />

Klukas, Jana Medizinische Hochschule Hannover Mayo Clinic, Rochester, MN<br />

Reichermeier,Kurt Justus Liebig Universität, Giessen California Institute of Technology, Pasadena,<br />

CA<br />

Rümmler, Robert Joh. Gutemberg Universität, Mainz University of Michigan, Ann Arbor, MI<br />

Schmidt-Lauber, Christian Westf. Wilhelms-Univ., Münster University of Massachusetts, Worcester, MA<br />

Schröder, Linda RWTH, Aachen Maastricht University, Maastricht, NL<br />

Sieben, Anna RWTH, Aachen University of California, Los Angeles, CA<br />

Liskovykh, Mikhail* RAMS, St. Petersburg Max Delbrück Center, Berlin<br />

* postgraduate<br />

** Anna Kern was in St. Petersburg for a second year, again funded by B. Braun – Melsungen AG. Please see the <strong>BMEP</strong><br />

Academic <strong>Yearbook</strong> 2010/11 for her personal pages.


4:00PM – 6:00PM<br />

6:00PM – 7:30PM<br />

7:30AM – 9:00AM Breakfast at the Hotel<br />

IALS/<strong>BMEP</strong> STUDENTS’ CONFERENCE<br />

April 26-28, <strong>2012</strong><br />

University of Massachusetts Boston<br />

AGENDA<br />

Day One - Thursday, April 26<br />

Check into Hotel in Boston (Double Tree Hilton Bayside)<br />

Informal Cocktail Gathering in Hotel for All Attendees<br />

Day Two – Friday, April 27<br />

9:00AM – 9:30AM Move to University of Massachusetts, Healey Library Section B<br />

9:30AM – 9:40 AM “Welcome” by University of Massachusetts Hosts<br />

9:40 AM – 10:00 AM “Greetings and Introductions of Guest Speakers, <strong>BMEP</strong> Alumni<br />

other Guests, and <strong>BMEP</strong> Students” by Prof. Hilmar Stolte, M.D.<br />

10:00 AM – 11:00AM Round Table Discussion<br />

“Biobehavioral Risk Factors” led by Prof. Siegfried Geyer, Prof. Laura Hayman<br />

and Prof. Christiane Kugler, with US <strong>BMEP</strong> Alumni and Others<br />

11:00AM – 11:15AM Coffee Break<br />

11:15AM – 4:30PM Student Presentations of Their Laboratory Research Projects<br />

Moderator: Prof. Eunsook Hyun, Associate Provost, UMass, Boston<br />

11:15AM – 11:30AM Ayhan Atmanli, Universität Heidelberg and Harvard Medical School, Boston,<br />

MA, “Generation of Aligned Cardiomyocyte Sheets from Mouse Committed<br />

Ventricular Progenitors”<br />

11:30 AM – 11:45AM Astrid Behnert, Medizinische Hochschule Hannover and University of Calgary,<br />

Calgary, Alberta, CN, “The Role of M-type Phospholipase A2 Receptor as an<br />

Autoantigen in Membranous Nephropathy”<br />

11:45AM – 12:00<br />

Noon<br />

Anne Buttgereit, Universität Ulm and Univ. of Calif. at San Diego, San Diego,<br />

CA, “The Role of PPAR delta on Neural Function and Neurodegeneration”


12:00 PM – 12:15 PM Konstantin Deutsch, Medizinische Hochschule Hannover and The Jackson<br />

Laboratory and MDI Biological Laboratory, Bar Harbor, ME, “The Role of<br />

Kynurenine 3-monooxygenase (KMO) in the Glomerular Filtration Barrier<br />

Function”<br />

12:15 PM – 1:30 PM Lunch<br />

Moderator: Prof. Stefan G.Tullius, Harvard Medical School, Boston<br />

1:30 PM – 1:45 PM Meike Gölzenleuchter,Charité – Universitätsmedizin Berlin and Mayo Clinic,<br />

Rochester, MN, “DNA Methylation and Pain”<br />

1:45 PM – 2:00 PM Tobias Greve, Technische Universtät München and Univ. of Calif. at San<br />

Francisco, San Francisco, CA, “Understanding Micro RNAs and Their Targets<br />

During Reprogramming”<br />

2:00 PM – 2:15 PM Timm Heinbokel, Charité - Universitätsmedizin Berlin and Brigham & Women’s<br />

Hospital, Boston, MA, “ Age-dependent Dendritic Cell Phenotype and Function”<br />

2:15 PM – 2:30 PM Alina Hilger, Universität Bonn and Howard Hughes Medical Institute, Ann<br />

Arbor, MI, “Gene Identification in VACTERL Association”<br />

2:30 PM – 2:45 PM Matthias Höpting, Medizinische Hochschule Hannover and Univ. of Michigan,<br />

Ann Arbor, MI, “Pathophysiology in Gastrointestinal Graft Versus Host Disease”<br />

2:45 PM – 3:00 PM Coffee Break<br />

Moderator: Dr. Elmar R. Burchardt, Vicepresident Pfizer, Cambridge<br />

3:00 PM – 3:15 PM Marie Hupe, Medizinische Hochschule Hannover and Univ. of Miami Miller<br />

School of Medicine, Miami, FL, “Tumor Markers in Targeted Therapy”<br />

3:15 PM – 3:30 PM Christian Jeng-Singh, Medizinische Hochschule Hannover and Mayo Clinic,<br />

Rochester, MN, “Gene Therapy for Chronic Pain”<br />

3:30 PM – 3:45 PM<br />

5:00 PM – 6:00 PM Cocktail Hour<br />

Kurt Reichermeier, Universität Giessen and Calif. Institute of Technology,<br />

Pasadena, CA, “Implications of the P97/VCP Adapter Protein UBXD7 in HIF-<br />

1alpha Turnover”<br />

Faculty Club of the University of Massachusetts<br />

6:00PM – 9:00PM Dinner at the Faculty Club of the University of Massachusetts at Boston<br />

Day Three - Saturday, April 28<br />

9:30 AM – 10:30 AM Brunch in the OITA conference room 2215, UMass Boston Campus Center<br />

10:30 AM – 12 Noon Round Table Discussion – Questions and Suggestions Brought up by <strong>AY</strong> <strong>2011</strong>-<br />

<strong>2012</strong> <strong>BMEP</strong> Students, US Alumni, Visitors, and Guests


SELEN ATASOY<br />

Email: selenatasoy@gmail.com<br />

Home Institution: Technische Universität München<br />

Host Institution: University of New South Wales<br />

Research Mentor: Joel Pearson, PhD,<br />

Principal Investigator and Head of the Pearson Lab,<br />

Senior Lecturer and CJ Martin Fellow at University of New South Wales.<br />

Personal Reaction to the Australian Experience: After 29 hours flight, when I finally arrived in Sydney, I was impressed by<br />

the natural beauty of the city, with its bright sunshine and amazing ocean. Diving into the ocean right on my arrival helped me<br />

to completely forget about my long flight and took away all my tiredness. Soon I started getting used to the vibrant, friendly<br />

and relaxed lifestyle of Sydney. I was very impressed by the ease and efficiency of the Australian lifestyle, which was<br />

accompanied by my warm welcome at the lab in UNSW. Exploring the research in cognitive neuroscience department, which<br />

was very new and exciting to me, in the beautiful environment of Sydney, has been a unique experience.<br />

Greatest Difficulties Encountered: Driving on the left side of the road.<br />

Most Humorous Incident: In my last week in Australia, I was travelling on the east coast and joined a three-day tour on Fraser<br />

Island. As a group we had 4 identical four-wheel drives and I somehow ended up being the driver of one of the cars. Driving on<br />

the left side of the road and changing gears with my left hand was very strange. After quite a bumpy ride on the sand and<br />

couple of near accidents, I finally started to get used to driving on the left. But when we went to get fuel before returning the<br />

cars, we realized that all the cars needed exactly the same amount of fuel except for the one I was driving… (of course it<br />

needed a lot more than the other three).<br />

Helpful Hints for Future Students:<br />

- Open a bank account with Deutsche Bank and activate it for Australia, then you can get cash out without paying any fees from<br />

any Westpac branch.<br />

- Don’t think that the weather in Australia is constantly sunny, so pack a rain coat, especially if you will be there for the<br />

southern hemisphere autumn or winter.<br />

- Plan some time for travelling, Australia is amazingly beautiful!<br />

Students’ conference Faculty members <strong>2012</strong>


Abstract on Research Topic – Selen Atasoy<br />

Title: Measuring the Metacognition of Visual Imagery using Binocular Rivalry<br />

Author(s): Selen Atasoy 1,2 , Amanda Krulis 1 , Joel Pearson 1<br />

Institution:<br />

1 Pearson Lab, Department of Cognitive Neuroscience, University of New South Wales, Sydney, NSW, Australia<br />

2 Chair for Computer Aided Medical Procedures, Faculty of Informatics, Technische Universität München,<br />

Introduction:<br />

When two conflicting visual patterns are presented simultaneously to each eye, they lead to competitive interactions in the<br />

visual cortex such that the subject consciously perceives only one stimulus at a time. This phenomenon, known as binocular<br />

rivalry, has been used to demonstrate the functional impact of visual imagery (in the absence of the appropriate external<br />

stimuli) on subsequent perception. It has been shown that visual imagery has location and orientation-specific effects on the<br />

perception of subsequent rivalry stimulus in favor of the imagined pattern. The aim of this study is to evaluate the accuracy of<br />

subjects’ metacognitive knowledge of their imagery performance in relation to the subsequent perception of a binocular rivalry<br />

stimulus.<br />

Materials and Methods:<br />

Previous to the experiment, subjects performed offline training for moving a joystick according to the intensity of a stimulus<br />

displayed on the screen. To investigate the effects of imagery and the accuracy of subjects’ metacognitive knowledge, subjects<br />

were instructed to imagine one of the two rivalry patterns previously seen in the training phase while simultaneously moving a<br />

joystick according to the vividness of the imagined pattern. After each single imagery episode, the rivalry pattern was displayed<br />

briefly, which consisted of a green vertical grating shown to the left eye and a red horizontal grating shown to the right eye. The<br />

subjects reported which of the two patterns appeared dominant after each presentation.<br />

Results/ Conclusions:<br />

The joystick movement from each trial is used as a novel method to measure self-reported imagery vividness; i.e.<br />

metacognition, and is analyzed with respect to its effect on the subsequent perception. Preliminary results suggest the<br />

correlation between the vividness of the imagined pattern (subject’s metacognition) and its effect on the subsequent perception<br />

of the binocular rivalry stimulus.<br />

Note: Selen Atasoy received funding for her <strong>BMEP</strong> time in Australia from DAAD and UNSW.<br />

Professors Stolte, Langley (Provost, UMass Boston) and Price (Prof. em., King’s College London), Students’ conference


<strong>AY</strong>HAN ATMANLI<br />

Email: ayhan.atmanli@gmail.com<br />

Home Institution: Faculty of Medicine, Heidelberg University, Heidelberg, Germany<br />

Host Institution: Cardiovascular Research Center, Massachusetts General Hospital,<br />

Harvard Medical School, Boston, MA<br />

Research Mentor: Ibrahim Domian, M.D., Ph.D., Staff Cardiologist & Principal<br />

Investigator<br />

Personal Reaction to the U.S. Experience: This is my first trip to the USA, however not my first contact with research.<br />

Boston is the area to be if you seek an opportunity to expand both your research experience and skills, with all the brainpower<br />

and creativity shared by people from all kinds of different backgrounds. I am fortunate to be supervised by my mentor, who has<br />

given me the opportunity to find my own way by allowing me to figure out many research problems on my own. Of course,<br />

Boston offers way more than its most powerful academies – it is a city you definitely feel comfortable in from the very<br />

beginning. If you don’t have a good time in Boston, you won’t have it anywhere else. Wherever I have met people, they have<br />

all been very nice and obliging, even if you needed more than just short assistance. All of this has contributed to the fact that I<br />

have had a terrific time in Boston so far, which I am looking forward to continuing.<br />

Greatest Difficulties Encountered: The visa. You can minimize trouble if you try to arrange for everything you need<br />

personally. Don’t expect anyone to do anything for you. It’s your trip and your responsibility.<br />

Most Humorous Incident: A guy who made every effort to show us the way to the riverside, even though we were willing to<br />

try out our own way and see if we ended up there. He did not let up and asked several other pedestrians for the way to the<br />

riverside. Finally, we found it – the way he had found out for us.<br />

Helpful Hints for Future Students:<br />

• craigslist.com (for literally everything you need)<br />

• Americans don’t like distance – you can get to know tons of people if you are open-minded<br />

• Go for a trip to New York City


Abstract on Research Topic – Ayhan Atmanli<br />

Title: Generation of Aligned 3-Dimensional Myocardial Tissue<br />

Authors: Ayhan Atmanli, Nikhil Vinod Mittal, Ibrahim Domian<br />

Institution: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA<br />

Introduction: Despite many advances in tissue engineering, recapitulation of native tissue structure remains a key challenge in<br />

this field. Usually, artificial scaffolds are used to mimic native tissue architecture, but ideally, engineered tissues would be<br />

made entirely of biological components. Cell sheet engineering techniques address this challenge as they rely on cells to<br />

produce their own extracellular matrix (ECM). However, incorporation of structure into cell sheets has been limited. The<br />

thermoresponsive polymer poly(N-isopropylacrylamide) (PIPAAm) is an attractive biomaterial substrate for cell sheet<br />

engineering, since it allows confluent cell layers and their associated ECM to be non-invasively removed from PIPAAmgrafted<br />

surfaces as intact sheets, simply by lowering the temperature. However, cell sheets are typically grown on uniform<br />

PIPAAm surfaces, which results in randomly oriented cells. Microcontact printing is a simple and inexpensive technique to<br />

precisely control cell shape, organization, and function, all of which are crucial for the generation of aligned myocardial tissue.<br />

Herein, we propose to combine both techniques to generate and stack aligned cardiomyocyte sheets into three dimensional<br />

functional myocardial tissue.<br />

Accordingly, the major goals for our study are the following:<br />

(1) To create grafted PIPAAm-layer on polydimethylsiloxane (PDMS) for the generation of cell sheets, and<br />

(2) To generate a micropatterned protein surface on PDMS substrates by microcontact printing for the generation of aligned<br />

myocardial tissue, and<br />

(3) To combine both techniques to generate aligned 3-dimensional myocardial tissue.<br />

Materials and Methods: A monomer solution of N-isopropylacrylamide was deposited onto PDMS-coated glass cover slips<br />

and UV irradiated to polymerize and graft N-isopropylacrylamide onto the PDMS surfaces. The presence of grafted PIPAAm<br />

was assessed with Fourier Transform Infrared Spectroscopy (FTIR). Patterned PDMS stamps with 20 µm wide, 2 µm tall<br />

ridges, separated by 20 µm spacing were used to print fibronectin onto PDMS surfaces. Immunofluorescence microscopy was<br />

used to stain fibronectin micropatterns. Microcontact printed PDMS substrates were seeded with mouse committed ventricular<br />

progenitors.<br />

Results/ Conclusions: FTIR analysis verified the presence of grafted PIPAAm. Immunofluorescence revealed that the<br />

microcontact printing on PDMS substrates was successful and seeded cells were able to grow anisotropically on the<br />

micropatterns. More experiments regarding the combination of PIPAAm and micropatterns will be performed to achieve the<br />

main goal of generating aligned 3-dimensional myocardial tissue.<br />

Note: Ayhan Atmanli received funding for his <strong>BMEP</strong> time in the U.S. from DAAD (ISAP Initiative.)


ASTRID BEHNERT<br />

Email: astrid.behnert@googlemail.com<br />

Home Institution: Hannover Medical School, Hannover, Germany<br />

Host Institution: University of Calgary, Calgary, Alberta, Canada<br />

Researcher Mentors: Mario Schiffer, M.D., Hannover Medical School;<br />

Marvin J. Fritzler, M.D., Ph.D., University of Calgary<br />

Personal Reactions to the Canadian Experience:<br />

During my stay I met many wonderful people from all over the world, and because Canada is such a multicultural country, I felt<br />

welcome right away. In general, working in the lab wasn’t too different from what I had experienced in Germany. The team I<br />

worked with was great! We often went to different places for lunch and met after work for a beer (or two...) or to go bowling.<br />

I really loved the fact that Calgary is so close to the Rocky Mountains. During the winter, I tried to go snowboarding every<br />

weekend. Unlike in Europe, boarding through the woods is allowed, and since they don’t groom the runs, you could really<br />

enjoy a powder day. I also got quite addicted to Tim Horton’s French Vanilla coffee and their awesome whole grain raspberry<br />

muffins. If my research career is not going anywhere, I will go on a tour across Canada where I’ll stop at every single Tim<br />

Horton’s and have a chat with the locals. Sounds like a good plan, right?<br />

Greatest Difficulties Encountered:<br />

The Calgary transit system is really confusing. You have to know where to get off because there is no screen in the bus telling<br />

you where you are or what station you’ll reach next. Getting to the hospital took me an hour, and I had to change buses twice.<br />

On my first day, I got completely lost on my way back home because I got off at a wrong bus station. Nothing in that area<br />

looked familiar so I had to walk up to a strange guy and ask for directions. He eventually gave me a ride, because it would have<br />

been a really long walk back home. I was thinking of my mom’s, “Don’t get into a car with strangers!” but oh well...<br />

Most Humorous Incident:<br />

Umm, it is hard to pick one incident since there have been so many funny moments and lots of them were based on inside<br />

jokes. Well, I remember one time when a colleague and I went to a restaurant and we were talking about the attractiveness of<br />

the waitresses at that place. During that conversation I accidently mixed up the words “server” and “servant” (which is more<br />

like “slave”) when my colleague suddenly started laughing. Calling the waitress a “servant” to her face would have been really<br />

embarrassing!<br />

Helpful Hints for Future Students:<br />

In the winter time, multiple cheap ski coaches run from Calgary to Lake Louise or Sunshine every weekend. Just visit the<br />

website of the ski resort where you want to go. If you’re into hockey, go to see a game with the Calgary Flames! During the<br />

summer, you have to check out the Calgary Stampede, the world’s biggest rodeo show. Don’t worry - it’s more about the rides<br />

and the shows than about torturing animals.<br />

Astrid with her colleagues


Abstract on Research Topic - Astrid Behnert<br />

Title: PLA2R as autoantigen in idiopathic membranous glomerulonephritis<br />

Author: Astrid Behnert<br />

Institution: Department of Medicine, University of Calgary, Calgary, Alberta, Canada<br />

Introduction:<br />

Membranous glomerulonephritis (MG) is a rather rare disease but one of the most common causes for idiopathic nephrotic<br />

syndrome in adults. Two different forms of MG are defined: a primary, idiopathic form, which is found in 80% of MG patients,<br />

and a secondary type caused by a number of different processes such as hepatitis, syphilis or chronic infections. In 2009, Beck<br />

et al. identified the M-type phospholipase A2 receptor as autoantigen in primary MG by immunoblot analysis and mass<br />

spectometry. Antibodies directed to PLA2R are present in greater than 75% of individuals with idiopathic MG but cannot be<br />

found in those with the secondary form of MG. PLA2R can therefore be seen as an immunologic marker for IMN which, for<br />

this reason, can no longer be called "idiopathic".<br />

Little is known about this new antigen. Therefore, we wanted to investigate antibody-antigen-interaction and to develop a more<br />

sensitive and specific assay for anti-PLA2R antibodies. A specific epitope would simplify testing for anti-PLA2R and would<br />

also open up new treatment opportunities.<br />

Materials and Methods:<br />

In order to establish a more sensitive and specific assay than the one already existing, we cloned our PLA2R constructed into a<br />

GFP vector which was then transfected into HEK cells. We developed two different indirect ELISAs. One was based directly<br />

on transfected HEK cells, the other one was on cell lysates. Diluted patient serum was used as a primary antibody. Goat anti-<br />

PLA2R was used as a standard. Diluted patient serum was defined as positive, if the absorbance of the sample was higher than<br />

the absorbance of a diluted healthy control plus two standard deviations. If it was lower, it was defined as negative.<br />

Trying to determine other markers for disease activity, we tested sera for about 80 different cytokines.<br />

For identifying antigen determinants, epitope mapping using SPOT technology was performed. Peptides covering the full<br />

length protein were spotted on a nitrocellulose membrane and potential epitopes detected by running a Western on the<br />

membrane. Potential epitopes were verified using peptide ELISA and Luminex.<br />

Results and Conclusions:<br />

ELISA: Initially, an indirect ELISA directly on PLA2R transfected HEK cells was performed, but since these weakly adherent<br />

cells got disconnected during washing, even when the plate was coated with poly-l lysine, the design of the assay was modified.<br />

Thus, no conclusion about autoantibody levels in patient serum could be made. Therefore, an indirect ELISA where plates were<br />

coated with PLA2R HEK cell lysates was established. The obtained standard curve was very precise and it was possible to<br />

calculate exact autoantibody concentrations. However, absorbances of patient samples and control samples were close together,<br />

so that sensitivity was lower than in the Euroimmune assay. Coating with only an autoantibody-specific part of PLA2R as<br />

antigen could improve testing.<br />

Western on peptide membrane: First, HRP conjugated IgG (all subclasses) was used as a secondary antibody but a high<br />

background signal and no specific dots could be observed. Since it is reported that autoantibodies in IMN predominantly<br />

belong to the IgG subclass 4, HRP conjugated IgG4 was consequently used as a secondary antibody. Fewer background and<br />

strong dots were detected. In order to verify the potential epitopes that were detected by epitope mapping, synthetic peptides<br />

(EZBiolab) were tested in ELISA.<br />

Note: Astrid Behnert received funding for her <strong>BMEP</strong> time in Canada from <strong>BMEP</strong>/DAAD.


ANNE BUTTGEREIT<br />

Email: buttgereitanne@gmail.com<br />

Home Institution: University Ulm, Germany<br />

Host Institution: University of California San Diego, San Diego, CA<br />

Research Mentor: Albert R. La Spada, M.D., Ph.D.<br />

Personal Reaction to the U.S. Experience:<br />

I am very grateful for having the opportunity to do part of my studies abroad. It is not<br />

only interesting and beneficial in terms of gaining research experience, but also<br />

incredibly valuable for personal development.<br />

I flew into San Diego <strong>International</strong> Airport by night and all I could see for at least the last 10 mins of my flight were lights.<br />

Houses, streets and population spread out everywhere. That was the first time I really recognized what I had got into by<br />

deciding to move to the US all by myself.<br />

After this first moment of realization it turned out to be not as scary as it seemed at all. My landlady made it very easy for me to<br />

feel welcome right away, and I met a whole bunch of great people I can call friends now. The lab I joined just shifted locations<br />

to the most gorgeous place one could imagine, right on top of a cliff with an ocean view from the working benches.<br />

And the city of San Diego itself? Well it’s big, but it’s also divided into many diverse neighborhoods, so it’s not too hard to<br />

settle in. The way of life down here in southern California is very laid-back. The weather is amazingly warm and sunny which<br />

is why people get spoiled to a point where they call 18°C in mid January “cold”. And the area has just so much to offer that it’s<br />

almost hard to stay inside the lab and focus on work.<br />

Greatest Difficulties Encountered:<br />

Finding an affordable place to stay while still in Germany was very hard, and I was really glad when I finally found a room 2-3<br />

weeks before starting my journey. Getting around in the US, especially on the west coast in southern California, without a car is<br />

nearly impossible. I did that for about one month and then rented a little old car.<br />

Most Humorous Incident:<br />

A running joke was the car I rented in San Diego. Jan, a fellow <strong>BMEP</strong> student, had told me about this “dirt cheap car rental”<br />

company out here. The name really speaks for itself. I got to rent a tiny Suzuki Swift with more than 170000 miles and who<br />

knows how many years that badly needed a new paint job. It could perfectly hide between all other cars in parking lots and by<br />

American standards it was obviously more like a matchbox car.<br />

Helpful Hints for Future Students:<br />

- start planning ahead regarding visa application and accommodation<br />

- join “couchsurfing” and find meetings/ social activities of the local group<br />

- most important: enjoy your time as much as possible


Abstract on Research Topic – Anne Buttgereit<br />

Title: Role of PPARδ in neuronal function and neurodegeneration<br />

Author: Anne Buttgereit<br />

Institution: Departments of Pediatrics, Cellular & Molecular Medicine, and Neurosciences, and the Institute for Genomic<br />

Medicine, University of California, San Diego, CA<br />

Introduction:<br />

Huntington’s disease (HD) is a neurodegenerative disorder displaying motor and cognitive symptoms in an autosomal dominant<br />

pattern of inheritance. The disease-causing protein huntingtin (htt) is characterized by a CAG repeat expansion in exon 1, and is<br />

thus one of nine inherited neurodegenerative diseases of this type. The CAG repeat expansion in the mutated gene leads to a<br />

polyglutamine stretch in the htt protein and thus causes alterations in protein function and processing. Expanded htt fragments<br />

localize to the nucleus and there disrupt transcription. Medium spiny neurons in the striatum of affected individuals were shown<br />

to be especially vulnerable to these effects. This study aims to investigate the interaction of mutated htt and peroxisome<br />

proliferator activated receptor (PPAR) δ, a nuclear receptor involved in the recently highlighted PGC-1α pathway and therefore<br />

in the brain’s energy metabolism.<br />

Materials and Methods:<br />

We performed cell culture experiments in HEK293 cells, C2C12 cells and Hdh striatal-like neurons derived from HD knock-in<br />

mice, including transient transfections of htt and PPARδ followed by co-immunoprecipitation experiments. To delineate the<br />

interaction domain on PPARδ, we generated PPARδ truncation constructs that were transfected into cells or used for in vitro<br />

production of recombinant proteins. Co-immunoprecipitation of endogenously expressed proteins was also performed,<br />

particularly in the HdH striatal-like neurons. The transcriptional function of PPARδ was further investigated by performing<br />

chromatin immunoprecipitation (ChIP) of the protein followed by real-time qPCR. These experiments were performed to<br />

validate the ChIP procedure and the antibody to be used in a ChIP-Seq study.<br />

Results/ Conclusions:<br />

Within the family of PPAR nuclear receptors, the δ subtype exhibits the highest expression level in the brain. We demonstrated<br />

a physical interaction between PPARδ and the htt protein. Furthermore, we showed that this interaction is not affected by the<br />

CAG repeat expansion in htt, and is independent of the presence of PPARδ ligand. The exact region of the PPAR protein<br />

mediating its interaction with htt protein and whether the interaction is direct or indirect remain to be determined. Nonetheless,<br />

these results provide support for the involvement of PPARδ in HD pathogenesis and might suggest a new therapeutic target for<br />

the treatment of HD.<br />

Note: Anne Buttgereit received funding for her <strong>BMEP</strong> time in the U.S. from the DAAD.<br />

<strong>BMEP</strong> Students’ conference <strong>2012</strong>


JAN CZOGALLA<br />

Email: jan.czogalla@gmail.com<br />

Home Institution: Westfälische Wilhelms Universität, Münster<br />

Host Institution:<br />

University of California San Diego, San Diego, CA<br />

Research Mentor:<br />

Volker Vallon, M.D., Professor of Medicine and Pharmacology,<br />

University of California San Diego<br />

Personal Reaction to the U.S. Experience:<br />

I found a very motivated team in a great lab, situated in one of the most rewarding areas for biomedical research one can find:<br />

Whenever we wanted to test a new method or asked a new question, the expert in that field happened to be just two doors away.<br />

My experience further encourages me to follow this path and to stay in biomedical research.<br />

Greatest Difficulties Encountered:<br />

Certainly acquiring the DS-2019 in time and ahead of my stay, and meeting the requirements of overwhelming bureaucracy<br />

(such as clearance by the FBI) at the VA Medical Center in San Diego.<br />

Most Humorous Incident:<br />

Many humorous incidents were created by the fact that the whole lab team was from all over the world (11 people, of whom 3<br />

were "native" Americans), and small misunderstandings were the rule rather than the exception. However, all those superficial<br />

misunderstandings in the end were always resolved and led to a deeper (cultural) understanding.<br />

Helpful Hints for Future Students:<br />

I think my experience was certainly enhanced by the fact that I was working in a smaller lab. While looking for publication<br />

output and great names (which I, of course, also did), don't forget to make sure the person who will be your host really cares for<br />

you while you are here.<br />

Try to acquire your Social Security Number as fast as possible, as it will help you numerous times.


Abstract on Research Topic – Jan Czogalla<br />

Title: Physiological Roles for the CaSR in the context of the JGA<br />

Authors: Jan Czogalla, Takahiro Masuda, Maria Gerasimova, Michael Rose, Volker Vallon<br />

Institution: Department of Nephrology and the Veterans Administration San Diego Healthcare System, University of<br />

California San Diego, San Diego, CA<br />

Introduction:<br />

The CaSR (Calcium sensing Receptor) is a G-protein-coupled receptor (Gi), consisting of 1078 amino acids, spanning the<br />

cellular membrane seven times and forming two large extracellular loops ("Venus-fly-trap-motif"). It was molecularly<br />

identified in 1993 by Brown et al. (Nature. 1993 Dec 9; 366(6455): 575-80.). One major physiological role is the regulation of<br />

extracellular calcium levels via parathyroid hormone. Activation causes Ca2+-influx into the cell by activation of the<br />

phospholipase-c pathway, inhibiting adenylyl cyclase V and thus decreasing cAMP formation. The CaSR is highly expressed<br />

throughout the tubular system of the kidney, and plays a role in kidney calcium homeostasis. Recently, it has been shown that<br />

CaSRs are also present in the juxtaglomerular cells of mice (Ortiz-Capisano et al., Hypertension 2007; 50:737–743.) They are<br />

thought to promote the calcium paradoxon in the kidney (increasing extracellular Ca2+ levels cause decreasing extracellular<br />

renin levels). However, the physiological role has not yet been proven.<br />

Materials and Methods:<br />

We utilized male C57/Bl6 cre/lox mice (ages 120-230 days, weight 23-41g). The cre-recombinase was active in the promoter<br />

region of the renin gene, activating cre in the JGA cell. The CaSR was floxed. Thus, CaSR deletion promoted by cre<br />

recombinase activity in the JGA cell resulted. These mice were then compared to wild type littermates.<br />

We used different NaCL diets (0.01 %, 0.8% and 4%, Teklad) and measured basal bodyweight, food uptake and water uptake.<br />

Diets were then over crossed, and changes noted. All the while, blood pressure, heart rates and urine electrolyte excretion was<br />

measured. Renin blood levels under different salt diets were measured by RIA assay (Diasorin). We then used several ways of<br />

in vivo stimulation of renin release (Isoproterenol, Enalapril, Furosemide) as well as direct stimulation of the CaSR by Ca2+<br />

and the specific CaSR agonist R-568 and measured resulting changes in renin release. Furthermore, renin mRNA levels were<br />

determined and bio impedance studies were conducted for comparison of total body water, extra- as well as intracellular body<br />

water and body fat content of the mice.<br />

Results/ Conclusions:<br />

We were able to prove the successful knockdown of the CaSR in the JGA cell of our mice. Selective CaSR deletion resulted in<br />

a renal phenotype, which was indifferent to wild type animals under basal conditions. However, diet changes resulted in<br />

difficulties in the compensatory mechanisms of blood pressure and heart rate, compared to physiological response in the wild<br />

type animals. These differences were strongly pronounced in an acute setting (8-48h after salt intake), and were followed by<br />

partial compensation over time (up to six days). Our results suggest a possible involvement of the CaSR in blood pressure<br />

autoregulation via the regulation of renin release.<br />

Note: Jan Czogalla received funding for his <strong>BMEP</strong> time in the U.S. from DAAD.


KONSTANTIN DEUTSCH<br />

Email:<br />

konstantin.deutsch@stud.mh-hannover.de<br />

Home Institution:<br />

Medizinische Hochschule Hannover<br />

Host Institutions:<br />

The Jackson Laboratory, Bar Harbor, ME and<br />

Mount Desert Island Biological Laboratory, Salisbury Cove, ME<br />

Research Mentors:<br />

Prof. Dr. Hermann Haller, Adjunct Professor, MDIBL<br />

Prof. Dr. Mario Schiffer, Adjunct Professor, MDIBL<br />

Dr. Ron Korstanje, Senior Research Scientist, The Jackson Laboratory<br />

Personal Reaction to the U.S. Experience:<br />

By pure coincidence I happened to have visited Bar Harbor for vacations two years before I came here, so I already knew what<br />

to expect: A small and exceptionally neat town on Mount Desert Island, surrounded by the Atlantic Ocean and home to Acadia<br />

National Park and its stunning scenery. The population of Bar Harbor changes drastically between high season in the summer<br />

months and fall and the off-season winter. In the summer and during fall with its world famous Indian Summer, the town was<br />

vibrant, always filled with people and the destination of at least one cruise ship a day. It really helped me a lot to get settled<br />

here with so many – mostly touristy – things to do in the summer, essentially getting to live where other people spend their<br />

vacations. I am very glad I had this time to get familiar with Bar Harbor and the people here, because the winter version of Bar<br />

Harbor looks much different – a tiny town, with temperatures around -10° C and nobody on the streets. But by that time I<br />

fortunately knew a lot of people around town, so I didn’t have to be afraid of being too lonely in what then was a somewhat<br />

lonesome place. Both labs I worked in gave me excellent opportunities to work in a highly professional environment on my<br />

research project and develop my own new ideas to always take this project one step further. I met amazing people, both bright<br />

scientists and great new friends. I am extremely grateful I was able to get the chance of having this unique experience.<br />

Greatest Difficulties Encountered:<br />

When I arrived at MDIBL in July, I was first housed in what I had been told was a “rustic cottage”. My housemates and I were<br />

able to turn our little cabin in the woods into a nice cozy place, but apparently we humans weren’t the only ones who really<br />

appreciated a warm and dry house. About two weeks after we first moved in, bats started visiting us on a nightly basis. I am –<br />

to be perfectly honest – not precisely the biggest fan of bats, so it really upset me to wake up from the noise of a bat being<br />

trapped under our roof every night. Thankfully, my PI, Prof. Schiffer, told me about that problem before, so I was well prepared<br />

and brought a mosquito net from Germany, which fortunately kept the bats out of my bed. Apart from my phobia, the greatest<br />

difficulty was – as usual – getting my visa and getting through immigration with it. Being escorted to secondary inspection in<br />

front of all the people waiting in the immigration hall can be quite embarrassing.<br />

Most Humorous Incident:<br />

The most humorous incident is not really a single incident. I guess, it is my time with the bats as well. Apparently, everybody<br />

who came to MDIBL from Hannover Medical School before us, including our PIs, stayed in that cottage as well and made it<br />

out of there well and alive. So whenever I started complaining about those bats, people would start to laugh about me for being<br />

so whiny. Looking back, I really do smile about it as well, it wasn’t that bad after all in retrospect.<br />

Helpful Hints for Future Students:<br />

Everybody writes that and everybody is right: Start taking care of your visa stuff early!<br />

Open a German bank account with which you can withdraw money free of charge in the US (KfW, comdirect,…), as your<br />

scholarship will be wired to a German bank account.<br />

Also, try to open an American bank account because if you want to buy stuff online, you often have trouble using your German<br />

credit card, since the card data is verified by address verification, which just doesn’t work with cards issued by German banks.<br />

Last but not least: Your time in the US will be much more enjoyable if you don’t get upset by “typically” American stereotypes<br />

you may find annoying. Just shrug your shoulders, laugh and remember – there’s probably a whole lot of people who are<br />

annoyed by your own habits. They tolerate you as well.


Abstract on Research Topic – Konstantin Deutsch<br />

Title:<br />

The Role of Kynurenine 3-monooxygenase in the function of the glomerular filtration barrier function<br />

Author:<br />

Konstantin Deutsch<br />

Institutions:<br />

The Jackson Laboratory, Bar Harbor, ME, USA<br />

Mount Desert Island Biological Laboratory, Salisbury Cove, ME, USA<br />

Introduction:<br />

Kynurenine 3-monooxygenase (KMO) is an NADPH-dependent flavin monoxygenase known to function as the catalyst in the<br />

hydroxylation of L-Kynurenine to form L-3-Hydroxykynurenine in the tryptophan breakdown. While KMO is almost<br />

exclusively linked to neurological phenotypes, metabolites of the KMO-mediated hydroxylation as well as its alternate<br />

pathways are known to be altered in plasma and urine during kidney failure.<br />

KMO was identified as a potential contributor to proteinuria by a genome-wide association study that mapped loci affecting the<br />

albumin/creatinine ratio (ACR) in outbred mouse strains. Among the strongest SNP associations found was a region on<br />

chromosome 1 of a cross between the mouse strains C57BL/6J and NZM2410/J (NZM). In this region KMO was identified as<br />

the strongest candidate gene.<br />

Materials and Methods:<br />

A KMO knockdown was performed in zebrafish (Danio rerio) by blocking its translation with an ATG-morpholino, an oligo<br />

which binds to the start codon of the coding gene. The morpholino was injected into the zebrafish eggs while they were in a<br />

one- or two-cell stage.<br />

As a first evaluation of the role of KMO in the glomerular filtration barrier, zebrafish embryos were monitored for the<br />

development of edema over 120 hours post fertilization (hpf). The phenotypes found were staged from P1 (=no edema) to P4<br />

(severe edema, life expectancy usually < 5 days). Two different kinds of functional assays were then carried out to determine<br />

whether proteinuria is the actual cause for the edema. The first assay was done by injecting an FITC-labeled dextran (70 kDa)<br />

into the cardinal vein of 48-hour-old embryos. A baseline fluorescence measurement was taken from the eye of every embryo<br />

24 hours after the injection; this baseline was compared to a second measurement after another 24 hours. A second functional<br />

assay used a transgenic zebrafish line that expresses green fluorescent protein (GFP) attached to a liver fatty acid binding<br />

protein (FABP) (78 kDa). Fluorescence measurements were taken from the eye at 96, 120 and 144 hpf and the mean<br />

fluorescence between the verum and control groups was compared. Electron microscopy was performed on glomeruli of<br />

zebrafish fixed at 120 hpf.<br />

NZM mice were obtained, as KMO for a QTL for elevated ACR was found in this strain, and urine and plasma samples are<br />

being collected. Upon development of proteinuria the mice will be sacrificed and kidneys will be taken for<br />

immunohistochemistry and expression analysis of KMO in proteinuric as well as healthy animals. Urine and plasma will be<br />

screened for altered levels of metabolites of the KMO hydroxylation and its alternate steps.<br />

Results/ Conclusions:<br />

The zebrafish phenotyping, functional assays and electron microscopy show strong evidence that knocking down KMO in<br />

zebrafish leads to renal damage, including podocyte effacement and proteinuria, which supports the hypothesis that a SNP in<br />

the gene coding for KMO would lead to an elevated ACR.<br />

The mouse experiments are ongoing, as the animals have not yet developed an elevated ACR.<br />

Note: Konstantin Deutsch received funding for his <strong>BMEP</strong> time in the U.S. from DAAD.


MEIKE GÖLZENLEUCHTER<br />

Email: meike.goe@googlemail.com<br />

Home Institution: Charité - Universitätsmedizin Berlin<br />

Host Institution: Mayo Clinic, Rochester, MN<br />

Research Mentor:<br />

Andreas. S. Beutler, M.D., Assistant Professor of Oncology and Anesthesiology<br />

Personal Reaction to the U.S. Experience:<br />

The friendliness of the people struck me from the very first day. The shuttle from Minneapolis to Rochester dropped me<br />

directly in front of my house, just because the driver saw my two heavy bags. I loved the typical wood house I shared with my<br />

two American roommates, especially the swinging bench that we had on our porch! During the weekend I spent hours there<br />

having breakfast, reading and listening to the guitar my roommate was playing inside. After six months and with the beginning<br />

of the spring, I finally got to appreciate the calmness of Rochester.<br />

My work experience was very formative, with an alternating course between excitement and frustration. The more I got into a<br />

subject, the more questions crossed my mind, with the answers further leading to new questions, and to finally realizing that<br />

everything was much more complicated than it seemed in the beginning! The atmosphere in my office was great. Due to the<br />

close teamwork with the bioinformaticians I gained great insights into the handling of sequencing data and statistics!<br />

I still think that Rochester is more a complex of Mayo buildings, rather than a city. However that also has some advantages, at<br />

least if you only live there for a year. Since there is not much distraction, you can entirely focus on your research, live healthier<br />

and save money.<br />

Greatest Difficulties Encountered: Getting used to the uniformity of the city, where it seems that everybody is an employee<br />

of the Mayo Clinic.<br />

Most Humorous Incident: In the supermarket there are always lots of employees asking you how you are doing and if you are<br />

finding everything that you need. Once I asked a young employee in his mid-twenties if he could tell me where to find some<br />

rosemary. He stared at me for a couple of seconds and remained silent. I started smiling and carefully asked, “Oh, you don't<br />

know what rosemary is?” Embarrassed, he smiled and said, “No Ma'am, I'm sorry. Most people here don’t cook very often.”<br />

Helpful Hints for Future Students:<br />

- I found my shared house through the Mayo Clinic mailing list. In addition to craigslist it’s a good option (I have been living<br />

with 2 Ph.D. students for 12 months and don’t even have a contract!)<br />

- If you don’t plan to buy a car, get a bike! Grocery shopping becomes much easier.<br />

- Mayo Clinic has its own gym (Dan Abraham Healthy Living Center). It becomes cheaper the more often you go.<br />

- Minneapolis offers a lot of good concerts. You should also have a drink in one of the rooftop-bars in the Uptown area.<br />

- The people here are extremely friendly and everybody will be happy to help.


Abstract on Research Topic – Meike Gölzenleuchter<br />

Title: Methylome-transcriptome analysis of different tissues in the rat<br />

Author: Meike Gölzenleuchter<br />

Institution: Department of Oncology, Mayo Clinic, Rochester, MN, USA<br />

Introduction:<br />

Understanding the role of DNA methylation whether in development, gene expression or disease requires insights into the<br />

frequency, distribution and dynamic of these epigenetic alterations. Tissue-specific differentially methylated regions (t-DMRs)<br />

have therefore been the focus of interest of many epigenetic studies over the past few years. However, the relationship between<br />

t-DMRs and tissue-specific gene expression remains ambiguous. In somatic mammalian tissues, DNA methylation occurs<br />

almost exclusively at CpG sites. Many techniques employed to detect altered methylation patterns have been restricted to the<br />

analysis of CpG sites in targeted genomic regions, such as promoters. Here we performed Reduced Representation Bisulfite<br />

Sequencing (RRBS) on the DNA of different tissues of the rat and provide a genome-wide DNA methylation map with<br />

nucleotide resolution for each. The main goal of the study is to find a relationship between t-DMRs and gene expression.<br />

Materials and Methods:<br />

Six different tissues (muscle, spleen, liver, spinal cord, dorsal root ganglion from L4 and from L5 level) from the inbred Brown<br />

Norway rat strain were included in the methylome-transcriptome analysis. For each tissue, two biological replicates were<br />

available. For the methylation analysis DNA was extracted from each tissue and Reduced Representation Bisulfite Sequencing<br />

(RRBS) performed. Total RNA of the same tissues was extracted and sequenced on an Illumina HiSeq 2000 platform.<br />

Results/Conclusions:<br />

For the methylation analysis, we included all CpGs that were common to all samples and had at least a tenfold coverage in each<br />

tissue. This resulted in 998,401 CpGs, corresponding to 2% of all CpG sites in the rat. The methylations patterns between<br />

biological replicates showed high correlation (r > 0.97 for all pairs). On the contrary, alterations in the methylome distinguished<br />

the six tissues under focus. In which genomic areas these tissue-specific differentially methylated regions (t-DMRs) are<br />

preferentially located and how they are related to gene expression is still pending.<br />

Note: Meike Gölzenleuchter received funding for her <strong>BMEP</strong> time in the U.S. from the DAAD and the Mayo Foundation.<br />

Konstantin Deutsch and Dr. Ron Korstanje in front of the Nobel Mouse Wall at Jackson Laboratory, Bar Harbor, ME


TOBIAS GREVE<br />

Email: greve.tobias@googlemail.com<br />

Home Institution:<br />

Technische Universtität München; Ludwig-Maximilans-Universität München<br />

Host Institution:<br />

University of California, San Francisco, CA<br />

Research Mentor:<br />

Robert Blelloch, M.D., Ph.D., Associate Professor, Department of Urology,<br />

University of California, San Francisco, CA<br />

Personal Reaction to the U.S. Experience:<br />

In retrospect, after the seven months I have been living here the governing title of this experience would certainly be<br />

“diversity”, as people, opinions and lifestyles vary so extremely in the United States. This was certainly underscored by living<br />

in a shared apartment for 5 people with Chinese students – making it a real intercultural experience.<br />

Apart from that, San Francisco is surely one of the most progressive places in the US and people are, in general, low key and<br />

very life-savoring. At the same time, I have rarely encountered a laboratory with such hardworking and focused members, a<br />

fact I really appreciated.<br />

For all those reasons, I am more than glad to have had the opportunity to work at UCSF. I especially want to thank my host<br />

tutor Dr. Blelloch, my German tutors Drs. Neth and Jochum and the IALS for their great support.<br />

Greatest Difficulties Encountered:<br />

Finding an affordable apartment in San Francisco with just 5 days to go before beginning my laboratory work was not easy.<br />

Craigslist and Padmapper are a great help though.<br />

Most Humorous Incident:<br />

My Chinese roommates’ cooking was a continuous humorous incident. Mostly my reaction to their very exotic dishes like<br />

chicken feet, chicken gizzard or jellyfish, all of which I tried, contributed to a very cheerful experience.<br />

Helpful Hints for Future Students:<br />

Getting the DS2019 in time is certainly a major priority. If time is short, the <strong>International</strong> Office of the respective institution<br />

can supply the DS2019 number before sending out the actual document. This enables reservations to be made with the embassy<br />

in time. Beware: there is no “emergency” visit possible with the consulate if there are still appointments available in other cities<br />

across Germany – a fact I experienced myself when I had to go to Frankfurt for a five-minute interview at a counter.


Abstract on Research Topic – Tobias Greve<br />

Title: microRNA-294 targets key cellular pathways to promote pluripotency in mouse embryonic fibroblasts.<br />

Authors: Tobias Greve, Robert Judson<br />

Institution: Department of Urology, Univ. of California, San Francisco, CA<br />

Introduction:<br />

MicroRNAs (miRNAs) are 22 nt non-coding RNAs that regulate expression of downstream targets by mRNA destabilization<br />

and translational inhibition. A large number of eukaryotic mRNAs are targeted by miRNAs, with many individual mRNAs<br />

being targeted by multiple miRNAs. Further, a single miRNA can target hundreds of mRNAs, making these small RNAs<br />

powerful regulators of cell fate decisions and broad cellular programs. Such regulation by miRNAs has been observed in the<br />

maintenance of the embryonic stem cell (ESC) cell cycle and during ESC differentiation. MiRNAs can also promote the<br />

dedifferentiation of somatic cells to induced pluripotent stem cells. During this process they target multiple downstream genes,<br />

which represent important nodes of key cellular processes.<br />

Previous work from my group showed that microRNA-294, a predominant microRNA present in ESC, is able to enhance the<br />

process of cell dedifferentiation towards ESC like induced pluripotent stem cells (iPSC). Following that observation, Robert<br />

Judson from my lab created a high-confidence list of potential miR-294 targets by comparing microrarray data and public target<br />

databases for miR-294. This led to a 60-target list for this specific microRNA. When knocking down each of these individual<br />

targets by siRNA, Robert Judson was able to show that a high number of those potential targets significantly enhance<br />

reprogramming as well, as assessed by GFP + colony count.<br />

Pathway enrichment analysis for those 60 targets was carried out by the bioinformatics corps at UCSF and revealed that those<br />

miRNA targets converge in regulating a small number of essential processes and pathways related to pluripotency and selfrenewal.<br />

My project was to verify the statistical results for two of these pathways: IGF/PI3K/Akt signaling and Wnt signaling.<br />

Materials and Methods:<br />

We used the original Yamanaka system for retroviral reprogramming of mouse embryonic fibroblasts (MEFs). Experiments are<br />

normally carried out in 96 well plates. Cells are transfected with different siRNAs and microRNAs during the course of<br />

reprogramming. Apart from assessing reprogramming efficiency and kinetics using a large-scale image analysis system called<br />

“InCell” and GFP-Oct4-MEFs, the plate was also used for immunofluorescence assays to assess Akt and Wnt activity.<br />

Results/ Conclusions:<br />

Experiments are to be carried out for three more months from now, but preliminary results verify the statistical approach by<br />

showing that miR-294: a) modulates Akt signaling by targeting PTEN and Akt1 and b) increases Wnt signaling activity as<br />

revealed by beta-catenin relocalization and luciferase reporter assay. These results corroborate the finding that Akt activation<br />

and Wnt activation increases reprogramming efficiency.<br />

Note: Tobias Greve received funding for his <strong>BMEP</strong> time in the U.S. from the DAAD.


TIMM HEINBOKEL<br />

Email:<br />

theinbokel@gmail.com<br />

Home Institution:<br />

Charité – Universitätsmedizin Berlin<br />

Host Institution:<br />

Brigham and Women’s Hospital, Harvard Medical School, Boston, MA<br />

Research Mentor:<br />

Stefan G. Tullius, M.D., Ph.D., FACS<br />

Chief, Division of Transplant Surgery & Director, Transplant Surgery Research<br />

Laboratory, Brigham and Women’s Hospital, and<br />

Associate Professor of Surgery, Harvard Medical School<br />

Personal Reaction to the U.S. Experience:<br />

Living in the U.S. is in so many ways part of living in any Western country, so that I did not experience anything even similar<br />

to culture shock during my stay. At the beginning, a lot of my cultural stereotypes seemed to be confirmed, but very quickly I<br />

realized that this vast, diverse and constantly changing nation cannot be summarized by one single notion; you will easily be<br />

able to prove and disprove all your prejudices.<br />

Very soon I was able to understand the allure that this country still has for so many people around the world. Many experiences<br />

at the hospital or on campus were simply humbling. Many of the promises this nation makes might not be kept to everyone<br />

anymore, but it is hard to imagine that this country will not reinvent itself one way or the other. Although a working health care<br />

system in the U.S. simply does not exist, some institutions seem to outshine everything. In fact, I was deeply impressed by this<br />

uncompromised striving for professionalism and perfection.<br />

Greatest Difficulties Encountered:<br />

I was able to experience a very competitive biomedical research system as an (thanks to the support of my mentor) innocent<br />

bystander. I saw the incredible potency, but also the brutality of this structure. Learning how research and the relations between<br />

its actors as a political and social system work was sometimes stressful, but always very instructive.<br />

And, of course, finding financial support and applying for a visa are probably among the most stressful aspects of this venture.<br />

Most Humorous Incident:<br />

It’s not exactly a humorous incident, but pretty absurd in its own way: the Department of Music decided to invite David<br />

Liebman over for a jazz residency, including a public master class. Suddenly, after going through a maze of rooms and halls, I<br />

found myself in one room with only fourteen others and this amazing saxophone icon.<br />

Helpful Hints for Future Students:<br />

You have to learn to rein yourself in. You will probably be very motivated when you arrive and at some point you will want to<br />

prove to yourself and your PI what a brilliant mind you are. But be patient and try to remind yourself again and again that<br />

research is just one aspect of your stay and that even if everything goes terribly wrong in the lab you will have a great<br />

experience to look back on for the rest of your life. Make small and well-planned steps and do not try to reinvent the wheel.<br />

Reward yourself when things go well and realize that there is no such thing as perfection and absolute truth in science. Do not<br />

work on weekends or after hours unless you really have to, and just call it a day when nothing seems to work out.<br />

Try to read a lot in order to get to know your field. Ask other lab members about their opinions on specific papers. Ask your PI<br />

if you could work on a review with him.<br />

Insist on having a well-defined project before you come to the US and do not chose your host institution solely based on<br />

reputation, but on the proposed project, foreseeable support and the things you can take out of it besides some lines in your CV.<br />

Don’t be too humble, and know your value and contribution to the lab. Definitely try to do a rotation.<br />

Boston and Cambridge are great, but they represent a very biased version of the U.S., so travel around. Try to experience your<br />

university, your city and your region in ways different than through biomedical research. Go the extra mile at the beginning to<br />

find some native-speaking roommates to live with.


Abstract on Research Topic – Timm Heinbokel<br />

Title: Old graft-derived dendritic cells evoke more potent alloimmune responses<br />

Authors: Heinbokel T, Oberhuber R, Boenisch O, Hock K, Elkhal A, Tullius SG<br />

Institution: Transplant Surgery Research Laboratory, Division of Transplant Surgery, Brigham & Women’s Hospital, Harvard<br />

Medical School, Boston, MA<br />

Introduction: In an attempt to meet the growing gap between demand and supply in transplantation medicine, transplantation<br />

of organs from old donors is more and more regarded as common clinical practice. In large-scale clinical studies, however, the<br />

use of these organs has been associated with increased frequencies of acute rejection episodes. We investigated the impact of<br />

donor age on recipient immune responses using a fully MHC-mismatched murine cardiac transplantation model.<br />

Methods/Results: Hearts from young (3 mo) or old (18 mo) C57BL/6 (B6) donor mice were grafted into young (3 mo) DBA/2<br />

recipients. Old hearts were rejected more rapidly than young hearts and H&E staining revealed higher rejection scores.<br />

Furthermore, recipients of old allografts showed more potent systemic immune responses with increased frequencies of<br />

alloreactive IFN-γ producing cells as well as higher percentages of CD8+ effector and CD8+ IFN-γ+ T cells.<br />

To determine whether the overzealous immune response observed after transplantation of old organs is due to enhanced direct<br />

allorecognition promoted by aged graft-derived passenger leukocytes or increased immunogenicity of the aged parenchyma<br />

itself, chimeric animals were generated by transplanting bone marrow from young B6 mice into lethally irradiated old or young<br />

B6 mice. Transplantation of chimeric (i.e. old or young parenchyma with young passenger leukocytes) hearts into young<br />

DBA/2 mice resulted in comparable survival rates, rejection scores and recipient systemic immune responses.<br />

CD11c+ dendritic cells (DCs) have been shown to be key players in direct allorecognition. To investigate in-depth their<br />

relevance among passenger leukocytes in old grafts, depletion of DCs was performed in donors prior to transplantation using<br />

liposomal clodronate. Following transplantation of old or young DC-depleted B6 cardiac allografts into young DBA/2 animals,<br />

survival rates, rejection scores and systemic immune responses were similar between groups.<br />

Finally, priming capabilities of flow-sorted splenic DCs were characterized. DCs from old B6 mice induced higher proliferative<br />

responses and higher frequencies of IFN-γ producing cells after incubation with allogeneic DBA/2 splenocytes in vitro.<br />

Conclusion: These results demonstrate the importance of graft-derived leukocytes and particularly DCs for the clinical findings<br />

we were able to replicate in our model. They highlight the relevance of age-adapted immunosuppression and point to<br />

opportunities for optimization of organ allocation and development of donor pretreatment therapies.<br />

Note: Timm Heinbokel received funding for his <strong>BMEP</strong> time in the U.S. from DAAD and Stiftung Charité.


ALINA HILGER<br />

Email: alina_hilger@hotmail.com<br />

Home Institution: University of Bonn, Medical School<br />

Host Institution: University of Michigan, Department of Pediatrics<br />

Research Mentors: Friedhelm Hildebrandt, M.D., Heiko Reutter, M.D.<br />

Personal Reaction to the U.S. Experience:<br />

I do not think I can say anything about the U.S. in general. It is a very multifaceted country and so are the people. Speaking of<br />

the people from the Midwest and especially the small city of Ann Arbor, packed with over 40,000 students, I can only say that I<br />

found a lot of friendly, crazy, open minded, always helpful and very good friends here. These people hate prejudice and<br />

everybody is welcome. The mixture of such people and my Lab, with its friendly working atmosphere, made my time here<br />

great – an unforgettable experience!<br />

Greatest Difficulties Encountered:<br />

The greatest difficulty was definitely finding a place to live because I started in October one month after the semester had<br />

started, meaning that all leases were taken. Eventually I was lucky and got a room with a friend of a former student in my lab.<br />

I may also want to mention that “doing my taxes” was only possible with the help of our Administrator and took me almost 2<br />

days!<br />

Most Humorous Incident:<br />

I could name a lot of things here, but since I have to decide on one, I have chosen an incident that started when I got an email<br />

that contained a tornado warning. We were all totally excited since there are six of us Germans in the lab not familiar with<br />

things like tornados. In the end, we all were sitting in the room with the biggest windows waiting to see a tornado as a once-in –<br />

a-lifetime experience, making plans about how to flee to a room without windows if it came towards us. I guess that is what<br />

happens when you put together a couple of curious young researchers, their weather-addicted supervisor and a tornado warning.<br />

“Oh those Germans,” as a friend of mine often says.<br />

The tornado stopped 10 miles away from Ann Arbor, but we had two great hours watching the sky and the weather forecast<br />

instead of our research sequences.<br />

Helpful Hints for Future Students:<br />

Definitely get a driver’s license and a Social Security number! (Without these you are no more than a tourist in the U.S.)


Abstract on Research Topic – Alina C. Hilger<br />

Title: Identification of CAKUT Causing Genes<br />

Authors: Alina C. Hilger 1 , Pawaree Saisawat 1 , Daw-Yang Hwang 1 , Stefan Kohl 1 , Heiko M. Reutter 2 , Friedhelm Hildebrandt 1<br />

Institution: 1 Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA, Howard Hughes Medical<br />

Institute; 2 Department of Human Genetics, University of Bonn, Bonn, Germany<br />

Introduction: The phenotypic spectrum of congenital abnormalities of the kidney and urinary tract (CAKUT) ranges from<br />

vesicoureteral reflux to renal agenesis and is the most frequent cause of chronic kidney disease in children. Several mouse<br />

models suggest underlying single-gene-defects, of which only a few could be identified in humans so far.<br />

Materials and Methods: Based on the hypothesis that an individual with an autosomal recessive disease will very likely be<br />

identical by descent for the mutated allele, we determined by homozygosity mapping the genomic regions that occur<br />

homozygously in our patients. Whole exome capture was performed and all genes within the homozygous regions were<br />

analyzed. Mutations, identified with the combination of those methods, were verified by Sanger sequencing.<br />

Results/ Conclusions: In 3 individuals with CAKUT phenotype, we identified a homozygous mutation 1046G>A, leading to<br />

an amino acid change R469H in the TNF receptor associated protein (TRAP1). Further studies will be performed to decide<br />

whether mutations in TRAP1 are responsible for the CAKUT phenotype.<br />

Note: Alina C. Hilger received funding for her <strong>BMEP</strong> time in the U.S. from the DAAD.<br />

Final discussion, Students’ conference <strong>2012</strong>


MATTHIAS HOEPTING<br />

Email: matthias.hoepting@gmx.de<br />

Home Institution: Hannover Medical School<br />

Host Institution: University of Michigan, Ann Arbor, MI<br />

Research Mentor: James L.M. Ferrara, M.D., Professor of Pediatrics and<br />

Internal Medicine, Department of Hematology and Oncology, Director of Bone<br />

and Marrow Transplantation Program<br />

Personal Reaction to the U.S. Experience: The first experience that sticks in my mind is wandering through the streets of Ann<br />

Arbor on one of my very first days here, just to get to know the city. At a cross-walk I took out a map to orientate myself again,<br />

but before I opened it a woman shouted from the other side of the street and asked if I needed some help. That is a good<br />

example of what I experienced here a lot of times: Americans are very friendly towards foreigners.<br />

Ann Arbor is not a very big city, but has a big university and an even bigger football stadium, which offers space for more<br />

people to watch a game than actually live in Ann Arbor…and surprisingly it is usually full of people.<br />

But that is only one of the astonishing things to discover in this wonderful city. Besides that it is a very international place. I<br />

guess I met more people from foreign countries than from the U.S., so going to Ann Arbor not only gives you the opportunity<br />

to get to know the American culture, but also provides a lot of opportunities to get smaller or bigger insights into a wide variety<br />

of cultures.<br />

That was also reflected in the people in my lab. There were nine individuals from five different countries and working there<br />

was just great. At the beginning I had to get used to such a wide range of accents, but in the end it was no problem at all. Even<br />

though it occasionally took some time to obtain satisfying results, everybody was always willing to help and to discuss how to<br />

improve certain experiments.<br />

Greatest Difficulties Encountered: The most difficult thing was to get all the paperwork done that was required to get my<br />

visa. But somehow everything worked out in the end.<br />

Most Humorous Incident: A friend from Germany and I were invited to my Professor’s for Thanksgiving. After a while my<br />

Professor said, ”Now I’d like to ask the first serious question of this evening - what do you think about Greece?” My friend<br />

didn’t get the point and answered with the most innocent face, “The musical?”<br />

Helpful Hints for Future Students: Try to apply for everything that requires paperwork as soon as possible and use craigslist.<br />

You can find almost everything there. Try to visit some other cities.


Abstract on Research Topic – Matthias Höpting<br />

Title: Pathophysiology in Gastrointestinal Graft versus Host Disease<br />

Authors: Matthias Höpting, Dongchang Zhao, James L.M. Ferrara, M.D.<br />

Institution: Department of Pediatrics, Hematology/Oncology, University of Michigan, Ann Arbor, MI<br />

Introduction: Graft versus Host Disease (GvHD) is a major complication of hematopoetic stem cell transplantation and causes<br />

a high rate of non-relapse mortality. The most affected organs are skin, liver and gut. Recently, regenerating islet-derived<br />

protein 3alpha (Reg3α) has been discovered as a serum biomarker for gastrointestinal (Gi-)GvHD, which is able to distinguish<br />

between non-GvHD and GvHD enteritis.<br />

The murine homolog of Reg3α is Reg3γ, a C-Type-Lectin, which is bactericidal against gram-positive bacteria. It is produced<br />

by paneth cells and enterocytes. Paneth cells also produce a large variety of other bactericidal peptides such as alpha-defensins<br />

and crypdins. Paneth cells reside in the crypts of Lieberkuehn in close proximity to Leucine-rich repeat-containing G-protein<br />

coupled receptor 5 (LGR5) positive intestinal stem cells and provide their niche.<br />

IL-22 is mainly produced by RORγt positive innate lymphocytes and is a potent inducer of Reg3γ in the gut.<br />

The aim of this study is to investigate the role of Reg3γ and paneth cells in Gi-GvHD and finally to identify new treatment<br />

strategies.<br />

Materials and Methods: Either a radiated or an un-irradiated C57BL/6 to B6D2F1 bone marrow transplant mouse model was<br />

used to induce GvHD. Serum samples and samples of the gut were collected at distinct time points and analyzed using ELISA,<br />

qRT-PCR, H&E staining and immune histochemistry staining.<br />

Results/ Conclusions: Reg3γ serum levels are increased in mice with GvHD, similar to what is observed in patients.<br />

Surprisingly, Reg3γ mRNA expression in the ileum is decreased as well as cryptdin-1 mRNA levels. Paneth cell numbers are<br />

also decreased.<br />

These findings are true in unirradiated GvHD models. Thus these changes are at least partly related to the allogeneic reaction<br />

and not only to irradiation. Further experiments will be done to clarify the role of IL-22 and its sources in Gi-GvHD. The<br />

influence of Reg3 γ on the microbiome and its role in Gi-GvHD also needs further investigation.<br />

Note: Matthias Höpting received funding for his <strong>BMEP</strong> time in the U.S. from DAAD.


MARIE CHRISTINE HUPE<br />

Email: marie.ch.hupe@web.de<br />

Home Institution:Hannover Medical School, Hannover, Germany<br />

Host Institution: University of Miami Miller School of Medicine, Department of Urology,<br />

Miami, FL<br />

Research Mentors: Vinata B. Lokeshwar, Ph.D., Professor and Co-Director, Division of<br />

Urology Research, Department of Urology, Cell Biology and Anatomy, University of Miami<br />

Miller School of Medicine; PD Dr. med Axel Merseburger and Dr. med. Thomas Herrmann,<br />

Department of Urology and Urologic Oncology, Hannover Medical School<br />

Personal Reaction to the U.S. Experience:<br />

I had a very warm welcome in Miami. Everybody was highly supportive! My research mentor, all my colleagues in the lab, the<br />

landlord of my apartment, neighbors, and so on. Since I didn't have a car, they offered to drive me wherever I needed to go.<br />

This was very helpful, especially at the beginning, because there was a lot to manage, such as finding a nice apartment and<br />

applying for a Social Security number. They introduced me quickly to their friends and to other students. I felt very comfortable<br />

right away. Almost every American could tell me about their half or quarter European background. It surprised me that lots of<br />

them had been to Germany before and the majority had heard of Hannover. All in all, I experienced a lot of support and<br />

courtesy. I made some very good friends and I am very happy that I had the chance to work and live here. I will fondly recall<br />

my time in Florida with all its memorable moments.<br />

Greatest Difficulties Encountered:<br />

Fortunately, I didn’t have to face big problems. The beginning, with all its necessary procedures to “start life” here, was very<br />

busy. I had to find an apartment, as I hadn’t done it from Germany, apply for a Social Security number, attend the sessions for<br />

new employees, attend a health screening, provide everything for the tax documents, etc. But all of this was done within the<br />

first weeks, and then I could start to enjoy my life in Miami, the weather and the beaches.<br />

Most Humorous Incident:<br />

I had many funny situations, but to name just two:<br />

At the very beginning of my stay in Miami I was looking for the Apple store in a shopping mall because I was looking for the<br />

new iPad. I asked someone for the location of the Apple store. The guy didn’t understand me, so I said, “iPad, iPod, iPhone”.<br />

Still this guy didn’t understand me. I couldn’t believe that he didn’t know Apple. After a few seconds he said, “Ah, you mean<br />

Apple and iPad, iPod, iPhone?” He pronounced it only slightly differently. He explained to me where to go. Somehow I<br />

couldn’t find the store again, so I had to ask another person. Exactly the same thing happened to me. I just pronounced it a little<br />

differently and the people didn’t know what I was talking about! This was not very encouraging at the beginning. J<br />

Apparently, German must sound very angry to American people. Every time I spoke German, my friends here in Miami made<br />

grim faces and joked, “Why was I yelling at my German friends?”<br />

Does every American believe that David Hasselhoff is a famous singer in Germany???? Really?? I don’t know how often I had<br />

to answer this question. I still have to sing “I’ve Been Looking for Freedom” at a karaoke bar because of a lost bet.<br />

Helpful Hints for Future Students:<br />

- Get certified translations of your ”Abitur” and “Physikum”. You might have to show them several times at the<br />

beginning.<br />

- Get a Deutsche Bank check card, so you can withdraw money without paying fees at any ATM of Bank of<br />

America.<br />

- Open a bank account in the U.S. (e.g. Wells Fargo in Miami). It will make things a lot easier for you.<br />

- Get a driver’s license that you can use as your ID. It will ease things, too.<br />

- Use the off-campus housing database of your university to find a place to stay.<br />

- Share the WiFi network with one of your neighbors. You don’t have to set up your own account/ contract for<br />

everything.<br />

- Contact students that have been in the same lab or in the same city.


Abstract on Research Topic – Marie Christine Hupe<br />

Title: Targeting HA-HAase system in urological tumors<br />

Authors: Marie Ch. Hupe, Travis Yates and Vinata B. Lokeshwar, Ph.D.<br />

Institution: Department of Urology, University of Miami Miller School of Medicine, Miami, FL<br />

Introduction: Hyaluronic acid (HA) is a nonsulfated glycosaminoglycan. It is a component of the extracellular matrix, where it<br />

acts as a space-filling molecule and regulates cellular migration, adhesion and proliferation. It is synthesized by a family of HA<br />

-synthases (HAS 1, 2, and 3). Hyaluronidases (HAases) degrade HA into smaller fragments, some of which have been shown to<br />

be angiogenic. Cellular effects of HA are mediated through the HA receptors, CD44 and RHAMM. It has been shown that the<br />

HA-HAase system promotes tumor growth, angiogenesis and metastasis.<br />

Project 1: In vivo efficacy of 4-MU for the treatment of prostate cancer<br />

4-Methylumbelliferone (4-MU) is a HA synthesis inhibitor that is orally bioavailable and non-toxic. 4-MU is available as a<br />

health supplement in Europe and is consumed for improving liver health. We examined the antitumor activity of 4-MU in a<br />

transgenic mouse prostate model (TRAMP – transgenic adenocarcinoma of the mouse prostate). The TRAMP model goes<br />

through six stages of prostate cancer development and progression: normal, hyperplasia, prostatic intraepithelial neoplasia<br />

(PIN), well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma and metastasis. Cancer development in this<br />

model is driven by the proto-oncogene SV40 that is expressed only in the prostate.<br />

Materials and Methods: TRAMP positive mice were randomized into a vehicle group or a treatment group (n=12/group). The<br />

vehicle group was gavaged daily with a 2% sucrose solution and the treatment group with 4-MU (450 mg/kg) dissolved in 2%<br />

sucrose. Gavaging was started at 8 weeks of age (PIN stage). Depending upon the size of the tumor, as determined by<br />

abdominal palpation, the mice were euthanized between 26 to 28 weeks of age.<br />

Results: The prostate/tumor was >10 fold higher in the vehicle treated (VT) group (2.1g ± 3.1 g) than the 4-MU treated group<br />

(0.14g ± 0.03 g). In fact, the weight prostate weight in the treatment group was no different from that in normal mice 28 weeks<br />

of age. Consistent with the tumor weight, the mean weight of the VT mice was 2.3 g higher than that of the 4-MU treated mice.<br />

The tumor in VT mice had visually invaded seminal vesicles, and their weight was higher in the VT group than the 4-MU<br />

group. Histology of the prostate showed poorly differentiated tumors in all 12 control mice, with lack of any prostate glands.<br />

The tumors were also highly vascularized. However, in all 4-MU treated specimens, tumor was not visible, and histology<br />

resembled the PIN stage at which treatment started. Also, in 5 of the VT mice metastasis was visible in the lung, liver and<br />

kidney but none was visible in the 4-MU treated mice. We next analyzed prostate tissues from the VT and 4-MU groups by<br />

quantitative real time PCR for the markers: SV40, CD44, RHAMM, E-cadherin, β-catenin and ZEB2. Expression of SV40 in<br />

the prostates of VT and treatment groups was the same: 4-MU not inhibiting the proto-oncogene that drives the carcinogenesis.<br />

But the expression of CD44, RHAMM was downregulated in the 4-MU group. Furthermore, 4-MU increased expression of Ecadherin,<br />

inhibiting metastasis. 4-MU lowered expression of β-catenin and ZEB2, both known to increase metastasis. Serum<br />

and organ toxicity screening showed that all toxicity indicators were normal in the 4-MU group.<br />

Conclusion: Our study shows that 4-MU is an orally bioavailable and effective antitumor agent which inhibits the development<br />

and progression of prostate cancer in the highly aggressive TRAMP model.<br />

Project 2: HAS3 and UGT1A9 as new prognostic markers for metastasis in kidney cancer<br />

About 90% of all kidney tumors are renal cell carcinomas (RCC). Metastastic RCC is fatal, 2 years.<br />

Materials and Methods: We examined matched normal and tumor specimens from 86 RCC patients. Of these, 17 had<br />

metastasis and 69 were free of it at the time of data analysis (follow-up: 15.2 ± 8.8 months; median: 13.8 months). We analyzed<br />

the expression of HAS3 and UGT1A9 by quantitative real time PCR. UGT1A9 is an UDP-glucuronyl transferase, but its role in<br />

cancer is unknown.<br />

Results: HAS3 and UGT1A9 expression was 3-4-fold elevated in RCC tissues from patients who either had or developed<br />

metastasis when compared to those who did not. Marker efficacy analysis showed that the combined HAS3+UGT1A9 marker<br />

had 92.3% sensitivity, 80.3% specificity and 81.6% accuracy to predict metastasis. The multivariate analysis using the Cox<br />

model showed that the combined HAS3+UGT1A9 marker is an independent predictor of metastasis.<br />

Conclusion: HAS3 and UGT1A9 are potentially accurate predictors for metastasis in RCC.<br />

Note: Marie Christine Hupe received funding for her <strong>BMEP</strong> time in the U.S. from the DAAD.


CHRISTIAN JENG-SINGH<br />

Email: cetchi@hotmail.de<br />

Home Institution: Medizinische Hochschule Hannover<br />

Host Institution: Mayo Clinic, Rochester, MN<br />

Research Mentors: Andreas Beutler, M.D. & Josef Pleticha, M.D., Department of<br />

Oncology and Anesthesiology.<br />

Personal Reaction to the U.S. Experience: Rochester, MN is a very small town in the Midwest. Due to Mayo Clinic it has its<br />

own <strong>International</strong> Airport where people from all over the world fly in to seek medical treatment. Minnesotans are very friendly,<br />

down to earth and kind-hearted. If you have any problems they will try to help you. There is a shuttle connection to<br />

Minneapolis, which goes back and forth on a hourly basis. So whenever you feel stuck here you can go up to the Twin Cities –<br />

Minneapolis and Saint Paul. However, when you have some spare time, you should travel and see the beauty and diversity of<br />

the U.S. Throughout the year I gained a lot of personal experience. The people I met were amazing! Mayo Clinic attracts<br />

students and visiting scientists from all over the world, so you learn a lot about different cultures.<br />

Greatest Difficulties Encountered:<br />

Get the DSC-2019 as soon as possible... and arrange your visa by yourself!<br />

Most Humorous Incident:<br />

There were a lot of humorous incidents throughout the year. Can't think of anything in particular.<br />

Helpful Hints for Future Students:<br />

- Open a Bank account at Mayo Credit Union (Mayo has its own Bank). It is free of charge and you can keep the<br />

account beyond the year.<br />

- In the winter it gets really cold, -20° Celsius! So prepare yourself!<br />

- Try to find a room in a shared house. It is easier for you to learn about American culture and meet new people.<br />

- Take the written and driving test at the DMV office. It's really cheap and the license serves as an ID here.<br />

- Craigslist, Mayo Classified Ads (for buying cars or looking for accommodation).


Abstract on Research Topic – Christian Jeng-Singh<br />

Title: Gene therapy for chronic pain – targeting sensory neurons with rAAV<br />

Author: Christian Jeng-Singh<br />

Institution: Mayo Clinic Rochester, MN<br />

Introduction: The recombinant Adeno-associated virus (rAAV) vectors are some of the most promising agents used for gene<br />

delivery to the nervous system. A number of serotypes have been described, each of them showing a distinct transduction<br />

pattern within the nervous tissue. IT-catheterization has been an established route of delivery for many years but it leads to a<br />

wide distribution within sensory neurons, spinal cord, and brain.<br />

Peripheral nerve injection, however, targets sensory neurons more specifically without wide distribution within the CNS and<br />

thus constitutes one of the most safe and efficient approaches. Sala-Blanch X et al. Anesthesiology (<strong>2011</strong>) showed that there<br />

was no clinical evidence of nerve damage detectable following ultrasound-guided intraneural injections in sciatic popliteal<br />

block (SPB). So far, peripheral nerve injections with rAAV have a low transduction efficiency. Our goal is it to increase<br />

transduction efficiency of sensory neurons in small and large animals and hence make this route of administration more<br />

applicable. A low complication rate, fast recovery, and simplicity in performance capitalize the benefits of peripheral nerve<br />

injection and make it a suitable candidate for potential clinical trials. Ultrasound-guided nerve blocks are readily performed in<br />

the clinics. Based on these facts, we intend to optimize the needle design for peripheral nerve delivery of rAAV vector, and<br />

compare transduction rates of novel rAAV serotypes within peripheral nerve, dorsal root ganglia, and spinal cord following<br />

peripheral nerve injection.<br />

Materials and Methods:<br />

• Agarose gel injection to evaluate needle design and infusion rate and volume (convection enhanced delivery).<br />

• Male Sprague-Dawley rats and Domestic Pigs were injected with rAAV into peripheral nerves.<br />

• Fluorescence Microscopy (LSM) has been used to detect native eGFP. Immunohistochemistry staining for eGFP,<br />

qPCR<br />

• Von Frey Testing( Behavior Testing), Neutralizing Antibody Immunoassay,<br />

Results/ Conclusions:<br />

Research is still going on for the next couple of month. Based on preliminary data, we can report that new serotypes were found<br />

which are able to be retrograde transported and transduce sensory neurons. Currently we are trying to enhance transduction<br />

efficiency and hence make this route of administration more attractive.<br />

Note: Christian Jeng-Singh received funding for his <strong>BMEP</strong> time in the U.S. from the Mayo Foundation and DAAD.


JUDITH KASPER<br />

Email: judith.kasper@rwth-aachen.de<br />

Home Institution: RWTH Rheinisch-Westfälisch-Technische Hochschule Aachen<br />

Host Institution: USACH – Universidad de Santiago de Chile<br />

Personal Reaction to the Chile Experience:<br />

It was in every way, professionally and personally, a very enriching and memorable experience. I would gladly recommend this<br />

exchange to everyone who is interested in internal medicine, knows Spanish and is open to getting to know another culture and<br />

country so full of interesting history, beautiful landscapes and most of all friendly and hospitable people.<br />

Greatest Difficulties Encountered:<br />

Bureaucracy and slow communication, both with the University and the embassy/local civil and foreign affairs registration<br />

offices, made it a real challenge to get the student visa and various registrations in time, even though I started the application<br />

process one year before the exchange.<br />

Most Humorous Incident:<br />

A cultural city tour with two good friends and colleagues, both medical students and Global Health activists. We wandered<br />

through a great hall of antiques and found German novels from the last two centuries that proved the connection between our<br />

two countries far back but still felt so out of place to me in this Latin American ambience. Then we had traditional food (Pastel<br />

de Choclo) until our stomachs ached, and afterwards hung out in a city park full of different people to relax and talk about our<br />

plans for the future. In the end we adventurously climbed a hidden pathway to the roof top of one of the public hospitals to<br />

watch the city of Santiago de Chile and the sun set from up above.<br />

Helpful Hints for Future Students:<br />

Improve your language skills, especially clinical vocabulary, before taking off to Chile. Ask friends or colleagues to accompany<br />

you to the registration offices, particularly if your Spanish is not yet that fluent. If you like hiking or rock climbing, Chile is the<br />

perfect country for it – bring along your equipment! Last but not least, consider bringing along your bike or buy one once you<br />

are there. More and more biking lanes are opening in Santiago and it’s a nice alternative to public transport or car.


Abstract on Practical Work Experience – Judith Kasper<br />

Title: Four months of final year internship (internal medicine) in a public university hospital in Santiago de Chile<br />

Author(s): Judith Kasper, M.Sc. Global Health<br />

Institution: Medicina Interna, Hospital San José, Universidad de Santiago (USACH)<br />

General information: In Chile, medical studies comprise seven years in total, of which the last two are spent as interns in<br />

pediatrics, internal medicine, gynecology, surgery and rural medicine. Nurses undertake five years of university studies. In<br />

internal medicine at the Hospital San José, they are in charge of managing the wards which, with the exception of the<br />

cardiovascular ICU, comprise patients and doctors from different subspecialties. Interns and residents are assigned to a<br />

specialist and his/her patients. Technical equipment, laboratory tests and examination procedures are more accessible than in<br />

e.g. Bolivian or Peruvian public hospitals, but still limited logistically and restricted in numbers. Special procedures and<br />

therapeutic options, such as cardiovascular surgery or chemotherapy, have to be undertaken at other, partly private, facilities.<br />

There is only a certain amount of procedures “credit” each month. This often results in significant delay of urgently needed<br />

treatments. Coronary heart disease patients with imperative indication for operation, who only have public health insurance,<br />

regularly wait one to three months to be referred for bypass surgery to one of Santiago´s private hospitals.<br />

Clinical work: Within internal medicine, students rotate every two to three weeks from one subspecialty (gastroenterology,<br />

cardiology, pneumology, nephrology, neurology, basic health care and cardiovascular ICU) to the next. Approximately three<br />

patients are assigned to each intern, to be fully examined twice a day and managed in terms of diagnosis and treatment.<br />

Specialists expect interns to present patients each morning during rounds. Where possible, diagnosis, symptom development<br />

and a treatment plan have to be presented and defended. After lunch, students, residents and one specialist on shift are left to<br />

take care of patient treatment, exams, consultations and admissions from the emergency care unit. The other specialists then<br />

leave the hospital to see patients at their private practices or other private health institutions.<br />

Conclusions: Four months of internship were a good time to adapt to a different health system and the organizational structures<br />

of the hospital. After two weeks I started to take on responsibilities like my Chilean fellow students. Without the language skills<br />

I had acquired beforehand, this would not have been possible. While the scarcity of resources and delay in necessary tests or<br />

treatments often really made me appreciate our German public health care system, the fact that I was responsible for and in<br />

charge of my own patients allowed a different way of learning and helped put already acquired knowledge to practice.<br />

Global Health in Santiago de Chile<br />

While in Santiago, I used the time to contact fellow students of the Chilean ifmsa section who are engaged in Global Health<br />

teaching and conferences (1° Congreso de Salud y Pobreza, October <strong>2011</strong>, Santiago de Chile). We exchanged experiences and<br />

ideas on the matter and, although our educational and social systems differ a lot, did find many parallel problems, for instance<br />

the lack of Global Health Education in all health professions. At the same time, we agreed that in Chile, even more<br />

impressively than in Germany, everyday reality at public health institutions proves the importance and relevance of global<br />

public health topics, for example the social determinants of health; see also http://www.who.int/social_determinants/en/. Global<br />

Health courses in Santiago are presently made available by a small group of engaged specialists, residents and students at the<br />

Universidad de Chile and the Universidad Católica de Chile. At the last institution, I had the chance to visit one of the current<br />

interdisciplinary teaching projects called “Viviendas Saludables” (healthy living). The course takes undergraduate students<br />

from architecture and medicine to a poor district of the city, where a cooperating NGO (Non-Governmental-Organization) has<br />

already succeeded in establishing a network with the neighborhood associations. The project mainly helps students to get to<br />

know the reality of families living in this area. Students are to analyze the area with the help of maps and the images they gain<br />

during weekly visits, from both an architectural and a medical point of view. The main goal, however, is not to come up with a<br />

perfect rebuilding plan, but to learn to listen to people’s own ideas and wishes. Then, based on the ideas of the local inhabitants,<br />

plans for improvement should be made. Though the course outline might sound ambitious and a bit idealistic, I am convinced<br />

that it is doing a great job in bringing together a divided society. I think it is a start to make future professionals think beyond<br />

the boundaries of their discipline, and work with others on the base of mutual respect and tolerance.<br />

Note: Judith Kasper received funding for her <strong>BMEP</strong> time in Chile <strong>2011</strong>/12 from IALS/B.Braun Melsungen-Foundation.


JANA KLUKAS<br />

Email: janaklukas@web.de<br />

Home Institution: Medizinische Hochschule Hannover<br />

Host Institution: Mayo Clinic, Rochester, MN<br />

Research Mentor: Andreas S. Beutler, M.D.<br />

Personal Reaction to the U.S. Experience: Rochester, Minnesota is a small and quiet Midwestern town, which basically<br />

consists of Mayo Clinic, because almost everyone you meet here either works at Mayo Clinic or is a patient there.<br />

As a newcomer you will be integrated instantly into the Mayo Community and they will make you feel privileged for being part<br />

of something big and successful, where every goal is reachable by using the most recent techniques and innovations. Trying to<br />

set up my own project in the lab I learned a lot of different techniques, as well as how to solve problems autonomously, come<br />

up with my own ideas and realize them.<br />

What makes Mayo a very productive and inspiring work environment is that you are getting in touch with a lot of interesting<br />

people and cultures from all over the world, who are eager to work together and help each other. Hence I made some very good<br />

friends of different nationalities and backgrounds.<br />

Because in spring people already started to warn me of Minnesota's cold winters, I did not expect the summer in Rochester to<br />

be so sunny and warm. Perfect for bike tours and spending your free time at one of the surrounding lakes! Sometimes I got the<br />

feeling that I had to escape small town life. Therefore I spent some weekends in Minneapolis and Chicago. Most exciting was<br />

my couchsurfing trip through California, where I surfed not only my hosts’ couches, but also the Pacific Ocean, which was a lot<br />

of fun.<br />

Greatest Difficulties Encountered: Because most of the time experiments do not work out on the first try, I had to increase<br />

my frustration tolerance. I am not a patient person.<br />

Living in the US without a car and trying to go grocery shopping etc. with your bike. Watch out if you get directions from<br />

google maps to find a restaurant or a store: you might end up on a highway without a trail for pedestrians or bikes. Anyway, as<br />

a cyclist you are a rare species on Rochester's streets.<br />

Most Humorous Incident: I knew that a lot of Americans are not big fans of fresh fruits and vegetables, but when the guy at<br />

the checkout counter of the grocery store looked very confused and helpless at my mangoes and then asked me if they were<br />

apples, I could not help laughing.<br />

Helpful Hints For Future Students: Try the Salty Caramel ice cream at Flappdoodles Homemade Ice Cream! Work hard to<br />

save some free time to travel through the US.


Abstract on Research Topic – Jana Klukas<br />

Topic: Epigenetic Profiling of Pain and Analgesic Drug Activity<br />

Author: Jana Klukas<br />

Institution: Department of Oncology, Mayo Clinic, Rochester MN, USA<br />

Introduction: Chronic pain is among the most frequent medical problems affecting 50 million patients and incurring costs<br />

of > $100 billion/year in the US alone. Peripheral nervous system (PNS) dysfunction is known to contribute to chronic<br />

pain but the inciting molecular mechanisms are not fully understood. Treating chronic pain is challenging because the origin is<br />

frequently not clear and a satisfying reduction of pain level cannot be achieved with current treatment methods.<br />

Recently, the host laboratory demonstrated widespread gene expression changes in the PNS in chronic pain with concomitant<br />

alterations in DNA methylation. The hypothesis underlying my research is that transcriptomic reprogramming is due to<br />

epigenetic alterations, specifically DNA methylation or hydroxymethylation.<br />

A number of current studies found a variety of small molecules capable of inhibiting the main enzyme initiators of those<br />

epigenomic changes. Therefore we intend to:<br />

1/ Investigate whether these inhibitors are capable of alleviating or preventing the transcriptomic reprogramming;<br />

2/ Assess their analgesic effects in the Spinal Nerve Ligation chronic pain model in rodents and thus their potential as drugs for<br />

transcription therapy.<br />

Materials and Methods: The drug used in our study is RG108, a non-nucleoside DNA-methyltransferase inhibitor. We<br />

administered RG108 to Brown Norway rats via an intrathecal catheter. The Brown Norway rats then underwent spinal nerve<br />

ligation. It consists of tying the L5 nerve close to the dorsal root ganglion and then cutting the nerve distal to the ligature.<br />

Subsequently we assessed the development of allodynia by behavioral testing touching the rat's hind paw with filaments of<br />

different stiffness. The L4 and L5 dorsal root ganglions were harvested at different time points. DNA and RNA were extracted<br />

and methylation and gene expression analysis performed by sequencing technologies.<br />

Results/Conclusions: The work performed by Jana Klukas will not be completed for several more months, so no conclusions<br />

can be drawn at the time of writing.<br />

Note: Jana Klukas received funding for her <strong>BMEP</strong> time in the U.S. from the Mayo Foundation and DAAD.


MIKHAIL LISKOVYKH<br />

Email: liskovykh@mail.ru or michael_liskovykh@hotmail.com<br />

Home Institution:<br />

Institute of Cytology, Russian <strong>Academy</strong> of Sciences, Saint-Petersburg, Russia<br />

Host Institution:<br />

Lab. Molecular Biology of Peptide Hormones, Max-Delbrueck-Center for Molecular<br />

Medicine, Berlin-Buch, Germany<br />

Research Mentors:<br />

Natalia Alenina, Ph.D. & Professor Michael Bader, M.D.<br />

Personal Reaction to the German Experience:<br />

Work and life are highly organized in German laboratories, even in the kitchen. There is free access to all facilities 24 hrs per<br />

day, and a very good atmosphere for non-stop work. Also, it was surprising to me that technicians start very early (6.00-7.00<br />

a.m.).<br />

Greatest Difficulties Encountered:<br />

There were no difficulties during my staying at MDC.<br />

Most Humorous Incident:<br />

One of my colleagues said that the best results were derived from a dish forgotten in the incubator for several weeks. J<br />

In one visit to S2-lab, a friend introduced me to his colleague this way: “This is a strange guy from Russia. He comes here from<br />

time to time, and works with cells, but nobody knows what he’s doing.”<br />

Helpful Hints for Future Students:<br />

I would strongly recommend paying attention to the safety instructions in the laboratory and on the waste sorting system…<br />

Dr. Sturm & Professors Burchardt and Stolte, Students’ conference


Abstract on Research – Mikhail Liskovykh, Ph.D. Student, Institute of Cytology Ras, St.<br />

Petersburg, Russia<br />

Titles: Gene Targeting in Rat iPS Cells and Application of Embryonic Stem Cells for Therapeutic Strategies<br />

Author: Mikhail Liskovykh<br />

Institution: Laboratory of Molecular Biology of Peptides Hormones, Max Delbrueck Center for Molecular Medicine (MDC),<br />

Berlin-Bch, Germany<br />

Project I. Gene Targeting in Rat iPS Cells<br />

The rat is important and superior to the mouse for studying diseases. However, the technology for loss-of-gene-function studies<br />

using rat embryonic stem (ES) cells is not yet well established. Therefore rat induced pluripotent stem (iPS) cells may provide a<br />

notable alternative to ES cells, allowing gene functions in this valuable animal model to be studied. During previous work I<br />

generated several rat iPS cell lines [1]. The aim of the current project was to evaluate if these cells are permissive for the<br />

homologous recombination and thus suitable for the gene targeting and generation of knockout rat.<br />

For the first gene targeting experiment we chose the hypoxanthine phosphoribosyltransferase (HPRT) gene, due to the<br />

existence of a well established system for selecting HPRT-deficient cells [2]. To this end 7x10 6 cell of 2 riPS clones (H5 and<br />

G3, [1]) were electroporated with 30 µg of linearised HPRT-targeting vector. This vector contains a Neo neomycin–resistance<br />

gene (Neo) that results in G418-resistance of transfected cells. Moreover, deficiency in HPRT gene makes cells resistant to 6thioguanine<br />

(6-TG). This molecule cannot be metabolized in HPRT-deficient cells and, therefore, does not exhibit its toxic<br />

effect. After electroporation cells were split on 4x10cm cell culture dishes and selected on G418 or 6-TG-containing media for<br />

2 weeks. Then, clones were picked individually, amplified and analyzed by genomic-PCR analysis. I analyzed 340 clones after<br />

G418 and 24 clones after 6-TG selection (Fig. 1 [364 clones in total]). Unfortunately, all 364 analyzed clones had unaltered<br />

HPRT gene structure, without homologous recombination (Fig. 2). Surprisingly, these cells survived in media, containing 6-<br />

TG. Obviously, the HPRT gene function was invalidated in these clones, but not as a result of homologous recombination.<br />

Project II. Application of Embryonic Stem Cells for Therapeutic Strategies<br />

Since the 1980s, ES cells have been studied and discussed as a remedy for fatal diseases and a route to eternal life, but their<br />

therapeutic use is problematic. One core problem is tumorigenic potential. To overcome this, we previously generated a<br />

transgenic cassette p2A2Btk-TKiresPuro [1]. It can be stably delivered to the genome of ES and iPS cells and is able to drive<br />

expression of TKiresPuro transgene exclusively in pluripotent cells, due to the specificity of 2A2Btk enhancer/promoter<br />

moiety. The cassette TKiresPuro allows both positive (due to the puromycin resistance gene, Puro) and negative (due to the<br />

herpes virus thymidine kinase [TK] gene, making cells sensitive to ganciclovir selection. Thus, we can solve the tumorigenicity<br />

problem by eliminating residual (potentially tumorigenic) pluripotent cells in vitro or in vivo. Such residual pluripotent cells are<br />

present in cell culture even after long-term differentiation protocols. This suicidal approach may facilitate therapeutic cell use.<br />

The aim of this project was to combine this strategy with treatment of pancreatic dysfunction, a cause of diabetes mellitus<br />

affecting a huge population nowadays. The overall strategy which we are currently developing includes 3 steps:<br />

• Differentiation of mouse ES cells into pancreatic precursor cells.<br />

• Engrafting of predifferentiated cells into the pancreas of diabetic mice, with further treatment of experimental animals<br />

with (-)indolactam V-substance, promoting differentiation of pancreatic precursor cells to functional beta-cells.<br />

• Treatment of animals with gancilovir to eliminate undifferentiated, potentially tumorogenic cells.<br />

During the reported period I could set up the conditions for in vitro differentiation of ES cells into definitive endoderm. The<br />

starting protocol was a method described by Melton’s lab [3]. Investigation of 4 different culture conditions revealed that<br />

cultivation of ES cells for 6 days in Advanced-RPMI medium containing 0,5mg/ml BSA, 100 U/ml penicillin, 100 mg/ml<br />

streptomycin, 2 mM L-glutamine, 100ng/ml ActivinA, when additional 4 days cultivation in Advanced-RPMI medium<br />

containing 1x B27 supplement, 100 U/ml penicillin, 100 mg/ml streptomycin, 2 mM L-glutamine, 330nM (-)indolactam V<br />

induces expression of key transcription factors, involved in early steps of pancreatic differentiation. Precursor cells, obtained<br />

under condition N3 were transplanted into the pancreas of nude mice treated with streptozocin (inducing damage of pancreatic<br />

beta-cells). Treatment with indolactam V and ganciclovir is ongoing. To monitor progression of diabetes blood glucose levels,<br />

animals are measured every 3 days. After the experiment they will be examined for presence of tumors and improvement of<br />

metabolic parameters. Homing of engrafted cells into pancreas will be examined by PCR and by histological methods. I believe<br />

this combination of suicidal strategy and in vivo differentiation will have a great potential for later clinical application.<br />

Note: Mikhail Liskovykh was supported by IALS/B.Braun Melsungen-Foundation


KURT MICHAEL REICHERMEIER<br />

Email: kurt-reichermeier@gmx.de<br />

Home Institution:<br />

Justus-Liebig-Universität Giessen<br />

Host Institution:<br />

California Institute of Technology, Howard Hughes Medical Institute, Pasadena, CA<br />

Research Mentors:<br />

Raymond J. Deshaies, PhD, Professor of Biology; Willem den Besten, PhD<br />

Personal Reaction to the U.S. Experience:<br />

First, I was overwhelmed by how much space this country has for streets, freeways and buildings. Everything just seems<br />

bigger, taller and further away. In this highly consumer-oriented country you find unbelievably friendly service everywhere, as<br />

well as the weirdest commercials on the planet. Most of the time you encounter a big smile and a friendly greeting, and it’s up<br />

to you to distinguish between superficiality and honesty.<br />

As a sports fan, I felt like I was in paradise and I immediately picked up a new one, surfing! California is a melting pot of<br />

different ethnicities and cultures which offers a broad range of social and culinary interactions. Overall, the United States offers<br />

you many possibilities to develop your own ideas and is a place where effort will be honestly rewarded. If you can get along<br />

with the different attitudes and mind-sets, it is a great place to live, to do a residency, or a Ph.D.<br />

Greatest Difficulties Encountered:<br />

Getting the documents for the visa together was certainly the greatest pain in the neck. Starting early and being persistent as<br />

well as autonomous pays off!<br />

Most Humorous Incident:<br />

Best of: 1) Mistaking a dolphin for a shark during my first time surfing.<br />

2) A PI almost calling an emergency because one of my kind colleagues dropped an entire bottle of BME.<br />

3) Falling asleep after a night with the Pasadena Crew and missing the flight to NYC the next morning.<br />

Helpful Hints for Future Students:<br />

Be motivated for an academic year, work hard, and have fun! Being ambitious and dedicated will be rewarded, and your PI will<br />

be fine with a few days for traveling or more!


Abstract on Research Topic – Kurt Michael Reichermeier<br />

Title: The Role of the p97-ATPase and Its Adapter Protein UBXD7 in Ubiquitylation and Proteolysis of HIF-1a<br />

Author: Kurt Michael Reichermeier<br />

Institution: Deshaies Lab, Division of Biology, California Institute of Technology, Pasadena, CA<br />

Introduction:<br />

The turnover of proteins is one of the main regulatory mechanisms in cellular organisms and is involved in almost all cellular<br />

processes. The major mechanism to specifically degrade proteins is the Ubiquitin-Proteasome-System (UPS). In order to be<br />

degraded by the UPS, proteins must be conjugated to the protein ubiquitin. Once poly-ubiquitylated, these proteins are<br />

recognized by the 26S proteasome, which facilitates degradation by hydrolysis of ATP. The process of ubiquitylation is carried<br />

out through a three-step reaction by an ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2) and a ubiquitin<br />

ligase (E3). Substrate specificity is determined primarily by the E3. The AAA-ATPase p97, widely considered as ubiquitinspecific<br />

chaperone or segregase, is required for proper ubiquitylation and degradation of particular substrates. The cullin2-<br />

RING-E3-ligase complex targets the Hypoxia-Inducible-Factor-1-alpha (HIF-1α) for ubiquitylation and mediates its<br />

proteasomal degradation. The p97 adapter protein UBXD7 specifically binds the active form of cullin-RING-ligases (CRLs)<br />

and therefore connects the p97-pathway to CRLs. To further investigate the role of p97 and its adapter protein UBXD7 in<br />

ubiquitylation and proteolysis we studied the turnover of HIF-1α in vivo.<br />

Materials and Methods:<br />

We used human cell lines stably transfected with inducible shRNAs and stabilized HIF-1α by treatment of different chemical<br />

reagents. To study the HIF-1α turnover in vivo we developed a cycloheximide time course assay to follow HIF-1α<br />

ubiquitylation and degradation.<br />

Results and Conclusions:<br />

UBXD7 and p97 deficient cells show faster HIF-1α degradation and altered HIF-1α ubiquitylation. Taken together our results<br />

imply that UBXD7 and p97 are necessary for either CRL regulation or proper substrate ubiquitylation or both.<br />

Note: Kurt Michael Reichermeier received funding for his <strong>BMEP</strong> time in the U.S. from DAAD.<br />

Professor Rich, Chairman IALS Board, and Professor Hyun, Associate Provost, UMass Boston


ROBERT RUEMMLER<br />

Email: robbiruemmler@web.de<br />

Home Institution: Institut fuer molekulare Kardiologie, Johannes Gutenberg<br />

Universitaet, Mainz<br />

Host Institution: Department of Pathology, University of Michigan, Ann Arbor, MI<br />

Research Mentors: Peter A. Ward, M.D. (principal investigator); Markus Bosmann,<br />

M.D. (supervisor, post-doc)<br />

Personal Reaction to the U.S. Experience:<br />

This basically being my first time in the U.S., it has been a great experience. The different way of working (and budgeting)<br />

compared to Germany made it possible for me to work more independently and on a higher scientific level. Seeing the<br />

differences and similarities in society and culture on my own and for a longer period of time was totally worth it.<br />

Greatest Difficulties Encountered:<br />

Although Germans have the advantage of getting their driver’s licenses without any kind of test, buying, registering, and<br />

maintaining your own car can get extremely annoying and expensive. Be aware of insurance requirements, etc., and figure out<br />

if you really need your own ride before you decide to go for it.<br />

Most Humorous Incident:<br />

Way too many. Every stereotype holds a grain of truth, as I found out one right at the beginning of my stay: When I was<br />

signing my apartment lease, my landlord asked me where exactly I was from. After I told him ‘near Frankfurt’ he first tried to<br />

pin Prince William’s royal wedding on Germany, and then, after I had told him that they are British, asked me how far away<br />

that was and if we spoke with the same accent!<br />

Helpful Hints for Future Students:<br />

Take the time to look for an apartment, especially if you’re moving to smaller student cities. Look on craigslist, go through the<br />

torture of Skype interviews, and move in with a bunch of other people. There’s just no better way to find contact. People are<br />

more open than in Germany, but often on a more superficial level, so it might be harder to actually make friends at work.<br />

Enjoy!


Abstract on Research Topic – Robert Ruemmler<br />

Title: Extracellular Histones promote Complement-induced Acute Lung Injury<br />

Authors: Robert Ruemmler, Markus Bosmann, Norman F. Russkamp, Bethany B. Moore, Marc Monestier, Firas S. Zetoune, J.<br />

Vidya Sarma, Peter A. Ward<br />

Institution: Department of Pathology, University of Michigan, Ann Arbor, MI<br />

Introduction:<br />

Acute lung injury (ALI/ARDS) is a major perpetrator or morbidity and confronting clinicians with non-availability of specific<br />

treatments. We investigated the implications of the complement activation fragment C5a by establishing a model of C5ainduced<br />

ALI in mice. Lung injury in C5a-ALI was dependent on PMNs, Akt-MEK1/2 signaling and required both C5a<br />

receptors, C5aR and C5L2. Furthermore, C5a-ALI was accompanied by the generation of extracellular histones. Neutralization<br />

of histone H4 with antibodies reduced the severity of alveolar permeability disturbances and silenced the production of<br />

inflammatory mediators. Treatment of lung epithelial cells with purified histones provoked rapid cell death. Administration of<br />

histones to the airways of rodents severely compromised inter-alveolar gas exchange, respiratory functions, alveolar<br />

permeability and initiated an inflammatory response including pulmonary consolidation visualized by MRI. These studies<br />

describe histones as novel mediators of complement induced tissue injury. Neutralization of extracellular histones may emerge<br />

as a beneficial treatment during ALI.<br />

Materials and Methods:<br />

The main method used for this project was the in vivo ALI model in mice and rats. Briefly described, animals were<br />

anesthetized with a ketamine/xylozine solution. Afterwards a vertical midline incision right on top of the thyroid gland was<br />

made. The gland lobes were severed and the trachea was laid bare. The substances to trigger immune response (C5a, Histones,<br />

LPS) were injected directly into the trachea. After 8 hours the animals were euthanized and the lungs were flushed with PBS.<br />

Those bronchoalveolar lavages (BALs) were collected and used for neutrophil counting and determining albumin leakage via<br />

ELISA. Histone concentrations were assessed with Western Blots. Further methods were cell survival studies with murine lung<br />

epithelial cells after incubation with histones. LDH release was determined after incubating the cells for 1 hour.<br />

Results/ Conclusions:<br />

Our results indicate that extracellular histones are a crucial component of complement-mediated inflammatory processes. We<br />

were able to detect largely increased concentrations of extracellular histones after C5a ALI. Furthermore, the application of<br />

histones into the airway lead to severe respiratory distress and gas exchange impairment. Cell culture studies showed that<br />

histones are highly cytotoxic and caused immediate cell death. C5a receptor deficient mice were partly protected from the in<br />

vivo effects. Additionally, treatment with neutralizing histone antibodies had protective effects as well. We conclude that<br />

extracellular histones might be a valuable target for the treatment of ARDS and sepsis in the future.<br />

Note: Robert Ruemmler received funding for his <strong>BMEP</strong> time in the U.S. from the Boehringer Ingelheim Fond.


CHRISTIAN SCHMIDT-LAUBER<br />

Email:<br />

Christian.schmidt-lauber@uni-muenster.de<br />

Home Institution:<br />

Westfälische Wilhelms-Universität Münster<br />

Host Institution:<br />

Division of Rheumatology, University of Massachusetts Medical School<br />

Worcester, MA<br />

Research Mentor:<br />

Ann Marshak-Rothstein, Ph.D., Professor of Medicine<br />

Personal Reaction to the U.S. Experience:<br />

I had an amazing time during my <strong>BMEP</strong> stay. Personally and scientifically I have had great experiences and probably never<br />

learned as much within such a short time. For a long time it had been a dream of mine to spend a certain time of my studies in<br />

the U.S., not only because of its outstanding academic opportunities and reputation, but also because of its cultural diversity.<br />

Today I can say that I found both during my <strong>BMEP</strong> time. I made good friends and definitely enjoyed the presence of people<br />

from so many countries and cultures. Also, I am very happy to have had the opportunity to take part in the research, as well as<br />

clinical teaching, at UMass. The opportunities in both fields highly impressed me.<br />

Greatest Difficulties Encountered:<br />

Getting around! Concerning the living expenses it is certainly a plus not to live in one of the big American cities. However,<br />

getting around is more difficult. Be prepared that you might have to get a car.<br />

Before starting to work with animals you have to complete a lot of forms and tests, so that it may take a while before you are all<br />

set to start. Take that time to get settled down, travel around, gain some clinical experience or start in vitro experiments.<br />

Most Humorous Incident:<br />

There were a lot of funny incidents but having an all-American Thanksgiving with a friend’s family was definitely the best one.<br />

Helpful Hints for Future Students:<br />

• Be careful when looking for a room/car or whatever on craigslist!<br />

• Asking the people around you is always the easiest way to get information. Thus: ask, ask, ask!<br />

• If planning to buy a car, requesting a driving record from the “Kraftfahrt Bundesamt” before your departure from<br />

Germany can lower your insurance fees.<br />

• Get an American debit card (usually without any fees) and cell phone.


Abstract of one Research Topic – Christian Schmidt-Lauber<br />

Title: Gadolinium and Gadolinium based contrast agents activate the Nalp3 inflammasome<br />

Authors: C. Schmidt-Lauber 1 , L. Bossaller 1 , H. Abujudeh 2 , E. Gravallese 1 , J. Kay 1 , and A. Marshak-Rothstein 1<br />

1 Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA<br />

2 Department of Radiology, Massachusetts General Hospital, Boston, MA<br />

Introduction:<br />

Nephrogenic systemic fibrosis (NSF) is a rare but crucial fibrosing disorder that develops in renal insufficient patients after<br />

exposure to Gadolinium based MRI contrast agents (GBCA). NSF generally presents with dermal hyperpigmentation,<br />

induration and fibrosis accompanied by joint contractures but can also affect other organs. The mortality is significantly<br />

increased in NSF patients. To date, the mechanism of GBCA-induced fibrosis is incompletely understood. However, it is<br />

believed that Gadolinium may precipitate to exert fibrotic effects. Other metals and crystals are already known to activate<br />

inflammasomes. This study aims to elucidate the effects of Gadolinium on different types of macrophages.<br />

Materials and Methods:<br />

Bone marrow derived macrophages (BMDM) were isolated from B6, Asc -/- and Nalp3 -/- mice. If indicated BMDM were<br />

primed to M1 and M2 macrophages with IFNg or IL4, respectively. After subsequent priming with LPS cells were stimulated<br />

with different Gadolinium (Gd) containing agents and IL1 beta secretion and cleavage as well as Caspase1 activation were<br />

detected by ELISA and WB. Additionally, Gd-DTPA was injected i.p. in B6 and Asc -/- mice and FACS analysis of the<br />

peritoneal washout was performed.<br />

Results:<br />

Omniscan, Gd-DTPA as well as Gd-Cl induce a Nalp3 and Asc dependent Caspase1 and IL1 beta activation in isolated primary<br />

BMDM. For all three compounds this effect was concentration dependent. The same effects were seen when BMDM were<br />

differentiated to M2 macrophages but not in M1 macrophages. A reduction of IL1 beta cleavage in M1 macrophages was also<br />

seen for other inflammasome activators. I.p. injection of Gd-DTPA led to an influx of granulocytes and inflammatory<br />

monocytes that was not seen in Asc -/- mice. These results show that Gadolinium containing agents activate the Nalp3<br />

inflammasome and might help to further elucidate the pathogenesis of NSF.<br />

Acknowledgments: The help of Vijay Rathinam and Peter Düwell is highly acknowledged.<br />

Christian Schmidt-Lauber received funding for his <strong>BMEP</strong> time in the U.S. from DAAD.<br />

Faculty members, Students’ conference, Boston <strong>2012</strong>


LINDA SCHROEDER<br />

E-Mail: lima.schroeder@yahoo.de<br />

Home Institution: RWTH Aachen<br />

Host Institutions:<br />

Maastricht University, Maastricht, NL<br />

Manipal University in Manipal, India<br />

Personal Reactions:<br />

Since I did a master's program in the Netherlands my experiences will differ from those of the other participants. The master's<br />

program in Global Health is a one-year program in English, linking health and healthcare with economic development, politics<br />

and the socio-cultural environment. The desire to understand health problems in a global context and to learn about strategies in<br />

order to tackle them made me participate in this program in addition to my medical education. Working with fellow students<br />

from different countries and various educational backgrounds, I saw medical issues from a different point of view. A special<br />

learning experience was the online sharing of courses and seminars with students from partner universities in India and Canada.<br />

With a group of students from Manipal University in India we worked online on the same assignment, but since we had never<br />

met each other personally this was a special challenge. In the second semester we got the opportunity to choose an elective<br />

track at one of our partner universities. I decided to take the track “Global Health in Developing Countries” in India because I<br />

was curious to live and study in that country, with its different culture and way of living, and to learn about its healthcare<br />

system which is so different from the one I knew. Here I finally met the fellow students I had worked with online during the<br />

last four months. In India I attended classes about the Indian health system and the health challenges this country is facing. The<br />

most interesting part, however, was the field work. I had the chance to go to several primary health centers, the rural healthcare<br />

facilities providing the basic units of India´s health care. In contrast to that, I got to know the Kasturba Hospital in Manipal,<br />

which ranks among the best hospitals in the country. During the Pulse Polio Day I experienced how a vaccination campaign<br />

across the whole country works. Taking part in this program was a very rich experience and will accompany and support me in<br />

my future work as a doctor.<br />

Greatest Difficulties Encountered:<br />

The structure and organization I experienced in the Netherlands were similar to my education in Germany and due to the fact<br />

that the classes were in English I did not have too many difficulties during my time in Maastricht. This was different in India.<br />

Here I sometimes got a phone call saying that the schedule was changing and the lecture was starting in a few minutes.<br />

Most Humorous Incident:<br />

For foreigners it is always difficult to understand what an Indian means when he shakes his head. You really must be able to<br />

differ very exactly whether it means “yes” or “no”. Otherwise this leads to funny misunderstandings. My Indian friends could<br />

not really understand my confusion.


Abstract on Research Topic – Linda Schroeder<br />

Title: Mental health and social networks of older persons in Karnataka, India<br />

Author: Linda Schroeder, M.Sc. Global Health<br />

Institution: Department of Public Health, Manipal University, Manipal, Karnataka, India<br />

Introduction:<br />

Aging of the population is a global phenomenon that is both inevitable and predictable. It will change society at many levels<br />

and in complex ways. Due to the immense impact the aging of the population will have globally, the WHO selected aging and<br />

health as the topic of the World Health Day in <strong>2012</strong>. India´s aging population is growing fast. Due to declining birth, death and<br />

infant mortality rates coupled with an increase in life expectancy, the number of persons older than 60 years in the population is<br />

expected to increase. Traditionally, people in India live in joint families, a family structure including multiple generations, so<br />

that older persons continue to live in their own homes embedded in the social structures of the family, the neighborhood and the<br />

community, which provides various opportunities for companionship and social life. But rapid urbanization and societal<br />

modernization have brought a change in family values and the framework of family support, leading to increasing numbers of<br />

older persons living in old people’s homes. Living away from the family and a familiar community might influence the mental<br />

health of the elderly.<br />

Materials and Methods:<br />

The study aims to examine the mental health status of the older persons in relation to their social networks. Therefore two<br />

groups were composed and older persons living either in an old people’s home or in the community were interviewed. A<br />

pretested questionnaire was designed to gather information about the socioeconomic background, the social support the elderly<br />

perceive and their emotional health. The collected data were analyzed using the Statistical Package for Social Sciences.<br />

Comparing the results from both groups will provide information about the mental health status of the individuals and the social<br />

support the older persons perceive.<br />

Results/Conclusions:<br />

The aging of the population is a global phenomenon that is now occurring much faster in low and middle-income countries.<br />

One example is India, with its changing demographic and social structures leading to a growing number of older persons living<br />

alone. As the majority of them had never conceived that they would be spending their autumn years away from their family, the<br />

full implications of this change have yet to be played out. Facing this urgent issue the government of India, as well as nongovernmental<br />

organizations, are developing strategies to deal with the complex issue of the aging population, which is expected<br />

to more than double to 173 million during the next two decades.<br />

Note:<br />

Linda Schroeder received funding for her <strong>BMEP</strong> time in Maastricht in <strong>2011</strong>/<strong>2012</strong> by IALS/B.Braun Melsungen-Foundation..


ANNA SIEBEN<br />

Email: a.sieben1@gmx.de<br />

Home Institution: Rheinisch-Westfälische Technische Hochschule Aachen<br />

Host Institution: University of California, Los Angeles, CA<br />

Research Mentor: Baljit S. Khakh PhD, Associate Professor, Department of Physiology,<br />

UCLA<br />

Personal Reaction to the U.S. Experience:<br />

When I arrived in the U.S. after a 24-hour trip, I was completely overwhelmed by all the new impressions. It was full of colors,<br />

lights and advertisement signs. The highway had six lanes and everything was much bigger than in Germany (even the<br />

butterflies). The people in my lab gave me a warm welcome, and I really enjoyed working in this multicultural and nice<br />

atmosphere. With the help, patience, and support of my new colleagues I easily found access to my research project. I am really<br />

grateful to have had the chance to experience research in the U.S. In my dorm I met a lot of young people from all over the<br />

world. It was great to learn about their lives and cultures, and for all their differences to find a lot of things we have in common.<br />

Greatest Difficulties Encountered:<br />

Not having a car in Los Angeles, I was severely restricted in getting around. Public transportation is really bad and at times I<br />

had to wait one hour for the next bus. In addition, it was hard for me to get used to the production of these big amounts of<br />

garbage. Everywhere I ate I got my food and drinks on plastic plates and in plastic cups.<br />

Most Humorous Incident:<br />

The most humorous incidents happened when my roommates (both native speakers) and I were having conversations.<br />

Sometimes there were really funny misunderstandings when I tried to pronounce a word in English and both of them<br />

understood something completely different because of my German accent.<br />

Helpful Hints for Future Students:<br />

ñ Try to find accommodation in a dorm or shared apartment to get directly into contact with people outside the lab.<br />

ñ You should load Skype onto your computer J<br />

Faculty members, Students’ conference, Boston <strong>2012</strong>


Abstract on Research Topic – Anna Sieben<br />

Title: TRPA1 channel mediated spotty calcium signals in astrocytes: impact of oxidative stress and store depletion<br />

Authors: Anna Sieben, Baljit S. Khakh, Ph.D.<br />

Institution: Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA<br />

Introduction:<br />

Astrocytes are the predominant glial cell type within the central nervous system. It has been shown that they can modulate<br />

neuronal transmission and activity by the release of “gliotransmitters” which are neuroactive molecules released due to a<br />

change in astrocytic calcium concentration ([Ca 2+ ]i). Thus, the elevation of [Ca 2+ ]i is widely considered a form of glial<br />

excitability (Agulhon et al., 2008). Recently, it has been shown that Ca 2+ fluxes through TRPA1 channels, a member of the<br />

transient receptor potential (TRP) channel family, significantly contribute to astrocyte resting Ca 2+ levels. These TRPA1mediated<br />

Ca 2+ fluxes are highly localized near the plasma membrane and are of “spotty” microdomain nature (Shigetomi et al.,<br />

<strong>2011</strong>) .<br />

The aim of this work was to find out more about the nature of these spotty calcium signals. Therefore, we focused on the<br />

activation mechanism of TRPA1 channels in astrocytes. We tested the impact of depletion of intracellular calcium stores and of<br />

the induction of oxidative stress on the activation of TRPA1 channels.<br />

Materials and Methods:<br />

We used hippocampal astrocyte-neuron co-cultures from one day old rat pups and conducted epifluorescence microscopy, using<br />

approaches to measure both global and near-membrane Ca 2+ signals. To report near plasma membrane Ca 2+ signals, astrocytes<br />

were transfected with the genetically encoded calcium indicator Lck-GCaMP5 which is tethered to the membrane by the Nterminal<br />

domain of Lck, a Src tyrosine kinase (Shigetomi et al., 2010). To measure changes in the global [Ca 2+ ], astrocytes<br />

were loaded with the organic calcium indicator dye Fluo-4/AM. We used a standard store depletion protocol employing 10 µM<br />

cyclopiazonic acid (CPA), a specific inhibitor of Ca 2+ -ATPase, to test the effect of store depletion on the activation of TRPA1.<br />

By applying 1 mM hydrogen peroxide (H2O2) to astrocytes we induced oxidative stress and therefore could test its impact on<br />

TRPA1 activation.<br />

Results/ Conclusions:<br />

We found that store depletion induced an increase in both spotty signals or global [Ca 2+ ]. After application of hydrogen<br />

peroxide we detected an increase in the number of spotty Ca 2+ signals. The store depletion and hydrogen peroxide induced<br />

elevations in Ca 2+ fluxes were reduced by blocking the TRPA1 channel with its specific antagonist HC 030031 (40 µM). We<br />

conclude that TRPA1 channels in astrocytes are opened by intracellular Ca 2+ store depletion and by oxidative stress.<br />

References<br />

Agulhon et al. (2008). Neuron, 59:932-946.<br />

Shigetomi et al. (<strong>2011</strong>). Nature Neuroscience, 15(1):70-80.<br />

Shigetomi et al. (2010). Nature Neuroscience, 13(6):759-766.<br />

Note: Anna Sieben received funding for her <strong>BMEP</strong> time in the U.S. from the DAAD.


Friends of <strong>BMEP</strong> and IALS – Financial Support since 1985<br />

The <strong>International</strong> <strong>Academy</strong> of Life Sciences (IALS) and its subsidiary, the Biomedical Sciences Exchange Program (<strong>BMEP</strong>),<br />

wish to express sincere gratitude to the individuals and organizations listed below who have contributed to the FRIENDS OF<br />

IALS since the 1985 appeal for financial support.<br />

Benefactors – up to 5000 Euros<br />

• Dr. Michaela Banck and Dr. Andreas Beutler, Mayo Clinic, Rochester, MN<br />

• Prof. Claudia Barth, Köln<br />

• Dr. Dennis Dey, MIR Neurology & Spine Center, Cumberland, MD<br />

• Brita Dole, Bad Oeynhausen<br />

• Dr. Karsten Dreinhöfer, Ulm<br />

• Dr. Heinrich Hagehülsmann & Ute Hagehülsmann, M.A., M.Sc., Rastede<br />

• Sabine Hermann, DMD, Löhne<br />

• Prof. Roland Hetzer, Berlin<br />

• Dr. Holger Kranich, Gila River Health Care Corporation, Phoenix,AZ<br />

• Fr. Vöth Naber & PD Klaus Naber, Murnau<br />

• Drs. Marion Schaeffer & Jürgen Schaeffer, Hannover<br />

Patrons – up to 1000 Euros<br />

ñ Dr. Dr. Elmar Burchhardt, Cambridge, Massachusetts<br />

ñ Dr. William Deal, Dean em., Birmingham, Birmingham, AL<br />

ñ Prof. Torsten Doenst, Freiburg<br />

• Prof. Harald Jüppner, Harvard Medical School, Boston, MA<br />

• Dr. Frank-Dieter Loitz, Braunschweig<br />

• Dr. Christian Schäffer, Stuttgart<br />

• Prof. Hans-Joachim Schurek, Lingen-Ems<br />

Sponsors – up to 500 Euros<br />

• Dr. Berend-Tüge Berendsen, Mönkeberg<br />

• Heiko Flügel, M. Sc., Bad Soden<br />

• Dr. Jan Hilpert, Berlin<br />

Prof. K.W. Kuehn, Karlsruhe<br />

• Prof. Klaus-Hinrich Neumann, Magdeburg<br />

• Dr. W. Scott Long, Connecticut Hospice, New Haven, CT<br />

• Prof. Klaus-Hinrich Neumann, Magdeburg<br />

• Dr. Karin Maass-Poppenhusen, Kiel<br />

Sustainers – up to 250 Euros<br />

ñ Dr. Anne Dörte Achtert, Berlin<br />

ñ Dr. Stefan Blaas, Regensburg<br />

ñ Dr. Judith Brandstätter, München<br />

ñ PD Dr. Giuliano Ciarimboli, Münster<br />

ñ Prof. Thomas Deller, Kronberg<br />

ñ Dr. Eva Handke, Hamburg<br />

ñ Dr. Irmtrud Jäckle-Meyer, Göttingen<br />

ñ Dr. Volkmar Lufft, Rendsburg<br />

ñ Dr. Rüdiger L. Prosst, Fellbach<br />

ñ Prof. Jörg Rademacher, Minden<br />

ñ Dr. Benjamin Schäfer, Bangor, Maine<br />

ñ Dr. Burkhard Schulte, Friesoythe


Donors – up to 100 Euros<br />

• Dr. Jan Boublick, New York<br />

• Prof. Jürgen & Barbara Floege, Aachen<br />

• Dr. Karl Fryburg, Tucson, AZ<br />

• Dr. Dirk Hentschel, Harvard Medical School, Boston, MA<br />

• Dr. Anne Hofer, Tübingen<br />

• Dr. Robert Massey, Dean em, University of Connecticut, Farmington, CT<br />

• Dr. Johannes Richter, Göttingen<br />

• Dr. Felix Wedegärtner, Hannover<br />

Corporate Sponsors & Foundations – up to 25,000 Euros<br />

• Bayer Crop. Sciences, Monheim<br />

• Boylan Foundation, Rhinebeck, NY<br />

• B. Braun – Melsungen AG, Melsungen<br />

• Genzyme Corporation, Framingham, MA<br />

• S. Karger Publishers, Basel<br />

• Provena Covenant Medical Center, Urbana, IL<br />

• Boehringer Ingelheim Inc., Ridgefield, CT<br />

• Preussag AG, Hannover<br />

• Carl Duisburg Foundation, Hannover<br />

Founding institutions:<br />

Mount Desert Island Biological Laboratory<br />

Medizinische Hochschule Hannover


Who's Who in IALS<br />

Officers<br />

Hilmar Stolte, MD, PhD<br />

Univ. Professor emeritus<br />

Medizinische Hochschule Hannover<br />

President, <strong>BMEP</strong> & IALS<br />

Hannover & Potsdam, Germany<br />

Benjamin Schäfer, MD<br />

Northeast Cardiology Associates<br />

Treasurer, <strong>BMEP</strong> USA, Inc.<br />

Bangor, ME, USA<br />

Raymond L. Williams, JD<br />

Roy, Beardsley, Williams and Granger, LLC<br />

Clerk, <strong>BMEP</strong> USA, Inc.<br />

Ellsworth, ME, USA<br />

Administrative Offices<br />

European Office<br />

IALS / <strong>BMEP</strong><br />

Prof. Hilmar Stolte, MD<br />

Medizinische Hochschule<br />

Hannover<br />

Carl-Neuberg-Str. 1<br />

D-30625 Hannover<br />

T +49 511 532 6662<br />

F +49 511 532 6663<br />

ials@lifesciences.net<br />

European Office<br />

IALS / <strong>BMEP</strong><br />

Heidrun Stache<br />

IALS<br />

Kaiserstr. 15<br />

D-32545 Bad Oeynhausen<br />

Germany<br />

T +49 5731 23941<br />

F +49 5731 23942<br />

stache@lifesciences.net<br />

Klaus Neumann, MD<br />

Vice President IALS (Europe)<br />

Professor of Medicine<br />

Magdeburg, Germany<br />

Robert Rich, PhD<br />

Chairman of the Board, IALS<br />

Professor of Law & Political Sciences<br />

University of Illinois, Urbana, IL, USA<br />

Michael Wiederholt, MD<br />

Univ. Professor emeritus, Freie Universität Berlin<br />

European Representative & Trustee, <strong>BMEP</strong> Inc.<br />

IALS Office<br />

Brandenburg-Berlin<br />

Svetlana Orlova, PhD<br />

IALS<br />

Am Neuen Markt 6<br />

D-14467 Potsdam<br />

Germany<br />

T +49 331 8170 701<br />

F +49 331 8170 702<br />

davorl@rumbler.ru<br />

N. American Office<br />

<strong>BMEP</strong><br />

Laurie B. Williams<br />

56 Hancock Street<br />

Ellsworth<br />

ME 04605<br />

USA<br />

T +1 207 667 1920<br />

F +1 207 667 5513<br />

bmep@midmaine.com<br />

in public / private partnership:<br />

GBM – Association for Innovation and Technology Transfer in Biomedicine, Ltd, Potsdam – Bad Oeynhausen<br />

GBM@lifesciences.net

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