Konrad Aden  

Home Institution
Christian Albrechts Universität zu Kiel

Host Institution(s)
Department of GastroenterologyWashington University School of Medicine,St. Louis, Missouri
Research Mentor: Brian Dieckgraefe, M.D., PhD.

E-Mail: konrad.aden@gmx.de
Research Topic
see Abstract
Personal Reactions to the U.S. Experience
Living in the Midwest is like driving a 10 year old VW Golf. It is not a fancy car, as San Francisco or NY might be, but it is a good piece of craftsmanship, and at the end you get a sense of what a car is really about.
St. Louis is an average city with its typical problems of suburban flight, and social and ethnical disparity. It has the “Gateway Arch,” a 192 m high bent piece of steel, and the traces of the Olympic Games and the World’s Fair, both hosted in 1904 in St. Louis, are still detectable. The neighbourhood I lived in used to be the Olympic Village and the college football team of Washington University plays in the former Olympic stadium.
Budweiser, Baseball and its University symbolize the city life, and, once you acknowledge that fact, your life has a very simple and enjoyable pattern. From “Bench to Baseball” was one of my favourite issues in the constant try to unfold the mysteries of both, intestinal immunology and American society!
Working in an ambitious scientific environment is very inspiring, and having your own project to take care of really trains you in self-responsibility and working autonomously. Overall I became aquainted with various techniques. The experience of not having a postdoc in the background, who could easily fix the problems I was struggling with, really trained me in patience and perseverance. Consequently, even if my long-term goal is not in the basic research area, I became familiar with various skills that I can easily transfer to the clinical area.
Greatest Difficulties Encountered
Due to the fact that I had been to the Unites States before, I didn’t expect to encounter any great difficulties. Still, I suffered the well-known symptoms of German food deprivation. After 10 days I released myself from a 14-day schedule of a fast food-based nutrition study, due to heavy physical and psychical side effects!
Most humorous incident
Thousands of miles away from home, I happened to visit my first Octoberfest right in St. Louis, and I guess it was more German than any Octoberfest in Munich has ever been. The priest asked in a bilingual prayer for the blessing on the beer and on the festival, and together we intoned the German and the American national anthems. The brass band came right from “Straubing,” and the entire event was sponsored by the German distillery “Killepitsch”, which seduced me into tasting too many of its wonderful liquors. Sometimes you are looking for something exciting and all you find is “good old home”.
Helpful Hints for Future Students
If you really want to know the country, get enrolled in any kind of volunteering. When working at a top university, you are easily seduced into considering the people around you as the average social class. Volunteering in any kind of underprivileged environment puts your feet back down on the floor and extends your perspective.
Become aware of what you are really expecting from research or clinical work. Look carefully for a lab, which meets your scientific as well as your personal needs. At the end, it’s not the output rate of your lab that makes your individual academic year successful.

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Abstract on Research Topic

Fundamental difference in hemopoietic growth factors (Flt3L, GM-CSF) on experimental mouse colitis and the innate immune response

Authors: Konrad Aden, Satheesh K. Sainathan, Kumar S. Bishnupuri, Quishi Luo

Institution: Washington University, St. Louis, MO

Introduction:
Disordered innate immune clearance may play a major role in the etiology of IBD. Plasmacytoid dendritic cells (pDC) are the major source of type I interferons, which may regulate the mucosal immune response. We previously showed that treatment with GM-CSF dramatically reduces the severity of DSS-colitis in a mechanism involving dendritic cell populations, including the pDC. Flt3 Ligand (Flt3L) is a growth factor that similarly expands dendritic cells (DC) populations.

Aim:
To examine the differential effects of Flt3L and GM-CSF on DSS-induced colitis and the innate immune response.

Method:
Colitis in mice was induced with 5% DSS in their drinking water for 7 days. Mice were administered with Flt3L (20µg/mice) daily and compared to control groups. Disease activity index (DAI), histological analysis and immunohistochemistry was performed. Real Time RT-PCR was used for quantitative analysis of inflammatory genes. Flow cytometry was performed using anti-CD11c(DC), -440c(pDC).

Results:
Flt3L aggravates DSS-induced colitis in mice, by all disease end-point measured. Histopathological analysis showed the trend towards worse inflammation in DSS+Flt3L treated mice compared to the DSS control group. Real Time RT-PCR exhibited a significant induction of the proinflammatory genes like TNFα and IL-1ß, which was worse in Flt3L+DSS treated animals. In order to examine the effects of Flt3L and GM-CSF on interferon production following CpG treatment, mice were pre-treated with GM-CSF, Flt3L or left untreated for 5 days. 4h prior to scarification each group was stimulated with CpG, a TLR9 agonist. Flow cytometry showed similar effects of both, GM-CSF and Flt3L, on dendritic cell populations. Quantitative Real Time RT-PCR analysis of colon and spleen tissue exhibited a drastic increase of type I-IFN gene induction in GM-CSF , but not in Flt3L pre-treated animals following CpG stimulation. A number of other genes were identified that were differentially expressed following GM-CSF or Flt3L treatment, including Cathelicidin, an antimicrobial peptide which is known to play a major part in innate immune defense.

Conclusion:
Flt3L and GM-CSF are hemopoietic growth factors, both capable of increasing pDC population. While GM-CSF ameliorates, Flt3L dramatically aggravates DSS-induced colitis in mice. Our data provide for the first time evidence on the fundamental differences between Flt3L and GM-CSF on TLR-driven innate immune response in experimental mouse colitis.