Yearbook 06-07


Lena Kahlke
Home Institution Christian-Albrechts-Universität zu Kiel Host Institution Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA Research Mentor: Professor Jing X. Kang MD, PhD E-Mail: hawaii2002@gmx.net
Research Topic see Abstract
Personal Reactions to the U.S. Experience You are going to Boston soon? Congratulations!! You have been in the area but didn’t stop by to investigate the city for at least a couple of days? Your loss!! Boston is one of the most fascinating and charming cities I have ever been to. It is small enough to get around by bike easily (as long as YOU take care you don´t get run over!!) but it still offers a great variety of events and activities so you won´t get bored at any time! The biggest problem will probably be to decide what to do first: enjoy the diversity of theatre-, opera-, musical events; investigate Chinatown or the charming Little Italy with its characteristic little restaurants; do whale watching, walk around downtown Boston, visit one of the famous museums, investigate the Harvard territory, go to the beach or enjoy Boston´s enormous nightlife. Once you managed to decide what to do, you will learn how friendly and helpful the “Bostonians” are. It took me only a moment to feel like home. Especially all the foreign students are very eager to make you feel comfortable and I got so much “useful information” in the beginning about where to live, what to do, so that I was totally confused! To sum this up: Boston is a great city! Very European, very charming- a “must-see”! The labwork on the other hand was very special! It is true that Boston with its world famous universities and hospitals creates a scientific environment that attracts researchers from all over the world. Therefore very often people with different cultural backrounds work together. I worked in a laboratory with Chinese only - what was inspiring on the one hand but very challenging on the other! It took me a while to get used to the Asian way of organizing a lab and I remember many funny incidents because of misunderstandings (for example: another German student using the microwave in the meeting room to thaw some samples because our lab manager understood she wanted to warm up her lunch).
Greatest Difficulties Encountered Using my mountain bike to go to work. 1st challenge: not to get run over by truck drivers who are totally surprised to see a person riding a bike! 2nd challenge: not to run over/into one of the holes in the road surface (which are really deep!) - that would probably have led to serious injuries and hospitalization!!!
Most humorous incident ...the German student (I mentioned before) forgot the samples (I mentioned before) in the microwave in the meeting room (I mentioned before). The whole microwave caught fire, the fire alarm went off and the whole building with its 200 labs got evacuated!
Helpful Hints for Future Students Go to the best café ever in the North End: Boston Beanstock with wireless internet access for free and the best café latte of the town:) (www.bostonbeanstock.com) On Thursday night there is a pubtour organized by the Euroclub of the MIT which is worth going! Check: http://euroclub.mit.edu/Activities/pub-tour/ There is a great outlet mall in Wrentham. You better bring your credit card!!! Check www.craigslist.org if you are looking for a room/ a bike/ or almost anything else. Go see at least one Celtics game!!! (I am a big fan!) HAVE FUN!!
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Abstract on Research Topic
The Influence of Increased Omega-3 Fatty Acid tissue levels on Inflammatory Activity in a Mouse Model of Cerulein-induced Acute Pancreatitis (AP) and AP-associated Lung Injury

Author: Lena Kahlke

Institution:
CVRC, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Background:
Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) are precursors for many lipid mediators and play an important role in regulation of inflammation. The n-6 PUFA derived mediators are generally known to promote inflammation, wheras the n-3 PUFA derived mediators are less active and even show antiinflammatory effects. Transgenic fat-1 mice offer an innovative opportunity to gain insight on the impact of the n-3 PUFAs on a variety of inflammatory diseases. Former mice studies in our lab have shown that increased n-3 PUFA tissue levels protected mice from DSS-induced colitis and decreased inflammation in D-GalN/LPS-induced acute hepatitis.

Purpose and Methods:
For the experiments we used the transgenic fat-1 mouse, expressing a C. Elegans desaturase to endogenously form n-3 PUFA from n-6 PUFA. The gaschromatography of different fat-1 mouse organs revealed an outstanding high concentration of n-3 PUFAs in the pancreatic tissue. Following former studies with the transgenic mice the purpose of this study is to investigate the influence of highly increased n-3 PUFA concentration in the pancreas on the inflammatory activity, and quantitate the AP-associated lung injury, representing the systemic reaction due to mediators released in the pancreas. Of special interest are ratios of n-6 derived and n-3 derived mediators and their role in pathways leading to the potential protective effects.

Procedure:
At first we set up the mouse model of cerulein-induced acute pancreatitis (AP) and AP-associated lung injury by trying different amounts of cerulein injections. Having established the effective dose (12 hourly injections of 50ug/kg bodyweight in 200ul saline) the wild type group and the fat-1 group (each consistent of 13 animals) were treated with either 12 hourly injections of cerulein in saline or only saline (control). One hour after the last injection all animals were sacrificed, we collected pancreas, lung and liver samples and draw blood. We started analysing parameters that reflect severity of inflammation and quantify a potential difference in the two groups:

Histology of pancreas and lung tissue (to quantitate severity of inflammation/tissue damage)
Amylase and Lipase
Myeloperoxidase (MPO) in lung and pancreas (as a reflection of neutrophil sequestration within the tissue) and MPO-antibody staining of lung tissue
rtPCR of different pro- and antiinflammatory mediators (IL-6/IL-10/TNF-α/TGF-ß/IL-1ß)
DAPI stains of lung and pancreas tissue (to quantitate apoptosis)
Gaschromatography of pancreatic tissue (to analyse the n-6/n-3 PUFA concentration in the tissue)
IL-6 ELISA of the serum as a general inflammation marker

Further parameters of interest are the NFkB-activity in the pancreas or characterisation of lipid mediators, with special focus on the relative difference between n-6 derived mediators like PGE2, LTB4, LXA4 and their n-3 derived counterparts (RvE1, RvDs, PGE3, LTB5).

Results:
Analysis of the collected data will be performed soon.