Lena Krause  

Home Institution
Charité Universitätsmedizin Berlin

Host Institution
Cardiovascular Research Center, Massachusetts
General Hospital, Harvard Medical School
Boston, Massachusetts
Research Mentor: Jing X. Kang, M.D., Ph.D.

E-Mail: l.f.krause@web.de

Research Topic
see Abstract
Personal Reactions to the U.S. Experience
It was a great experience for me, which I wouldn’t want to miss. People were very friendly and open and we made good friends here. In my opinion, the Boston area is a very nice place to visit. Since there are so many colleges and universities in this area, the city is very young and sophisticated. I was impressed by how international everything here is, which comes to an extreme in the scientific field. Estimated, there are about 85 % Asians working in our research building and another 10 % Europeans, which leaves about 5 % Americans. Also everyone in our lab here is Chinese. Altogether it was a wonderful cultural experience for me, getting an insight into not just the American way of life but in many different ones, too. (e.g. celebrating Chinese New Year in the lab was great fun!)
By American standards the rather old age of the city of Boston makes the architecture very interesting, diverse and beautiful. You’ll see sky-scrapers next to tiny old brick houses. The rents are pretty high, but it’s a really nice place in which to live. Boston is great to experience by walking, biking, or by the public transportation (called the “T”). There are lots of nice little streets with cafés, bars and stores and also big public parks. The only thing that I found a little disturbing was the fact that the “T” service stops around 12:30 am. You get used to it (everyone just goes out earlier, starts drinking and partying earlier)…
Greatest Difficulties Encountered
Finding an affordable room (without mice), and understanding the Chinese accent in English, but eventionally everyone gets used to it
Helpful Hints for Future Students
- Go to www.greyhound.com to book cheaper e-fares for your bus trips (don’t take the Chinatown bus to New York! - bad experience…)
- Go to “Grendel’s Den” at Harvard Square for dinner (Mon. - Fri. 5-7:30pm) good food in a nice bar for half the price
- If you work in Charlestown: a membership for the YMCA (gym, pool, sauna, classes) is only 28$ per month and it is right across the street
- Get a “Deutsche Bank” account and a credit card in Germany. You can withdraw money at Bank of America ATMs for free
- In my opinion, Cambridge and Somerville are the nicest living areas

Must Do's
- If you have any free time (especially in the beginning when your work schedule is not as tight yet) travel as much as you can (New York, Cape Cod, Maine, Vermont, New Hampshire and even Canada are really not that far away and always worth a visit.)
- If you’re interested in wintersports: make a day trip to a ski resort (e.g. Wachussett mountain is very close)

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Abstract on Research Topic

Omega-3 fatty acids in murine hepatocellular carcinoma

Author: Lena Krause

Institution:
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Introduction:
Evidence has been raised that omega-3 polyunsaturated fatty acids (n-3 PUFA) have diverse dampening effects on inflammation and carcinogenesis. This protective effect might be due to their recently identified lipid mediators, which still remains to be further investigated. To examine the influence on carcinogenesis, I induced hepatocellular carcinoma (HCC) with the prototypic chemical carcinogen diethylnitrosamine (DEN) in the transgenic Fat-1 mice and in WT mice (control group). The Fat-1 mouse (generated in the laboratory of Prof. Kang) expresses a desaturase from the roundworm Caenorhabditis elegans which is able to endogenously form n-3 PUFA from n-6 PUFA. Hereby we can analyze the effect of an increased omega-3 PUFA tissue status ruling out the confounding factor of diverging diets.

Materials and Methods:
The mice were sacrificed after 8 months after undergoing a T1 weighted MRI-scan of their livers which enabled us to compare the exact tumor volume, regarding not only the number, but also the size of each tumor nodule. After the sacrifice I removed the liver and seperated it into individual lobes and compared the number of externally visible tumors (≥ 0.5 mm) and there diameters by stereomicroscopy. We compared morphology, steatosis, fibrosis and tumor grading in H&E stained sections of each liver. I am also conducting immunohistochemical stains for COX-2 expression, anti-actin smooth muscle antigen for fibrosis, anti-F4/80 as a Kupffer-cell marker, anti-CD31 (a marker for endothelial cells) and anti-vascular endothelial growth factor (VEGF) for the detection of neovascularization, and anti-proliferation cell nuclear antigen (PCNA) for cell cycle analysis. I determined apoptosis in livers by terminal deoxynucleatide transferase dUTP end nick labeling (TUNEL). To compare NF-kB levels of liver tissue I used an p65-ELISA. Liver injury was also examined by measuring the circulating transaminases alanine transaminase (ALT) and aspartate transaminase (AST) and also tumor necrosis factor alpha (TNF-alpha) levels in serum. Gene expression of TNF-alpha, IL-1beta, IL-6, COX-2, TGF-beta, p53, beta-catenin and 5-lipoxygenase was measured by real-time quantitative PCR. Protein levels were assessed by Western Blot with antibodies to COX-2, beta-catenin, VEGF and PCNA. To compare the levels of different n-3 and n-6 PUFA derived lipid mediators I will conduct a liquid chromatography tandem mass spectrometry analysis (LC-MS/MS). I used gas chromatography for phenotyping and fatty acid analysis of tail and liver tissue, respectively.

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