Sören Pischke

Home Institution
Albert-Ludwigs-Universität Freiburg i.Br.

Host Institution
University of Pittsburgh, Dept. of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Research Mentor: Augustine MK Choi
Clinical Rotation: 4 weeks of critical care medicine, 2 weeks of pulmonary and 2 weeks of allergy medicine

E-Mail: spischke@web.de

Research Topic
see Abstract
Personal Reactions to the U.S. Experience
Pittsburgh.... First of all, where is that town and second, isn't it the place called "the dirtiest town in the U.S." because of the steel and coal industries? These are probably the most common questions I am asked when I am talking about my stay here in the U.S. To answer the first question: Pittsburgh is located two hours south of Lake Erie and four hours west of Philadelphia, but they consider themselves to be on the east coast. Pittsburgh may not be the most picturesque or richest town in the U.S., but it's definitely not as bad as the picture one might have of an old industrial town. These days, after almost all the traditional industries closed down, Pittsburgh is developing fast into a center of education (with two of the leading universities in the country - at least in basketball), computer science, biotechnology and medicine. That's why a lot of effort is taken to increase the quality of life. For students like me, living on a tight scholarship, this offers great opportunities: living is cheaper than in many other places on the east coast, there are uncountable bars, restaurants, hidden clubs, concerts, microbreweries (and this kind of American beer is good!!), a lot of green and a great variety of recreational possibilities to explore. Additionally, this place is not "overrun" by foreign students. That does not mean that you are "special", but rather everybody is very interested in what you are doing. I have found it easy to make very good friends. In sum, I would say, that I have liked the stay in the U.S., especially in Pittsburgh, much more than I had expected. I want to come back for a longer stay and I am really happy that I was offered this opportunity!
Most humorous incident
I was not able to eat at Taco Bell because of my inability to understand the question: "For here, to go?" Trying to understand the non-understandable and very unstable dating rules.
Helpful Hints for Future Students
- When you are getting only half of the DAAD funding, try to get the other half from other organizations. I tried the Else-Kroener-Fresenius Stiftung. The application was very easy (much easier than for BMEP) and I got some additional money!
- If you want to come to Pittsburgh, mail the Pittsburgh Council for International Visitors (PCIV) some time in advance (www.pciv.org). They will arrange a host family for the first two weeks and then you will have enough time to easily find a cheap and reasonable apartment.
- Live in a shared apartment - more fun, lesser costs and a free English teacher (if you don't mind cleaning for other people!)
- If you have the possibility, go to college parties - you will be reminded of the good old times when you were 16.
- In every LOEWS movie complex there is a Bank of America ATM. So, enjoy a lot of movies and get money from your Deutsche Bank account without paying a fee and get the best currency rate possible.
- In UPMC (the hospitals in Pittsburgh) it is possible to make "Famulaturen" without paying extra-money. When applying for research, mention that you want to work in the clinic as an "observer of sort" and that this is mandatory for your scholarship.

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Abstract on Research Topic
The Phosphatidylinositol 3-Kinase Inhibitor Wortmannin Inhibits Hemeoxygenase-1 Expression

Authors
Soeren E. Pischke, Wen Ning and Augustine MK Choi

Institution
Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, PA
Purpose
The purpose of this study is to demonstrate that the expression of HO-1 may be regulated through the PI3K/Akt pathway. Stimulation of Phosphatidylinositol-3-Kinase (PI3K), through oxidative and inflammatory stress, leads to subsequent activation of Akt and an increase of antiapoptotic and cell protecting proteins. Hemeoxygenase-1 (HO-1) catalyzes the first and rate-limiting step in heme catabolism, causing the oxidative cleavage of heme to yield equimolar quantities of iron, carbon monoxide (CO) and biliverdin. The fact that heme is a potent pro-oxidant while biliverdin is an equipotent antioxidant and that it was shown that CO has anti-inflammatory effects, has led to the postulate that HO-1 is a component of the cellular defense mechanism against oxidative and inflammatory stress. Given these findings, it seems plausible to investigate a hypothetical link between PI3K/Akt activation and HO-1 expression.
Materials and Methods
HO-1 reportergen assays were performed after transient-transfection of rat primary macrophage cells (RAW 264.7) with a vector containing the HO-1 promoter site cloned in front of a luciferase-reportergen, followed by a treatment with the PI3K-inhibitor Wortmannin (W) and Lipopolysaccharide (LPS). HO-1 immunoblotting and Nuclear-factor-kB (NF-kB) elctrophoretic mobility shift assays (EMSA) were carried out using whole cell extract of RAW 264.7 cells, which were treated with W and subsequently stimulated with LPS. Nuclear protein extracts were prepared for Activator-Protein-1 (AP-1) EMSA of identically treated RAW 264.7 cells.
Results
Reportergen assays showed in LPS stimulated cells that a W treatment reduces the HO-1 reportergen-expression to about 50% compared to untreated controls. To assess, if treatment with W results in an altered HO-1 protein-expression, cells were treated with W and the protein-expression of HO-1 was measured. W reduced the expression of HO-1 to levels comparable to an unstimulated control in a dose-dependent manner. To asses through which transcription factor W inhibits HO-1 protein-expression, EMSA for NF-kB and AP-1 were performed. DNA-binding-activity of these transcriptionfactors was not impaired by W.
Discussion
To date, the results demonstrate that there may be a possible link between the PI3K/Akt-pathway and an altered HO-1-genexpression. This was shown by an inhibition of a reportergen and a reduced protein-expression of HO-1 through W. Therefore, our future goal is to describe the transcriptional mechanism responsible for the altered expression of HO-1 by EMSA because AP-1 and NF-kB most likely are not responsible for these inhibitory effects. Furthermore, we sought to determine whether PI3K or Akt is crucial in the regulation of the HO-1 gene, using cells expressing dominant-negative forms of the respective proteins. The interaction between the PI3K/Akt signaling pathway and the expression of HO-1 may be of particular importance in explaining some of the cell-protecting effects seen after an activation of the PI3K/Akt pathway.