Johan Matthes Lorenzen  

Home Institution
Medizinische Hochschule Hannover

Host Institution(s)
Albert Einstein College of Medicine, Bronx, New York
Division of Nephrology
Mentor: Katalin Susztak, M.D., Ph.D.

E-Mail: jolo90@aol.com

Research Topic
see Abstract
Personal Reactions to the U.S. Experience
Ever since I had spent a school-year in the U.S. in 1996, I wanted to come back to this country. I wanted to experience the friendliness and open-mindedness again, two qualities, which have actually almost become a cliché in the European, if not the global, perception of the U.S.. At this point, I remember one Indian friend of mine referring to the United States as being the "land of milk and honey". I would not go that far. Nervertheless, I have to admit, that my expectations were not disappointed.
Initially, when I first came to New York, I had a little trouble finding the appropriate accomodation. But it only took one instant before the technical assistant working in my lab, who is an American, offered me a place to sleep for a couple of days. When I had actually found a place, she offered me her desk for the time being, since my apartment, to say the least, was only poorly furnished.
And, of course, there is New York. I do not know how many students taking part in the "Biomedical Sciences Exchange Program" before me also lived in this city. I suppose you have all read their praise and their excitement felt for this "melting pot". I do not intend to be the exception to this. The variety of different cultures is just beyond imagination. On one particular day I would have dinner at an authentic Chinese restaurant in Flushing, Queens, an area, which luckily is not yet thronged with tourists. On the next day I would buy food on "Arthur Avenue", the less well known "Little Italy" of the Bronx. I do not think that I have to lecture anyone about the renowned museums in Manhattan, or about seeing an opera at the Metropolitan Opera House at Lincoln Center.
All these different points that I have mentioned so far were somewhat imaginable. What struck me was the way research is being done in this country. It seems that scientists have endless financial resources available to them. The way money is spent runs almost contrary to what Europeans are accustomed to. Whenever our lab ran out of something, no matter how expensive, it was ordered anew.
On the whole, these months in the U.S. were probably among the most exciting throughout all my time in Medical School.
Greatest Difficulties Encountered
As far as my research time here at "Einstein" is concerned, problems have yet to arise. I did experience difficulties organizing a clinical elective, but once Dr. Stolte called the registrar these were immediately resolved.
Most humorous incident
Too many to tell!
Best professional experience:
It is impossile for me to single out one particular experience. For one, I really admired the pragmatic approach towards "problem solving", that almost seems inherent to Americans. As I mentioned before, I was flabbergasted to be able to work with such few financial restrictions. Another main difference between the German and the American research communities was that my Principal Investigator was around all day. She never disappeared to the hospital, nowhere to be found. I could always approach her to ask questions when my work got stuck. Due to her intelligence and experience I greatly benefitted from my time in this laboratory.

Best Personal Experience:
Having spent most of my studies in Hannover, a medium-sized city in the north of Germany, it was a big transition for me to live in the global metropolis of New York. Again, I apologize for disappointing those reading these lines for my inability to single out one outstanding experience. For me it was the combination of all those different opportunities in this environment, that I have only partly mentioned, that made this time so memorable on the whole.
In conclusion, I want to thank Dr. Stolte and the Biomedical Sciences Exchange Program for enabling me to expand my horizons in this awe-inspiring way.

Helpful Hints for Future Students
  • open up a bank account at Citibank, and for housing look on craigslist
  • with a valid I.D. students can attend operas at the Metropolitan Opera House for $25
  • get a prepaid phonecard from Verizon, which can be used in European TRI-BAND cell phones

Johan Lorenzen at the Museum of Modern Art in New York

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Abstract on Research Topic
The Role of Osteopontin in Podocyte Injury
Background:
Osteopontin is a highly acidic phosphoprotein, first isolated from bone, but also expressed in several other tissues, including renal tubular epithelium. OPN-expression is implicated in a wide array of pathophysiological processes, including bone remodeling and osteoporosis, tumor metastasis, vascular pathology and wound healing. In the normal kidney, OPN is mainly produced by the distal nephron and secreted into urine, where it may serve to prevent urinary stone formation. OPN up-regulation has been demonstrated in several experimental models of renal disease. However, the precise mechanism in which OPN is functioning in renal pathophysiology remains unclear.
Osteopontin has been described as a macrophage chemoattractant and its up-regulation in renal disease is also implicated in tubulointerstitial fibrosis.
Osteopontin may act as survival factor for cells through inhibition of apoptosis.

Methods:
Injection of C57BL/6 mice and SPP1-/- (6 weeks of age) with LPS, after 24h measurement of proteinuria level via dipstick analysis and sacrification of mice. Akita mice (16 weeks of age) were put into metabolic cages for 24h-urine-collection. For each experiment renal tissue was obtained for immunohistochemical studies and QRT-PCR studies.
Mouse podocytes in cell culture were treated with various activators and inhibitors of the p38-MAPK pathway, the ERK-pathway and PKC-pathway, were also treated with various other stimuli. Subsequently, the cDNA, that was obtained from these cells, was used for QRT-PCR. Following Synaptopodin/WT-1 staining the level of apoptosis was evaluated. Western-Blotting analysis of OPN protein.

Results:
OPN knockout mice are protected from the development of proteinuria as compared to C57BL/6 CTL-mice. Glucose-, LPS-, TGF beta- and EGF- treatments lead to an upregulation of OPN, whereas inhibitors of the PKC pathway prevent this upregulation from occuring. Immunohistochemical studies also show this upregulation in tissue samples obtained from LPS injected C57BL/6 mice compared to SPP1-/- and CTL mice. Podocytes treated with OPN show cell-cycle arrest.