Tobias Lanz  

Home Institution
Eberhard-Karls-Universität, Tübingen

Host Institution
Stanford University, Stanford, CA
Research Mentor: Lawrence Steinman, M.D., Department of Neurology

E-Mail: tobivlanz@gmail.com
Research Topic
see Abstract
Personal Reactions to the U.S. Experience
Silicon Valley is great! And Stanford is the place to be to do good research!
It’s amazing to experience a different mentality – after two weeks here I knew what a venture capitalist is and how you start your own business using your own idea. No question – that’s what drives people here, but not in a bad way. You immediately get the feeling, that it is your idea which is important and that everything is possible, if it’s good and if you pursue it. And if it doesn’t turn out to be good – never mind, try the next one! It’s a mentality that seems to take much higher risks but is extremely successful. Nothing seems to be impossible and people are very excited and have fun working on their own projects.
San Francisco is nearby, which is one of the most exciting, interesting and beautiful cities I have ever explored. Visit the hippies in Haight Ashbury, go to a gay bar in Castro, have a look at the beautiful museums and art galleries, walk along the Fisherman’s Wharf and across the Golden Gate Bridge and feel like a prisoner in Alcatraz. You will discover new sights every time you go there.
Stanford itself is beautiful as well, especially in the spring and summer. You have all the opportunities in research you can possibly dream of. People are extremely helpful and friendly, and outside the lab they will surely show you the American way of life. I made many friends during the short time I was here, e. g. in the Stanford Symphony Orchestra with which I made an incredibly amazing trip to China.
Directly next to the labs and the businesses there are lots of state- and county parks, which invite you to take a hike, to bike, to run, to go fishing, surfing etc.. The Pacific Ocean is a bit too cold for swimming, but driving down Highway No. 1 is priceless. And, of course, the nearby national parks are a must. Yosemite, Death Valley, Channel Islands etc., in each one you will find a unique landscape and beauty and the most interesting geological or botanical wonders of nature.
Greatest Difficulties Encountered
The greatest difficulty was to waive the tuition which is extremely high in Stanford, even for foreign research scholars who are not allowed to attend classes. I wrote e-mails almost daily for three months because the tuition seemed possible to be waived but apparently it is not. Finally I found another scholarship organization which paid for the tuition during my stay.
Of course the DS-2019! The paperwork was mailed to the U.S. very late and then it was stored unseen at Stanford for several weeks. And you don’t get a DS-2019 as long as you haven’t payed the tuition... When it finally arrived there was a spelling mistake in it – in the end, I got it 5 days before my departure from Germany, just enough time to get the passport back from the consulate and take off.
Most humorous incident
At a rehearsal of the Stanford Symphony Orchestra: The piece is difficult, none of us had really practiced, it sounds quite mysterious for a few minutes, suddenly something feels strange, people stop playing and laugh, the ground and the walls are shaking for about 30 seconds – my first earthquake, which turned out to have a magnitude of 5.6 on the Richter scale. The piece sounded only slightly better afterwords...
Helpful Hints for Future Students
- Don’t think you bother people too much when organizing your stay. Write e-mails relentlessly and call the people in charge until you get the things you need. Don’t think somebody will do administrative work for you.
- Be aware that everything is extremely expensive in the Silicon Valley area.
- A bike is good in order to get from your apartment to the lab, but to reach anything else a car is very helpful.
- Don’t wear your Stanford t-shirt in Berkeley :)
- Never hesitate to ask questions.
- Enjoy your stay – it’s a once-in-a-lifetime experience.

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Abstract on Research Topic

Amelioration of Neuroinflammation using Angiotensin Receptor 1 Inhibitors in a Mouse Model of Multiple Sclerosis
Author: Tobias Lanz

Institution:
Stanford University School of Medicine, Department of Neurology, Stanford, CA

Introduction:
The renin angiotensin aldosterone system (RAAS) is an endocrine system important in regulating blood pressure. In addition there are several independent RAAS in several tissues such as heart, eye, testis or brain, the function of which is not completely understood. Previous studies of the Steinman lab have shown that inhibitors of angiotensin converting enzyme (ACE) have a positive effect on the severity of disease in experimental autoimmune encephalitis (EAE), the most commonly used mouse model of Multiple Sclerosis. We investigated the effect of candesartan, an Angiotensin Receptor 1 (AT1R) inhibitor, in EAE, studying their effect on the cytokine transforming growth factor-b (TGF-b) in various cell types in the brain.

Materials and Methods:
EAE was induced in 8-10 weeks old female C57Bl/6 mice using myelin oligodendrocyte glycoprotein (MOG) peptide 35-55. Severety of disease was scored according to standard protocols. Mice were sacrificed at day 13 (acute disease) and day 21 (recovery). Brains and spinal cords were used for immunohistochemistry stainings of TGF-b and AT1R. Splenocytes and lymph node cells were isolated and restimulated in vitro with MOG p35-55. Activation was measured by uptake of [methyl-3H] Thymidine. Cytokines were measured by ELISA and FACS.
Astrocytes and microglia cells were isolated from newborn C57Bl/6 mice and expanded in vitro for several weeks. After stimulation with Angiotensin II in several combinations with the inflammatory cytokine Interferone-g (IFN-g) and Lipopolysaccharide (LPS), cytokine production was measured by ELISA and by the use of TGF-b reporter cells. qRT-PCR was performed on cDNA of treated astrocytes and microglial cells to investigate the regulation of genes involved in the RAAS during inflammation.

Preliminary Results and Discussion:
In the MOG induced EAE model, AT1R blocker candesartan delayed the onset of disease. We postulate that the delayed onset is due to an inhibition of TGF-b in the brain. Indeed, we found that phosphophorylated-SMAD2, a primary downstream target of the TGF-b signaling pathway, appeared to be decreased in the cerebellum of candesartan treated mice.
In order to elucidate the regulation of TGF-b in vivo we are going to use SBE-luciferase reporter mice, which have a TGF-b-responsive luciferase reporter gene that will reliably indicate activation of TGF-bsignaling, in order to confirm that the AT1R inhibitors are directly targeting the TGF-b signaling pathway. This will be measured by the binding of pSMAD to the SMAD binding element.
We also determined that TGF-b production and SMAD phosphorylation is increased in primary cultures of mouse astrocytes after stimulation with Angiotensin II in combination with IFN-g and LPS. Both can be abrogated by the addition of AT1R inhibitors.
To investigate the direct effect of Angiotensin II on stimulated astrocytes in vitro we will further investigate the proliferation and the cytokine profiles of antigen specific activated T-cells co-cultured in the presence of supernatants from stimulated astrocytes.
We are describing here a unique crosstalk between immune- and nervous system which could be beneficially manipulated. ACE inhibitors and AT1R blockers are already approved and widely used drugs showing very low side effects and almost no effect on blood pressure in normotensive patients. It is a promising tool for treatment of multiple sclerosis.