[Lfm] Reminder Today 4pm Seminar (Zoom Only) - Partitive H Patel

[Nic Tapon]

A reminder for our seminar today at 4pm.
Parthive H. Patel
Group Leader, Wellcome Trust Royal Society Sir Henry Dale Fellow,<https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.gutstresslab.org%2F&data=04%7C01%7C%7C82524763faa944b585d308d8a1a49231%7C4eed7807ebad415aa7a99170947f4eae%7C0%7C0%7C637437075589038242%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=%2Fg5GniFIpFi9YLUfTnhE9dNehf85e7BMz%2Fh5iCnQ1Ms%3D&reserved=0>
School of Cellular and Molecular Medicine, University of Bristol<https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.gutstresslab.org%2F&data=04%7C01%7C%7C82524763faa944b585d308d8a1a49231%7C4eed7807ebad415aa7a99170947f4eae%7C0%7C0%7C637437075589038242%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=%2Fg5GniFIpFi9YLUfTnhE9dNehf85e7BMz%2Fh5iCnQ1Ms%3D&reserved=0>

will talk on
‘Stress Signalling in Intestinal Regeneration and Tumorigenesis’

This will be a zoom seminar, please join using the link or meeting ID & password below

https://crick.zoom.us/j/66299473817?pwd=NjlOQ0NNV1M5K093N0xFdjRaU21udz09<https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fcrick.zoom.us%2Fj%2F66299473817%3Fpwd%3DNjlOQ0NNV1M5K093N0xFdjRaU21udz09&data=04%7C01%7C%7C82524763faa944b585d308d8a1a49231%7C4eed7807ebad415aa7a99170947f4eae%7C0%7C0%7C637437075589048234%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=tQin4N1%2Fs6B%2Fh63rbyvu6wCMx405p8DREcttWRAyIWU%3D&reserved=0>


Meeting ID: 662 9947 3817/Passcode: 412807

Please mute your microphone when joining
To ask a question at the end of the talks, please type “Question” in the chat. The chair will then instruct you when to unmute and ask your question


Abstract
Many epithelial tissues, like our skin or gut, need to defend themselves constantly against environmental stresses (e.g. from pathogens, chemical, mechanical insults). When these epithelial cells are damaged or lost, they are often replaced by stem cells. Thus, an epithelium’s ability to sense stress, defend itself and stimulate stem cell proliferation is vital to maintain its proper cell number and integrity, thereby preventing tissue dysfunction, degeneration, inflammation and disease. On the other hand, these same processes that promote regeneration, if left unchecked, could also stimulate uncontrolled proliferation, causing hyperplastic and tumorous overgrowth.
I will describe in the adult Drosophila intestine how stress signalling in epithelial cells senses damage and promotes stem cell-mediated epithelial regeneration and how early stem cell-derived tumours can initiate and grow by harnessing signals produced by stressed, but otherwise normal, neighbouring epithelial cells.
Biography
Parthive was born and raised near Chicago, IL, USA.After obtaining his B.A. in Chemistry from the University of Chicago, he attended graduate school at the University of California, Los Angeles (UCLA), where he obtained his Ph.D. in Molecular Biology. During his doctoral thesis work, he discovered a novel regulator of Target of Rapamycin (TOR) signaling and cellular growth. TOR signalling promotes cellular growth and is negatively regulated by the GTPase activating protein, Tuberous Sclerosis Complex 2 (TSC2). But how TSC2 inhibits TOR activity was unknown. He showed that the small GTPase, Rheb, can promote cell growth through TOR signalling (Journal of Cell Science, 2003), thus providing this crucial link. Rheb is yet the foremost, direct positive regulator of TOR and is relevant to many diseases such as cancer, obesity and diabetes. After obtaining his Ph.D., he was an American Cancer Society postdoctoral researcher with Dr. Bruce Edgar, first at the Fred Hutchinson Cancer Research Center in Seattle, USA and then later at the Centre for Molecular Biology, University of Heidelberg (ZMBH) and the German Cancer Research Center (DKFZ) in Heidelberg, Germany. During his postdoc, he first showed that damaged adult fly intestines regenerate through ISC divisions (Jiang et al., 2009, Cell). This work helped establish this model to study adult epithelial regeneration. He then showed that various stresses cause IECs to produce reactive oxygen species via NADPH Oxidase which stimulate p38 stress signalling and mitogen production by IECs, that promote ISC proliferation (Nature Communications, 2019). As p38 is also required for mammalian intestinal regeneration, this work indicates how and where damage activates p38. This work is highly relevant to pathological conditions with chronic IEC damage such as inflammatory bowel diseases, which increase colorectal cancer risk. He also demonstrated that Drosophila ISC tumours appropriate the niche to grow. Epithelial tumour-initiating cell pool size is thought to expand from successive, secondary mutations that promote growth and survival. He showed that differentiation-defective stem cell-derived tumours (Notch-) in the fly intestine initially grow by displacing normal neighboring niche IECs and by co-opting mitogenic signals produced by these stressed or dying IECs. Furthermore, he found that ISC tumours initiated and grew faster within stressed epithelia (Nature Cell Biology, 2015). This work highlights strategies to target early epithelial tumorigenesis by mitigating stress signalling or cell death in normal epithelial cells surrounding tumours or tumour-initiating cells. Furthermore, this work helped establish this model to study adult epithelial tumorigenesis.





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