Seminar - Professor Gabor J Tigyi
| Dates: | 28 August 2019 |
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| Times: | 11:00 - 12:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Biology, Medicine and Health |
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| Who is it for: | University staff, Adults, Current University students |
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| Speaker: | Prof Gabor J Tigyi |
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Professor Gabor J Tigyi will present a talk on 'LPA-Autotaxin Axis in the Communication of Neoplastic Cells with the Tumor Microenvironment'
Abstract:
Cancer metastasis (MET) and development of resistance to therapy limit survival in most types of cancers. The lack of drugs that reverse therapy resistance and inhibit MET is a critical barrier to successful therapy. Our previous research began addressing this problem by identifying the autotaxin (ATX) – the lysophospholipase D that generates the lipid growth factor lysophosphatidic acid (LPA) – axis as a key regulator of MET and therapy resistance.
In this presentation we will discuss our results on the effect of radiation-induced reprogramming of fibroblasts of the tumor microenvironment. We will also present the results of experiments utilizing inhibitors of ATX and the impact of CRISPR-Cas9-mediated KO in ovarian carcinoma and melanoma progression in orthotopic xenograft models. We will demonstrate the effect of LPA2 GPCR inhibition on breast cancer stem-like cell growth and survival. Lastly, we will present our newest data on the inhibitory action of the LPA5 receptor on the anti-tumor cytotoxic CD8 T cell response. These results taken together indicate a major role of the ATX-LPA GPCR axis in tumor progression and the development of the tumor microenvironment. (Supported by NCI CA092160 and the Van Vleet Oncology Endowment)
Biography:
Professor Tigyi is Harriet Van Vleet Professor of Physiology and Professor of Pharmaceutical Sciences and the University of Tennessee Health Science Center Memphis, USA.
His work has focused on the physiological and pathophysiological role of lysophospholipid mediators. Since 1987, when he discovered lysophosphatidic acid (LPA) as a bioactive serum factor, his research focuses on the isolation, biochemical structure elucidation, molecular target identification and cellular signaling of LPA and sphingosine-1-phosphate (S1P). He is a cofounder of RxBio, co-discoverer of LPA, an inventor of the autotaxin inhibitors.
According to his peers, he has made seminal contributions to LPA biology and pathophysiology with over 220 publications on this topic and over 14,208 citations. His group has identified lysosphingomyelin, cyclic phosphatidic acid, and alkenyl glycerophosphate as novel members of the growth factor-like lysophospholipid family. They reported the first LPA1 receptor-selective inhibitor in 1998. Since the mid-nineties, they have been elucidating the molecular pharmacology of lysophospholipid targets, developed and applied computational chemical methods for drug discovery. This chemical biology work yielded several patents and a rationally designed LPA mimetic, octadecenyl thiophosphate (OTP/Rx100) that has been tested in non-human primates and was entered the FDA approval process on the fast track for the treatment of radiation injury.
Professor Tigyi has helped train 50 fellows and postdocs from the US, Europe and Japan. His work has been funded by NIAID and NCI highlighted with several dozens of high impact factor publications yielding a Hirsch index 66.
Speaker
Prof Gabor J Tigyi
Role: Harriet Van Vleet Professor of Physiology
Organisation: University of Tennessee Health Science Center
Travel and Contact Information
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Lecture Theatre 5
Stopford Building
Manchester
