Hosted by Cardiff University's School of Medicine
The talk will review some of the evolutionary aspects of H2S biology, followed by the regulation of different H2S producing enzymes in mammalian cells. Next, the various biological targets and some of the signaling pathways will be outlined, with special reference to H2S or polysulfide-mediated posttranscriptional modification (sulfhydration) of proteins, and the effect of H2S on various channels and intracellular second messenger pathways, the regulation of gene transcription and translation and the regulation of cellular bioenergetics and metabolism. Finally, the effect of H2S on various physiological and pathophysiological functions will be discussed. From these data, a wide array of significant roles of H2S in the regulation of multiple organ functions emerge and the characteristic bell-shaped of biphasic effects of H2S are highlighted. Two important pathophysiological areas (colon cancer and Down syndrome), where H2S plays important roles and where pharmacological inhibition of H2S biosynthesis is of potential therapeutic benefit will be also presented. Pharmacological modulators of H2S homeostasis are expected to be further investigated in the future and it is hoped that some of these molecules will enter the clinical stage.
Bio: Professor Szabo is an internationally recognized expert in the fields of oxidative and nitrosative stress, gaseous transmitters, cell death, cell dysfunction, cardiovascular, and inflammatory mechanisms. He has pioneered the concept that identified the pathogenetic role of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in promoting cell necrosis, and demonstrated its pathophysiological role in critical illness, cardiovascular and inflammatory diseases, which led to novel drug candidates that have progressed into clinical trials. Much of his recent work has focused on the biology of the novel endogenous gaseous mediator hydrogen sulfide (H2S); he discovered multiple novel roles of H2S in circulatory shock, reperfusion injury, angiogenesis, cancer and Down Syndrome. This work has led to the identification of several novel therapeutic concepts based either on H2S donation or H2S biosynthesis inhibition.
With a H-index of 145 and over 85,000 literature citations, he is one of the most cited pharmacologists in the world. According 2022 Elsevier Worldwide Citation Metrics Index, Prof. Szabo is in the top 1% of the top 2% of all scientists worldwide. He is the recipient of several major awards in pharmacology including the ASPET-Pharmacia award of the American Society of Pharmacology and Experimental Therapeutics and the John Vane Medal of the British Pharmacological Society.
He conducted a postdoctoral fellowship with Nobel Laureate Sir John Vane at the William Harvey Research Institute in London. Between 1994 and 2018, as a professor of Pharmacology, Experimental Surgery and Anesthesiology, he directed several academic groups in the USA. In parallel, he also acted as Chief Scientific Officer of several biotechnology companies which have discovered several first-in-class drug candidates including the first ultrapotent PARP inhibitor that progressed into clinical development.
In 2018, he returned to Europe, where he serves as the Chair of the Department of Pharmacology at the University of Fribourg, Switzerland. He leads a research group that investigates the biological roles of PARP and H2S in health and disease, through employing the combined approaches of pharmacology, physiology, pathophysiology, cell biology, molecular biology, medicinal chemistry and translational science.
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