We are pleased to invite the campus community and colleagues to Wayne State University’s Integrative Environmental Health Sciences Seminar Series. The series is hosted by Wayne State’s CURES P30ES036084 Environmental Health Sciences Core Center and the CLEAR P42 Superfund Research Program.

Our next seminar will be held on March 27, 2025 from 12:30 to 1:30 p.m. EST via Zoom. Zoom details will be emailed to all registrants.

The guest speaker will be Dr. Yoichi Osawa, the Warner-Lambert, Parke-Davis Professor in Medicine, and a professor of pharmacology in the University of Michigan Medical School. He will present, "Toxicological perspectives on the regulation of cytochrome P450 NO synthase by chaperones."

Abstract:

Drugs and xenobiotics are often metabolized by cytochrome P450 enzymes to reactive intermediates, which often lead to toxicity. The initial target of these reactive intermediates is the P450 enzyme leading to covalent alteration, inactivation, and targeting of the enzyme for ubiquitination and degradation. Osawa will discuss how Hsp90 and Hsp70 chaperones selectively recognize the covalently altered P450 cytochromes and recruit chaperone-dependent ubiquitin ligases to mark the enzymes for degradation. These findings are thought to be significant in understanding the fundamental biological process of heme insertion into P450 and maintenance of functional enzyme levels. Understanding the regulation quality and quantity of P450 cytochromes is important in understanding drug-drug interactions and xenobiotic toxicity.

Biography:

Dr. Osawa is currently the Warner-Lambert, Parke-Davis Professor in Medicine, and a professor of pharmacology in the University of Michigan Medical School. He received his B.S. in Chemistry from MIT and Ph.D. in pharmacology from the University of Michigan. He was a Fogarty fellow and senior staff fellow in the Lab of Chemical Pharmacology at the National Heart Lung and Blood Institute at the National Institutes of Health (NIH) before joining the pharmacology department at Michigan in 1995. His studies focus on the chemical mechanisms of inactivation of P450 enzymes, including nitric oxide synthase (NOS), and their role in toxicity. He has published seminal studies on the inactivation, alteration, and degradation of P450 cytochromes and the role of Hsp90 and Hsp70 in maintaining protein quality control of the P450. He discovered that Hsp90 and Hsp70 chaperones mediate heme insertion into heme-deficient apo-NOS, by a process that is now recognized as a novel mechanism of hemeprotein regulation. He has received a Toxicology Award from Burroughs Wellcome Fund, an Established Investigator Award from the American Heart Association, and a Henry Russel Award from the University of Michigan for scholarship and teaching.