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March 1, 2018 | 11:00 a.m. - 12:00 p.m.
Category: Seminar
Location: Scott Hall #2268 | Map
540 E. Canfield
Detroit, MI 48201
Cost: Free
Audience: Current Graduate Students, Faculty, Staff

Thomas Kocarek, PhD

Professor, Institute of Environmental Health Sciences, Wayne State University

“Regulation of Xenobiotic-Metabolizing Enzymes by Sterols and Isoprenoids”


Xenobiotic metabolism is the process by which one exogenous chemical is converted to another. Xenobiotic metabolism usually converts lipophilic chemicals that would tend to persist in the body into hydrophilic chemicals that are more readily excreted. Xenobiotic-metabolizing enzymes are often classified into the phase I enzymes that introduce or expose a functional group on a substrate molecule (exemplified by the cytochromes P450), and the phase II enzymes that conjugate a functional group on a substrate with an endogenous molecule (exemplified by the UDP-glucuronosyltransferases and cytosolic sulfotransferases [SULTs]). Xenobiotic-metabolizing enzyme expression is regulated by endogenous and exogenous signals, and many of these effects are transduced through nuclear receptors such as the “xenobiotic-sensing” receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Our lab is studying the regulation of xenobiotic-metabolizing enzymes by intermediates of the cholesterol biosynthetic pathway, and we have demonstrated that both the more proximal isoprenoid and more distal sterol metabolites of the pathway are capable of modulating xenobiotic-metabolizing enzyme expression. This seminar will present (1) our work on isoprenoid- and sterol-mediated regulation of the SULT1C2 gene in primary cultured rat hepatocytes and (2) our recent studies demonstrating that inhibition of cholesterol biosynthesis interferes with CAR function in human hepatocytes. This latter finding may be relevant to the observation that some patients who take statin drugs to control hypercholesterolemia develop diabetes mellitus.

For more information about this event, please contact Suzanne Shaw at 577-5325 or