Current Research:

Dr. Xie’s laboratory studies orphan nuclear receptor-mediated regulation of genes encoding drug metabolizing enzymes and transporters. The same enzymes and transporters are also responsible for the homeostasis of endogenous chemicals (endobiotics) that include steroid hormones, cholesterol, lipids, bile acids and bilirubin. Research in Xie lab has helped to establish members of the orphan nuclear receptors, such as PXR (pregnane X receptor), CAR (constitutive androstane receptor), LXR (liver X receptor) and ROR (retinoid-related orphan receptor), as xeno- and endo-sensors that sense xeno- and endobiotics which, in turn, lead to enzyme and transporter gene regulation. This regulation has broad implications in drug metabolism and drug development. Moreover, these orphan receptors can be explored as therapeutic targets for the treatment and prevention of human diseases, such as cholestasis, jaundice, gallstone disease, breast cancer, prostate cancer, and colon cancer.
To better understand the transcriptional regulation of enzymes and transporters and the significance of this regulation in vivo, Xie lab has created a wide array of genetic engineered mice with compromised (gene knockout), heightened (transgenic), or humanized receptor activities. The humanized mice, created by replacing the mouse receptor with its human counterpart, have provided unique tools to dissect the orphan nuclear receptor-mediated gene regulation through molecular, genomic, and pharmacological approaches.

Research in Xie lab has been funded by National Cancer Institute (NCI), National Institute of Environmental Health Sciences (NIEHS), National Center for Complementary and Alternative Medicine (NCCAM), Department of Defense (DOD), and the Susan G. Komen Breast Cancer Research Foundation. Dr. Xie is the recent recipient of the 2008 James R. Gillette International Society for the Study of Xenobiotics (ISSX) North American New Investigator Award, and 2009 American Society for Pharmacology and Experimental Therapeutics (ASPET) Division for Drug Metabolism Early Career Achievement Award.

Bio:

Wen Xie (MD, PhD) is currently Associate Professor of Pharmaceutical Sciences and Pharmacology. Dr. Xie obtained his MD degree from Peking University Health Science Center in 1991, and PhD in Cell Biology from University of Alabama at Birmingham in 1997. He completed a postdoctoral fellowship (1998-2002) with Dr. Ronald M. Evans at the Salk Institute in La Jolla, California. Dr. Xie joined the University of Pittsburgh in 2002. Dr. Xie holds joint appointment at the Center for Pharmacogenetics and Department of Pharmaceutical Sciences at the School of Pharmacy and Department of Pharmacology and Chemical Biology at the School of Medicine. The research focus of Dr. Xie's laboratory is nuclear receptor-mediated transcriptional regulation of genes that encode drug metabolizing enzymes and drug transporters. This regulation has broad implications in drug metabolism and many human diseases, including hepatobiliary diseases, endocrine disorders, metabolic syndrome, and cancers. Dr. Xie’s research is conducted using a combination of cell cultures and genetically engineered mice that include transgenic, knockout and humanized mice. Dr. Xie is the author or coauthor of nearly 80 journal articles and book chapters and over 90 invited lectures at conferences and universities. Dr. Xie is the sole editor of "Nuclear Receptors in Drug Metabolism", a book published by Wiley in 2008. Dr. Xie currently serves as ad hoc reviewer for NIH and DOD Study Sections and for over 20 scientific journals. Among his achievements, Dr. Xie is the recipient of the University of Pittsburgh Chancellor’s Distinguished Research Award, the James R. Gillette International Society for the Study of Xenobiotics (ISSX) North American New Investigator Award, and the American Society for Pharmacology and Experimental Therapeutics (ASPET) Division for Drug Metabolism Early Career Achievement Award.