Dr. Wen Xie is Professor of Pharmaceutical Sciences and Pharmacology, and Director of the Center for Pharmacogenetics. Dr. Xie obtained his MD degree from the Peking University Health Science Center in 1991, and PhD in Cell Biology from the University of Alabama at Birmingham in 1997. He completed a postdoctoral fellowship with Dr. Ronald M. Evans at the Salk Institute in La Jolla, California before joining the University of Pittsburgh in 2002. Dr. Xie holds joint appointment at the Center for Pharmacogenetics, 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 transporters.

Nuclear Receptors: Nuclear receptors belong to a family of ligand-dependent transcriptional factors (Figures 1 and 2). Activation of nuclear receptors will result in gene regulation at the transcriptional level, which will be further translated into the impact on cellular function and physiology. Nuclear receptors are excellent drug targets, and they also represent a unique and pivotal resource to uncover new regulatory systems that impact both health and human diseases.

Nuclear receptor-mediated regulation of drug metabolizing enzymes and transporters: While long studied, the molecular basis of the interactions between the external chemicals (xenobiotics) and the mammalian genome has not been well understood. Such xenobiotics may include clinical drugs and herbal medicines. Research in Dr. Xie’s laboratory has focused on this environment-host interactions and helps to establish members of the nuclear receptor superfamily as the xenobiotic receptors or xeno-sensors that regulate the expression of xenobiotic enzymes and transporters. The prototypical xenobiotic receptors include the pregnane X receptor (PXR) and constitutive androstane receptor (CAR). However, the regulatory function of PXR and CAR can also be shared with or impacted by several other nuclear receptors, such as the liver X receptor (LXR), farnesoid X receptor (FXR), and retinoid-related orphan receptor (ROR). The regulation of drug metabolizing enzymes and transporters has great implications in drug metabolism, drug-drug interactions, and drug toxicity.

The endobiotic function of xenobiotic receptors and their target enzymes: In addition to metabolizing drugs, the same enzyme and transporter systems are also responsible for the homeostasis of numerous endobiotic molecules, such as lipids, glucose, sex hormones and bile acids. For these reasons, both the xenobiotic receptors and their target enzymes have broad implications in many human diseases, including hepatobiliary diseases (cholestasis, gallstone disease, fatty liver, and jaundice), endocrine-related disorders (hormone dependent breast cancer and prostate cancer), and metabolic syndrome (obesity and type 2 diabetes) (Figure 3).

Dr. Xie’s research is conducted using a combination of cell cultures and genetically engineered mice that include transgenic, knockout and humanized mice. Since nuclear receptors are ligand-dependent transcriptional factors, we also routinely use pharmacological models, including the use of receptor agonists and antagonists. We are most interested of the physiological and disease relevance of nuclear receptor-mediated gene regulation. We routinely apply various human disease models in our genetic and pharmacological mouse models.

Dr. Xie is the author of more than 100 journal articles and book chapters and over 115 invited lectures at conferences and universities. Dr. Xie is the 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 50 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.