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 the Xie lab has helped to establish members of the orphan nuclear receptor family, 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, colon cancer, and metabolic syndrome.
To better understand the transcriptional regulation of enzymes and transporters and the significance of this regulation in vivo, the 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 orphan nuclear receptor-mediated gene regulation through molecular, genomic, and pharmacological approaches. Research in the Xie lab has been funded by the National Cancer Institute (NCI), National Institute of Environmental Health Sciences (NIEHS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Child Health and Development (NICHD), National Center for Complementary and Alternative Medicine (NCCAM), Department of Defense (DOD), Susan G. Komen Breast Cancer Research Foundation, and the American Heart Association (AHA). 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, the American Society for Pharmacology and Experimental Therapeutics (ASPET) Division for Drug Metabolism Early Career Achievement Award, and the Joseph Koslow Endowed Chair in Pharmaceutical Sciences.