Wen Xie (MD, PhD) is Professor of Pharmaceutical Sciences and Pharmacology, Director of the Center for Pharmacogenetics, and Joseph Koslow Endowed Chair in Pharmaceutical Sciences. 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 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 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. In addition to metabolizing drugs, the same enzyme and transporter systems are also responsible for the homeostasis of numerous endobiotic molecules. Therefore, 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 more than 100 journal articles and book chapters and over 120 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 has served 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 (2008), the James R. Gillette International Society for the Study of Xenobiotics (ISSX) North American New Investigator Award (2008), the American Society for Pharmacology and Experimental Therapeutics (ASPET) Division for Drug Metabolism Early Career Achievement Award (2009), and the Joseph Koslow Endowed Chair in Pharmaceutical Sciences (2012).
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, colon cancer, and metabolic syndrome.
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 Institute of Diabetes and Digestive and Kidney Diseases. National Center for Complementary and Alternative Medicine (NCCAM), Department of Defense (DOD), Susan G. Komen Breast Cancer Research Foundation, and American Heart Association (AHA). Dr. Xie is the recipient of University of Pittsburgh Chancellor’s Distinguished Research Award (2008), James R. Gillette International Society for the Study of Xenobiotics (ISSX) North American New Investigator Award (2008), and American Society for Pharmacology and Experimental Therapeutics (ASPET) Division for Drug Metabolism Early Career Achievement Award (2009), and the Joseph Koslow Endowed Chair in Pharmaceutical Sciences (2012).
Selected research articles since 2008:
Gong H, Jarzynka MJ, Cole TJ, Lee JH, Wada T, Zhang B, Gao J, Song WC, DeFranco DB, Cheng SY, Xie W. Glucocorticoids antagonize estrogens by glucocorticoid receptor-mediated activation of estrogen sulfotransferase. Cancer Research 68: 7386-7393 (2008)
Lee JH, Gong H, Khadem S, Lu Y, Gao X, Li S, Zhang J, Xie W. Androgen deprivation by activating the liver X receptor. Endocrinology 149: 3778-3788 (2008)
Uppal H, Zhai Y, Gangopadhyay A, Khadem S, Ren S, Moser JA, and Xie W. Activation of LXR sensitizes mice to gallbladder cholesterol crystallization. Hepatology 47: 1331-1342 (2008)
Wada T, Kang SH, Angers M, Gong H, Bhatia S, Khadem S, Ren S, Ellis E, Strom SC, Jetten AM, and Xie W. Identification of oxysterol 7a-hydroxylase (Cyp7b1) as a novel RORa target gene and a functional crosstalk between RORa and LXR. Molecular Pharmacology 73: 891-899 (2008)
Zhou J, Liu M, Zhai Y, and Xie W. The anti-apoptotic role of pregnane X receptor in human colon cancer cells. Molecular Endocrinology 22: 868-880 (2008)
Zhou J, Febbraio M, Wada T, Zhai Y, Kuruba R, Khadem S, He J, Lee JH, Ren S, Li S, Silverstein RL, and Xie W. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR and PPARg in promoting steatosis. Gastroenterology 134: 556-567 (2008)
Gong H, He J, Lee JH, Mallick E, Gao X, Li S, Homanics GE, Xie W. Activation of the liver X receptor prevents lipopolysaccharide-induced lung injury. J Biol Chem. 284: 30113-30121 (2009)
Gao J, He J, Zhai Y, Wada T, Xie W. The constitutive androstane receptor is an anti-obesity nuclear receptor that improves insulin sensitivity. J Biol Chem. 284: 25984-25992 (2009)
Zhang B, Cheng Q, Ou Z, Lee JH, Xu M, Kochhar U, Ren S, Huang M, Pflug BR, Xie W. Pregnane X receptor as a therapeutic target to inhibit androgen activity. Endocrinology 151: 5721-5729 (2010)
Zhai Y, Wada T, Zhang B, Khadem S, Ren S, Kuruba R, Li S, Xie W. A functional crosstalk between LXRa and CAR links lipogenesis and xenobiotic responses. Mol Pharmacol 78: 666-674 (2010)
Kang HS, Okamoto K, Kim YS, Takeda Y, Bortner CD, Dang H, Wada T, Xie W, Yang XP, Liao G, Jetten AM. Nuclear orphan receptor TAK1/TR4-deficient mice are protected against obesity-linked inflammation, hepatic steatosis, and insulin resistance. Diabetes 60: 177-188 (2010)
Lee JH, Wada T, Febbraio M, He J, Matsubara T, Lee MJ, Gonzalez FJ, Xie W. A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis. Gastroenterology 139: 653-63 (2010)
Ou Z, Wada T, Gramignoli R, Li S, Strom SC, Huang M, Xie W. MicroRNA hsa-miR-613 targets the human LXRα gene and mediates a feed-back loop of LXRα autoregulation. Mol Endocrinol 25: 584-596 (2011)
He J, Nishida S, Xu M, Makishima M, Xie W. PXR prevents cholesterol gallstone disease by regulating biosynthesis and transport of bile salts. Gastroenterology 140: 2095-2106 (2011)
Wada T, Ihunnah CA, Gao J, Chai X, Zeng S, Philips BJ, Rubin JP, Marra KG, Xie W. Estrogen sulfotransferase inhibits adipocyte differentiation. Mol Endocrinol 25: 1612-1623 (2011)
Saini SPS, Zhang B, Niu Y, Jiang M, Gao J, Zhai Y, Lee JH, Uppal H, Tian H, Tortorici MA, Poloyac SM, Qin W, Venkataramanan R, Xie W. Activation of LXR increases acetaminophen clearance and prevents its toxicity in mice. Hepatology 54: 2208-2217 (2011)
Gao J, He J, Shi X, Stefanovic-Racic M, Xu M, O'Doherty RM, Garcia-Ocana A, Xie W. Sex-specific effect of estrogen sulfotransferase (EST) on mouse models of type 2 diabetes. Diabetes 61: 1543-1551 (2012)
Gao J, Xie W. Targeting xenobiotic receptors PXR and CAR for metabolic diseases. Trends Pharmacol Sci. 33: 552-558 (2012)
Ou Z, Shi X, Gilroy RK, Kirisci L, Romkes M, Lynch C, Wang H, Xu M, Jiang M, Ren S, Gramignoli R, Strom SC, Huang M, Xie W. Regulation of the human hydroxysteroid sulfotransferase SULT2A1 by ROR alpha and ROR gamma and its potential relevance in human liver diseases. Mol Endocrinol 27: 106-115 (2013)
Chai X, Zeng S, Xie W. Nuclear receptors PXR and CAR: implications for drug metabolism regulation, pharmacogenomics and beyond. Expert Opin Drug Metab Toxicol. 2013 Jan 17. [Epub ahead of print]
Jiang M, Xie W. Role of the constitutive androstane receptor in obesity and type 2 diabetes, a case study of the endobiotic function of a xenobiotic receptor. Drug Metab Rev. 45: 156-163 (2013)
He J, Gao J, Xu M, Ren S, Stefanovic-Racic M, O'Doherty RM, Xie W. PXR ablation alleviates diet-induced and genetic obesity and insulin resistance in mice. Diabetes 2013 Jan 24. [Epub ahead of print]
Selected presentations since 2009 (outside University of Pittsburgh):
Wadsworth Center Seminar, New York State Department of Health, Albany, NY. March 26, 2009
Salk Symposium on Nuclear Receptors, The Salk Institute for Biological Sciences, La Jolla, CA. April 17, 2009.
Lecture as the awardee of the 2009 American Society for Pharmacology and Experimental Therapeutics (ASPET) Division of Drug Metabolism Early Career Achievement Award, Experimental Biology 2009/ASPET, New Orleans, LA, April 18-22, 2009
Laboratory of Pharmacology and Molecular Toxicology (LP/LMT), National Institute of Environmental Health Sciences (NIEHS), NIH, Research Triangle Park, NC. April 30, 2009.
16th North American ISSX Meeting (as Speaker and Session Chair), Baltimore, MD. October 18-22, 2009.
The Hamner Institutes for Health Sciences, Research Triangle Park, NC. October 29, 2009.
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas. November 24, 2009.
Keystone Symposium on Nuclear Receptors: Development, Physiology and Disease, Keystone Resort in Keystone, Colorado, Mar 21-26, 2010.
College of Life Science, Beijing Normal University. Beijing, China. April 30, 2010.
Department of Physiology and Pathophysiology, Peking University Health Science Center. Beijing, China. May 5, 2010.
School of Basic Medical Sciences, Capital Medical University, Beijing, China. May 7, 2010.
Nanjing International Symposium on Pharmacogenomics and the Regulation of Drug Metabolism Enzymes and Genes (as Speaker and Session Chair), Nanjing, China, May 12-15, 2010.
2010 Microsomes and Drug Oxidations (MDO) Meeting (as Speaker and Session Chair), Beijing, China, May 16-20, 2010.
13th Annual Meeting of the Canadian Society of Pharmaceutical Sciences, Vancouver, British Columbia, Canada, June 2-5, 2010.
NIEHS workshop on “Dose-Response Approaches For Nuclear Receptor-Medicated Modes of Action”, Research Triangle Park, NC. September 27-29, 2010.
Center for Molecular Toxicology and Carcinogenesis, Penn State University, University Park, PA. October 13, 2010.
Department of Physiology & Pharmacology and the Interdisciplinary Toxicology Program, University of Georgia, Athens, Georgia. March 28, 2011.
2011 Asia-Pacific ISSX (APISSX) Meeting, Tainan, Taiwan, April 23-25, 2011.
School of Pharmaceutical Sciences, Sun Yat-Sen University. Guangzhou, China. April 27, 2011.
School of Medicine, Sun Yat-Sen University. Guangzhou, China. April 26, 2011.
Beijing Proteome Research Center (BPRC). Beijing, China. June 10, 2011.
School of Public Health, Peking University Health Science Center. Beijing, China. June 15, 2011.
The Third Hospital of the Peking University Health Science Center. Beijing, China. July 4, 2011.
17th North American ISSX Regional Meeting (as Speaker and Session Chair), Atlanta, GA. October 16-20, 2011.
51th Society of Toxicology Annual Meeting, San Francisco, CA. March 11-15, 2012.
Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo. March 28, 2012
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio. April 10, 2012
Experimental Biology 2012 Meeting/ASPET, San Diego, CA. April 21-25, 2012.
Beckman Research Institute, City of Hope, Duarte, California. May 16, 2012
The Third Military Medical University, Chongqing, China. June 11, 2012
School of Medicine, Shantou University, Shantou, Guangdong, China. June 18, 2012
School of Public Health, Sun Yat-Sen University. Guangzhou, China. June 19, 2012
College of Life Science, Beijing Normal University. Beijing, China. June 28, 2012
Penn State Summer Symposium on “Xenobiotic Receptors: Physiological Regulators and Mediators of Toxicity.” State College, PA, July 22-24, 2012.
Laboratory of Reproductive and Developmental Toxicology (LRDT), National Institute of Environmental Health Sciences (NIEHS), NIH, Research Triangle Park, NC. September 7, 2012.
Department of Biochemistry and Molecular Pathology, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio. November 6, 2012.
Gut Homeostasis in Major Chronic Diseases Conference, National Natural Science Foundation of China (NSFC), Shanghai, China. November 12-13, 2012.
Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China. November 13, 2012.