Department of Pharmacology & Chemical Biology at the University of Pittsburgh
Wen Xie, MD, PhD
Professor and Joseph Koslow Endowed Chair in Pharmaceutical Sciences
306 Salk Pavilion
Pittsburgh, PA 15213

Email:
wex6@pitt.edu
Phone: 412-648-9941

Fax: 412-648-1664


Education
MD, Peking University Health Science Center (Beijing Medical University), 1991.
PhD (Cell Biology), University of Alabama at Birmingham, 1997.
Postdoctoral Fellow (Nuclear Hormone Receptor), Salk Institute, 1998-2002.


Research Areas
Pharmacology of Cell and Organ Systems
Signal Transduction
Photo of Wen Xie, MD, PhD
Photo provided by Wen Xie.



The research focus of Dr. Xie's laboratory is nuclear hormone receptor-mediated transcriptional regulation of genes that encode drug metabolizing enzymes and transporters. These enzymes and transporters are responsible for the metabolic homeostasis of both foreign chemicals (so-called xenobiotics, such as drugs and carcinogens) and endogenous chemicals (so-called endobiotics, such as steroid hormones, lipids and bile acids).  A typical nuclear receptor contains a DNA-binding domain and a ligand-binding domain (Fig. 1). Nuclear receptors regulate gene expression through their ligand-dependent binding to the promoter regions of the target genes (Fig. 2). This regulation has broad implications in chemical homeostasis and human diseases, including drug metabolism & toxicity, hormonal homeostasis & endocrine disorders, lipid homeostasis, hepatobiliary diseases, diabetes & metabolic syndrome, and cancer. (Fig. 3).

Dr. Xie’s research is conducted using a combination of cell cultures and genetically engineered mice that include transgenic, gene knockout, and humanized mice.  We often combine the genetic mouse models with pharmacological models in which the mice are treated with receptor agonists or antagonists.  The nuclear receptor we are most interested include the pregnane X receptor (PXR), constitutive androstane receptor (CAR), liver X receptor (LXR), farnesoid X receptor (FXR), and aryl hydrocarbon receptor (AhR). 

Dr. Xie has authored over 150 journal articles (H-Index 48 as of 2017) and delivered more than 170 invited lectures at conferences and universities. Dr. Xie has published two books:  "Nuclear Receptors in Drug Metabolism," a Wiley book published in 2008 and "Drug Metabolism in Diseases," an Elsevier book published in 2016. Dr. Xie currently serves as ad hoc reviewer for the NIH and DOD Study Sections and for over 90 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, 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.

 





Important Publications

Niu Y, Xu M, Slagle, BL, Huang H, Li S, Guo GL, SHi G, Qin W, Xie W.. Farnesoid X receptor (FXR) ablation sensitizes mice to hepatitis B virus X protein (HBx)-induced hepatocarcinogenesis. Hepatology 65:893-906, 2017.

Garbacz WG, Lu P, Miller TM, Poloyac SM, Eyre NS, Mayrhofer G, Xu M, Ren S, Xie W. Hepatic overexpression of CD36 improves glycogen homeostasis and attenuates high-fat diet induced hepatic steatosis and insulin resistance. Mol Cell Biol 36:2715-2727, 2016.
Jiang M, Klein M, Zanger UM, Mohammad MK, Cave MC, Gaikwad NW, Dias NJ, Selcer KW, Guo Y, He J, Zhang X, Shen Q, Qin W, Li J, Li S, Xie W. Inflammatory regulation of steroid sulfatase, a novel mechanism to control estrogen homeostasis and inflammation in chronic liver disease. J Hepatol 64:44-52, 2016.  
Gao J, Yan J, Xu M, Ren S, Xie W. CAR suppresses hepatic gluconeogenesis by facilitating the ubiquitination and degradation of PGC1α. Mol Endocrinol 29:1558-1570, 2015. 
Lu P, Yan J, Liu K, Garbacz WG, Wang P, Xu M, Ma X, Xie W. Activation of Aryl Hydrocarbon Receptor Dissociates Fatty Liver from Insulin Resistance by Inducing FGF21. Hepatology 61:1908-1919, 2015.
Guo Y, Hu B, Huang H, Tsung A, Gaikwad N, Xu M, Jiang M, Ren S, Fan J, Billiar TR, Huang M, Xie W. Estrogen sulfotransferase is an oxidative stress responsive gene that gender-specifically affects liver ischemia/reperfusion injury. J Biol Che. 290:14754-14764, 2015.
Chai X, Guo Y, Jiang M, Hu B, Li Z, Fan J, Deng M, Billiar TR, Kucera H, Gaikwad NW, Xu M, Lu P, Yan J, Fu H, Liu Y, Yu L, Huang M, Zeng S, Xie W. Estrogen sulfotransferase ablation sensitizes mice to sepsis. Nat Commun 6:7979, 2015.  
Ihunnah CA, Wada T, Philips BJ, Ravuri SK, Gibbs RB, Kirisci L, Rubin JP, Marra KG, Xie W. Estrogen sulfotransferase (EST/SULT1E1) promotes human adipogenesis. Mol Cell Biol 34:1682-1694, 2014.




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