Wen Xie (MD, PhD) is Chairman of the Department of Pharmaceutical Sciences, and Joseph Koslow Endowed Professor in Pharmaceutical Sciences at the School of Pharmacy, and Professor of Pharmacology & Chemical Biology at the School of Medicine.
Dr. Xie obtained his MD degree from Peking University Health Science Center, and PhD in Cell Biology from University of Alabama at Birmingham. He completed a postdoctoral fellowship with Dr. Ronald M. Evans at the Salk Institute in La Jolla, California before joining the University of Pittsburgh.
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 responsible for the homeostasis of endogenous chemicals. Therefore, besides drug metabolism and disposition, this regulation has broad implications in many human diseases, including liver diseases (fatty liver, liver fibrosis, liver cancer, and autoimmune hepatitis), endocrine disorders, metabolic syndrome, and cancers. Dr. Xie’s research is conducted using a combination of molecular biology and genetically engineered mice that include tissue and cell type-specific transgenic, knockout and humanized mice.
Dr. Xie is the author or coauthor of more than 200 journal articles and book chapters and he has delivered over 200 invited lectures at conferences and universities. Dr. Xie’s papers have been cited for nearly 14,000 times, and his Scopus H-index is 66 as of 2022. Dr. Xie has edited and published two books: "Nuclear Receptors in Drug Metabolism" (Wiley 2008) and "Drug Metabolism in Diseases" (Elsevier 2016). Dr. Xie has served as ad hoc reviewer for NIH and DOD Study Sections and for over 100 scientific journals.
Among his achievements, Dr. Xie is the recipient of the University of Pittsburgh Chancellor’s Distinguished Research Award, Awards from International Society for the Study of Xenobiotics (ISSX) and American Society for Pharmacology and Experimental Therapeutics (ASPET) Division for Drug Metabolism and Disposition, the Joseph Koslow Endowed Chair in Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy Graduate Program Faculty Member of the Year Award, and National Institute of Environmental Health Sciences (NIEHS) Revolutionizing Innovative, Visionary Environmental health Research (RIVER) R35 Award. Dr. Xie was elected AAAS Fellow in 2022.
Dr. Xie's lab is currently having openings for MS and PhD students, postdoctoral fellows, and visiting students/scholars. All positions are NIH grant funded. Our lab uses combinations of genetically engineered mice, disease models, patient samples, and mechanistic characterizations to dissect organ- and cell type-specific functions of nuclear receptors, nuclear receptor target drug-metabolizing enzymes and transporters, and covalent protein modifications (sulfation and glutathionylation) in liver and gastrointestinal diseases, including liver fibrosis, NAFLD/NASH, liver cancer, IBD, colon cancer, and pancreatic cancer.
Candidates with experience in liver disease, immunology, cancer biology, metabolomics and proteomics are particularly encouraged to apply. Postdocs who exhibit outstanding performance will have the opportunity to advance to faculty position within the Department. Email CV and names of three references to Dr. Wen Xie (wex6@pitt.edu), Chairman and Joseph Koslow Endowed Professor, Center for Pharmacogenetics and Department Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Nuclear receptor-mediated transcriptional regulation of genes that encode drug metabolizing enzymes and drug transporters, and implications of this regulation in xenobiotic and endobiotic homeostasis and human diseases.
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
The Joseph Koslow Endowed Chair in Pharmaceutical Sciences
University of Pittsburgh School of Pharmacy Graduate Program Faculty Member of the Year Award
National Institute of Environmental Health Sciences (NIEHS) Revolutionizing Innovative, Visionary Environmental health Research (RIVER) R35 Award
American Association for the Advancement of Science (AAAS) Fellow"
Since 2015 and representative:
Gastroenterology 157: 793-806 (2019); 161: 271-286 (2021); and 162: 1226-1241 (2022); Cancer Res 80: 4399-4413 (2020);
Sci Adv 7: eabg9241 (2021); Hepatol Commun 4: 1664-1679 (2020); 6: 1123-1139 (2022); Endocrinology 163: bqac061 (2022).
Nat Commun 6:7979 (2015); J Hepatol 64:44-52 (2016); Nat Med. 24:1789-1790 (2018); Hepatology 70:995-1010 (2019);
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 Chem. 290: 14754-14764 (2015)
Hu B, Guo Y, Garbacz WG, Jiang M, Xu M, Huang H, Tsung A, Billiar TR, Ramakrishnan SK, Shah YM, Lam KSL, Huang M, Xie W. Fatty acid binding protein-4 (FABP4) is a hypoxia inducible gene that sensitizes mice to liver ischemia/re-perfusion injury. J Hepatol 63: 855-862 (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)
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. 2016; 64: 44-52
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)
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)
Chen Y, Xia R, Huang Y, Zhao W, Li J, Zhang X, Wang P, Venkataramanan R, Fan J, Xie W, Ma X, Lu B, Li S. An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy. Nat Commun 7: 13443 (2016).
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)
Hu B, Li Y, Gao L, Guo Y, Zhang Y, Chai X, Xu M, Yan J, Lu P, Ren S, Zeng S, Liu Y, Xie W, Huang M. Hepatic induction of fatty acid binding protein 4 (FABP4) plays a pathogenic role in sepsis in mice. Am J Pathol 187: 1059-1067 (2017)
Garbacz WG, Jiang M, Xu M, Yamauchi J, Dong HH, Xie W. Sex- and tissue-specific role of estrogen sulfotransferase in energy homeostasis and insulin sensitivity. Endocrinology 158: 4093-4104 (2017)
Kim YC, Seok S, Byun S, Kong B, Zhang Y, Guo G, Xie W, Ma J, Kemper B, Kemper J. AhR and Shp regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle. Nat Commun 9: 540 (2018)
Bi Y, Shi X, Zhu J, Guan X, Garbacz WG, Huang Y, Gao L, Yan J, Xu M, Ren S, Ren S, Liu Y, Ma X, Li S, Xie W. Regulation of cholesterol sulfotransferase SULT2B1b by HNF4a constitutes a negative feedback control of hepatic gluconeogenesis. Mol Cell Biol 38: e00654-17 (2018)
Wang Z, Yang B, Zhang M, Guo W, Wu Z, Wang Y, Jia L, Li S; Cancer Genome Atlas Research Network, Xie W, Yang D. lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer. Cancer Cell 33: 706-720 (2018)
Garbacz WG, Uppal H, Yan J, Xu M, Ren S, Stolz DB, Huang M, Xie W. Chronic activation of LXR sensitizes mice to high cholesterol diet induced gut toxicity. Mol Pharmacol 94: 1145-1154 (2018)
Bi Y, Jiang M, Guo W, Guan X, Xu M, Ren S, Yang D, Gaikwad NW, Selcer KW, Xie W. Sex-dimorphic and sex hormone-dependent role of steroid sulfatase in adipose inflammation and energy homeostasis. Endocrinology 159: 3365-3377 (2018)
Lu P, Cai X, Guo Y, Xu M, Tian J, Locker J, Xie W. Constitutive activation of the human aryl hydrocarbon receptor in mice promotes hepatocarcinogenesis independent of its coactivator Gadd45b. Toxicol Sci 167: 581-592 (2019)
Guo GL, Xie W. Metformin action through the microbiome and bile acids. Nat Med. 24: 1789-1790 (2018)
Chen L, Liu Q, Tang Q, Kuang J, Li H, Pu S, Wu T, Yang X, Li R, Zhang J, Zhang Z, Huang Y, Li Y, Zou M, Jiang W, Li T, Gong M, Zhang L, Wang H, Qu A, Xie W, He J. Hepatocyte-specific Sirt6 deficiency impairs ketogenesis. J Biol Chem 294: 1579-1589 (2019)
An Y, Wang P, Xu P, Tung HC, Xie Y, Kirisci L, Xu M, Ren S, Tian X, Ma X, Xie W. An unexpected role of cholesterol sulfotransferase and its regulation in sensitizing mice to acetaminophen induced liver injury. Mol Pharmacol 95: 597-605 (2019)
Xie Y, Xu M, Deng M, Li Z, Wang P, Ren S, Guo Y, Ma X, Fan J, Billiar TR, Xie W. Activation of pregnane X receptor sensitizes mice to hemorrhagic shock induced liver injury. Hepatology 70: 995-1010 (2019)
Shehu A, Lu L, Wang P, Zhu J, Wang Y, Yang D, McMahon D, Xie W, Gonzalez FJ, Ma X. Pregnane X receptor activation potentiates ritonavir hepatotoxicity. J Clin Invest 129: 2998-2903 (2019)
Yan J, Tung HC, Li S, Niu Y, Garbacz WG, Lu P, Bi Y, Li Y, He J, Xu M, Ren S, Monga SP, Schwabe RF, Yang D, Xie W. Aryl hydrocarbon receptor signaling prevents activation of hepatic stellate cells and liver fibrogenesis in mice. Gastroenterology 157: 793-806 (2019)
Feng Y, Xie Y, Xu M, Li L, Selcer KW, Oberly PJ, Poloyac SM, Wang H, Li C, Dong F, Yu C, Xie W. Hepatic steroid sulfatase critically determines estrogenic activities of conjugated equine estrogens in human cells in vitro and in mice. J Biol Chem. 294: 12112-12121 (2019)
Wang P, Sachar M, Lu J, Shehu AI, Zhu J, Chen J, Liu K, Anderson KE, Xie W, Gonzalez F J, Klaassen CD, Ma X. The essential role of the transporter ABCG2 in the pathophysiology of erythropoietic protoporphyria. Sci Adv 5: eaaw6127 (2019)
Xie Y, Barbosa AC, Xu M, Oberly PJ, Ren S, Gibbs RB, Poloyac SM, Song W, Fan J, Xie W. Hepatic estrogen sulfotransferase distantly sensitizes mice to hemorrhagic shock-induced acute lung injury. Endocrinology 161: pii: bqz031 (2019)
Barbosa ACS, Zhou D, Xie Y, Choi YJ, Tung HC, Chen X, Xu M, Gibbs RB, Poloyac SM, Liu S, Yu Y, Luo J, Liu Y, Xie W. Inhibition of estrogen sulfotransferase (SULT1E1/EST) ameliorates ischemic acute kidney injury in mice. J Am Soc Nephrology 31: 1496-1508 (2020)
Zhang J, Li Y, Liu Q, Huang Y, Li R, Wu T, Zhang Z, Zhou J, Huang H, Tang Q, Huang C, Zhao Y, Zhang G, Jiang W, Mo L, Zhang J, Xie W, He J. Sirt6 alleviated liver fibrosis by deacetylating conserved lysine 54 on Smad2 in hepatic stellate cells. Hepatology 2020 June 14. Online ahead of print.
Gao L, Li B, Wang J, Shen D, Yang M, Sun R, Tung TC, Xu M, Ren S, Zhang M, Yang D, Lu B, Wang H, Liu Y, Xie W. Activation of liver X receptor α sensitizes mice to T-cell mediated hepatitis. Hepatol Commun 4: 1664-1679 (2020)
Fang Z, Wang Y, Wang Z, Xu M, Ren S, Yang D, Hong M, Xie W. ERINA is an estrogen-responsive lncRNA that drives breast cancer through the E2F1/RB1 pathway. Cancer Res 80: 4399-4413 (2020) PMID: 32826278
Guo W, Wang Y, Yang M, Wang Z, Wang Y, Chaurasia S, Wu Z, Zhang M, Yadav GS, Rathod S, Concha-Benavente F, Fernandez C, Li S, Xie W, Ferris RL, Kammula US, Lu B, Yang D. LincRNA-immunity landscape analysis identifies EPIC1 as a regulator of tumor immune evasion and immunotherapy resistance. Sci Adv 7: eabb3555 (2021) PMID: 33568470
Xu P, Xi Y, Zhu J, Zhang M, Luka Z, Stolz DB, Cai X, Xie Y*, Xu M, Ren S, Huang Z, Yang D, York JD, Ma X, Xie W. Intestinal sulfation is essential to protect against colitis and colonic carcinogenesis. Gastroenterology 161: 271-286 (2021) PMID: 33819483
Xi Y, Li Y, Xu P, Li S, Liu Z, Tung HC, Cai X, Wang J, Huang H, Wang M, Xu M, Ren S, Li S, Zhang M, Lee YJ, Huang L, Yang D, He J, Huang Z, Xie W. The anti-fibrotic drug pirfenidone inhibits liver fibrosis by targeting the small oxidoreductase glutaredoxin-1. Sci Adv 7: eabg9241 (2021) PMID: 34516906
Xie Y, Sun R, Gao L, Guan J, Wang J, Bell A, Zhu J, Zhang M, Xu M, Lu P, Cai X, Ren S, Xu P, Monga SP, Ma X, Yang D, Liu Y, Lu B, Xie W. Chronic activation of LXR alpha sensitizes mice to hepatocellular carcinoma. Hepatol Commun 6: 1123-1139 (2022) PMID: 34981658
Xu P, Xi Y, Wang P, Luka Z, Xu M, Tung H-C, Wang J*, Ren S, Feng D, Gao B, Singhi AD, Monga SP, York JD, Ma X, Huang Z, Xie W. Inhibition of p53 sulfoconjugation prevents oxidative hepatotoxicity and acute liver failure. Gastroenterology 161: 271-286 (2022) PMID: 33819483
Feng Y, Xu D, Cai X, Xu M, Garbacz WG, Ren S, Jurczak MJ, Yu C, Wang H, Xie W. Gestational diabetes sensitizes mice to future metabolic syndrome that can be relieved by activating CAR. Endocrinology. Endocrinology 163:bqac061 (2022). PMID: 35524740.
Wang Y, Zhao Y, Guo W, Yadav GS, Bhaskarla C, Wang Z, Wang X, Li S, Wang Y, Chen Y, Pattarayan D, Xie W, Li S, Lu B, Kammula US, Zhang M, Yang D. Genome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response. Sci Adv 8: eadd0005 (2002) PMID: 36475797
