Wen Xie, MD, PhDChair of Pharmaceutical Sciences, The Joseph Koslow Endowed Chair, Professor, Pharmaceutical Sciences
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 also responsible for the homeostasis of numerous endobiotic molecules. 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 cell cultures and genetically engineered mice that include tissue and cell type-specific transgenic, knockout and humanized mice.
Dr. Xie is the author or coauthor of nearly 190 journal articles and book chapters and he has delivered over 190 invited lectures at conferences and universities. Dr. Xie’s papers have been cited for 10,627 times and his H-index is 55 as of September 2019. Dr. Xie has edited and published two books: "Nuclear Receptors in Drug Metabolism", a book published by Wiley in 2008 and "Drug Metabolism in Diseases", an Elsevier book published in 2016. Dr. Xie has served as ad hoc reviewer for 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, 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.
Orphan nuclear receptor-mediated gene regulation in drug metabolism and human diseases.
Selected recent publications:
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 62: 1876-1887 (2013) PMID: 23349477.
He J, Hu B, Shi X, Weidert ER, Lu P, Xu M, Huang M, Kelley EE, Xie W. Activation of the aryl hydrocarbon receptor sensitizes mice to non-alcoholic steatohepatitis by deactivating the mitochondrial sirtuin deacetylase Sirt3. Mol Cell Biol 33: 2047-2055 (2013) PMID: 23508103
Kittayaruksakul S, Zhao W, Xu M, Ren S, Lu J, Wang J, Downes M, Evans RM, Venkataramanan R, Chatsudthipong V, Xie W. Identification of three novel natural product compounds that activate PXR and CAR and inhibit inflammation. Pharm Res 30: 2199-2208 (2013) PMID: 23896737
Shi X, Cheng Q, Xu L, Yan J, Jiang M, He J, Xu M, Stefanovic-Racic M, Sipula I, O'Doherty RM, Ren S, Xie W. Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting HNF4α. Mol Cell Biol. 34: 485-497 (2014) PMID: 24277929
Jiang M, He J, Kucera H, Gaikwad N, Zhang B, Xu MW, O'Doherty RM, Selcer KW, Xie W. Hepatic over-expression of steroid sulfatase ameliorates mouse models of obesity and type 2 diabetes through sex-specific mechanisms. J Biol Chem. 289: 8086-8097 (2014) PMID: 24497646
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) PMID: 24567372
Ou Z, Jiang M, Hu B, Huang Y, Xu M, Ren S, Li S, Liu S, Xie W, Huang M. Transcriptional Regulation of Human Hydroxysteroid Sulfotransferase SULT2A1 by LXR. Drug Metab Dispos. 42: 1684-1689 (2014). PMID: 25028566
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) PMID: 25614121
Cheng Q, Inaba Y, Lu P, Xu M, He J, Zhao Y, Guo GL, Kuruba R, De La Vega R, Evans RW, Li S, Xie W. Chronic activation of FXR in transgenic mice caused perinatal toxicity and sensitized mice to cholesterol toxicity. Mol Endocrinol 29: 571-582 (2015) PMID: 25719402
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) PMID: 25922074
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) PMID: 26070408
Lu P, Xie W. Reply to Correspondence HEP-15-1008 “AHR-FGF21 dissociation of fatty liver from insulin resistance: a timely matter?” Hepatology 63: 1397-1398 (2016) PMID: 26109100
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) PMID: 26259151
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 PMID: 26220752
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) PMID: 26407237
Guo Y, Hu B, Xie Y, Billiar TR, Sperry JL, Huang M, Xie W. Regulation of drug-metabolizing enzymes by local and systemic liver injuries Expert Opin Drug Metab Toxicol. 12: 245-51 (2016) PMID: 26751558
Zhao Z, Xu D, Li S, He B, Huang Y, Xu M, Ren S, Li S, Wang H, Xie W. Activation of liver X receptor attenuates oleic acid-induced acute respiratory distress syndrome. Am J Pathol. 186: 2614-2622 (2016) PMID: 27520356
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) PMID: 27528620
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). PMID: 27819653
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) PMID: 28102638
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) PMID: 28279656 (¶, co-corresponding authors)
Zheng Z, Zhao Z, Li S, Lu X, Jiang M, Lin J, An Y, Xie Y, Xu M, Shen W, Guo GL, Huang Y, Li S, Zhang X, Xie W. Altenusin, a non-steroidal microbial metabolite, attenuates non-alcoholic fatty liver disease by activating the farnesoid X receptor. Mol Pharmacol 92: 425-436 (2017) PMID: 28739572
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) PMID: 28938414
Choi Y, Zhou D, Barbosa AC, Niu Y, Guan X, Xu M, Ren S, Nolin TD, Liu Y, Xie W. Activation of constitutive androstane receptor ameliorates renal ischemia-reperfusion induced kidney and liver injury. Mol Pharmacol 93: 239-250 (2018)
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) PMID: 29622465
Kong B, Sun R, Huang M, Chow MD, Zhong XB, Xie W, Lee YH, Guo GL. A novel fibroblast growth factor 15 dependent- and bile acid independent-promotion of liver regeneration in mice. Hepatology 68: 1961-1976 (2018)
Evers R, Piquette-Miller M, Polli J, Russel F, Sprowl J, Tohyama K, Ware J, de Wildt S, Xie W, Brouwer K. Disease-associated changes in drug transporters may impact the PK and/or toxicity of drugs: a white paper from the International Transporter Consortium. Clin Pharmacol Ther 104: 900-915 (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 2018 Oct 22 [Epub ahead of print] PMID: 30346592
Guo GL, Xie W. Metformin action through the microbiome and bile acids. Nat Med. 24: 1789-1790 (2018) PMID: 30523325
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 2018 Dec 10[Epub ahead of print] PMID: 30530497
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) PMID: 30944208
Li Y, Pu S, Liu Q, Li R, Zhang J, Wu T, Chen L, Li H, Yang X, Zou M, Xiao J, Xie W¶, He J¶. An integrin-based nanoparticle that targets activated hepatic stellate cells and alleviates liver fibrosis. J Control Release. 2019 Apr 17. [Epub ahead of print] PMID: 31004666 (¶, co-corresponding authors)
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) PMID: 31038762
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) PMID: 31039134
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) PMID: 31170413 (#, co-first authors)
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) PMID: 31217279
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
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
Selected recent invited presentations:
The Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland. Baltimore, Maryland. April 10, 2013
10th International ISSX Meeting. Toronto, Ontario, Canada. September 29-October 3, 2013
2013 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting. San Antonio, Texas. November 10-14, 2013.
School of Pharmacy, The Chinese University of Hong Kong. Hong Kong, China. December 5, 2013
10th Biennial Meeting of Chinese Biological Investigators Society (CBIS), Cancun, Mexico. December 21-24, 2013
53rd Society of Toxicology Annual Meeting, Phoenix, AZ. March 23-27, 2014.
20th Microsomes and Drug Oxidations (MDO) Meeting. Stuttgart, Germany. May 18-22, 2014.
Sino-U.S. Forum on Infectious Diseases and Liver Diseases, Beijing 302 Hospital. Beijing, China. June 9, 2014.
Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’An, China. June 13, 2014.
College of Life Science, Beijing Normal University. Beijing, China. June 18, 2014.
NIEHS Tamburro Liver Symposium (Symposium on Environmental Liver Disease). Louisville, Kentucky. September 11-12, 2014.
Departments of Environmental Medicine & Pharmacology, New York University Langone Medical Center. Tuxedo, NY. November 7, 2014.
Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University. Richmond, Virginia. November 11, 2014
Department of Biological Sciences, Duquesne University, Pittsburgh, PA. February 6, 2015.
Experimental Biology 2014 Meeting/ASPET, Boston, MA. March 28-April 1, 2015.
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China. April 10, 2015.
1st Sunrise Symposium for Drug Metabolism, Pharmacokinetics and Dynamics, Nanjing, China. April 11-13, 2015.
Annual Meeting of the Canadian Society of Pharmaceutical Sciences (CSPS), Toronto, Ontario, May 26-29, 2015
School of Pharmaceutical Sciences, Anhui Medical University. Hefei, China. August 19, 2015.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan. October 28, 2015.
UC Davis Cancer Center, Sacramento, CA. November 12, 2015.
Department of Cancer Biology, the Lerner Research Institute of the Cleveland Clinic. Cleveland, Ohio. November 24, 2015.
2nd Ling-Nan International DMPK Summit Conference. Guangzhou, China. December 4-6, 2015.
Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo. Toledo, Ohio. March 23, 2016.
School of Pharmaceutical Sciences, Peking University Health Science Center. Beijing, China. June 3, 2016.
Department of Biology, South University of Science and Technology of China. Shenzhen, China. June 6, 2016.
11th Biennial Meeting of Chinese Biological Investigators Society (CBIS), Chengdu, China. July 29-August 2, 2016.
Center for Molecular Toxicology and Carcinogenesis, Penn State University, University Park, PA. September 14, 2016
21th Microsomes and Drug Oxidations (MDO) Meeting (Speaker and Session Chair). Davis, CA. October 2-6, 2016.
2016 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting. Denver, Colorado. November 13-17, 2016.
Guangdong Provincial Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. December 8, 2016.
School of Pharmaceutical Sciences, Sun Yat-Sen University. Guangzhou, China. December 8, 2016.
2st Sunrise Symposium for Drug Metabolism, Pharmacokinetics and Dynamics, Xiamen, China. December 9-11, 2016.
School of Basic Medical Sciences, Capital Medical University, Beijing, China. December 14, 2016.
Department of Departments of Biopharmaceutical Sciences, University of Illinois at Chicago College of Pharmacy, Chicago, IL. March 7, 2017.
Gordon Research Conference on Drug Metabolism. Holderness School, Plymouth, New Hampshire. July 9-14. 2017
Department of Hepatology and Gastroenterology, the First Affiliated Hospital of Norman Bethune College of Medicine, Jilin University, Jilin, China. August 1, 2017.
Shenyang DMPK Workshop, Shenyang Pharmaceutical University, Shenyang, Liaoning, China. August 2-4, 2017.
Gordon Research Conference on Cellular & Molecular Mechanisms of Toxicology (Speaker and Session Chair). Proctor Academy, Andover, NH, August 13-18, 2017.
2017 American Association for The Study of Liver Diseases (AASLD) Meeting, Washington DC. October 20-24, 2017
3nd Ling-Nan International DMPK Summit Conference. Guangzhou, China. December 1-3, 2017.
8th Xiamen Winter Symposium on Nuclear Receptors. Xiamen, China. December 8-11, 2017.
Department of Physiology and Pathophysiology, Peking University Health Science Center. Beijing, China. March 23, 2018.
6th Asia Pacific International Society for the Study of Xenobiotics (APISSX Meeting), Hangzhou, China. May 11-14, 2018.
22nd Microsomes and Drug Oxidations (MDO) Meeting. Kanazawa, Japan. October 1-5, 2018.
Joy Goodwin Lectureship Seminar, Auburn University College of Veterinary Medicine. Auburn, Alabama. October 31, 2018