Wen Xie, MD, PhD

Wen Xie, MD, PhD*

Center for Pharmacogenetics
306 Salk Pavilion
Pittsburgh, PA 15261


Liver-Related Work

Research Interests: My research interest is nuclear receptor-mediated gene regulation in liver metabolism and liver diseases.  We are interested in the regulation of genes that encode drug metabolizing enzymes and transporters.  In addition to metabolizing drugs, the same enzyme and transporter systems are also responsible for the homeostasis of endogenous chemicals that include steroid hormones, cholesterol, lipids, glucose, bile acids, and bilirubin. As such, the nuclear receptor-mediated regulatory network is implicated in both drug metabolism and many pathophysiological conditions, including liver diseases such as fatty liver and cholestasis.  Moreover, nuclear receptors represent potential therapeutic targets for the treatment and prevention of many human diseases, such as gastrointestinal diseases, metabolic syndrome, endocrine disorders, breast cancer, prostate cancer, and colon cancer.  Besides nuclear receptors, my lab is also interested to study the effects of hepatic sulfotransferases and aryl hydrocarbon receptor (AhR) on energy metabolism and metabolic disease.  
Ongoing Research Studies:
  1. A Novel Regulation of the Phase II Enzyme Estrogen Sulfotransferase in the Liver. The goal of this study is to determine the inflammatory regulation of the hepatic estrogen sulfotransferase (EST) and the implications of this regulation in sepsis response. This study is a collaboration with Dr. Timothy Billiar from the Department of Surgery and Dr. Jie Fan from the Surgical Research, Veterans Affairs Pittsburgh Healthcare System.
  2. The Hepatic Function of Cholesterol Sulfotransferase 2B1b (SULT2B1b) in Energy Metabolism. The goal of this project is to study the role of cholesterol sulfotransferase 2B1b (SULT2B1b) and its enzymatic byproduct cholesterol sulfate in glucose metabolism and metabolic disease. The focus is the effect of SULT2B1b on hepatic gluconeogenesis. This study is a collaboration with Dr. Robert M. O’Doherty from the Division of Endocrinology and Metabolism, Department of Medicine.
  3. The Perinatal Pharmacology of the Nuclear Receptor FXR. The goal of this project is to study the perinatal maternal and fetal effect of FXR activation in the liver. Our hypothesis is that chronic activation of FXR during neonatal development may have a unique effect on liver by regulating the homeostasis of bile acids and lipophilic nutrients. This study is a collaboration with Dr. Song Li from the Department of Pharmaceutical Sciences and Dr. Rhob Evans from the Department of Epidemiology.
  4. A Novel Role of the Aryl Hydrocarbon Receptor in Hepatic Steatosis. The goal of this project is to study the role of the aryl hydrocarbon receptor (AhR) in fatty liver, as well as the disassociation of fatty and insulin resistance through the transcriptional regulation of FGF21 by AhR in the liver.
Research Service: My lab and faculty colleagues at the Center for Pharmacogenetics are experienced in the creation and characterization of transgenic and knockout mice, integration of mouse genetic models with liver disease models, and characterization of disease phenotypes at the molecular and biochemical levels. For details please contact me at the address above.

 

The Joseph Koslow Endowed Chair, Professor
Department of Pharmaceutical Sciences
Team Leader, Chronic Liver Diseases SIG