Yanqiao Zhang, M.D.
Department of Integrative Medical Sciences
College of Medicine
M.D., Wuhan University School of Medicine - 1992
M.S., Wuhan University School of Medicine - 1995
Associate Professor, Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio - 2013-present
Assistant Professor, Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio - 2008-2013
Faculty, School of Biomedical Sciences, Kent State University, Kent Ohio - 2008-present
Assistant Researcher, (equivalent to Research Assistant Professor), Department of Medicine, Division of Cardiology, University of California, Los Angeles, Calif. - 2005-2008
Postdoctoral Research Associate, Department of Medicine, Division of Cardiology, University of California, Los Angeles, Calif. - 2001-2005
Postdoctoral Research Associate, Department of Molecular Pharmacology and Biochemistry, West Virginia University, Morgantown, W.Va. - 1998-2001
Research Associate, Department of Genetic Engineering, Wuhan Institute of Biological Products, Ministry of Public Health, China - 1995-1998
Dysregulation of lipid or glucose metabolism may cause increased incidence of cardiovascular disease, diabetes, obesity and fatty liver disease. My research has been focused on understanding how lipid and glucose homeostasis is maintained under normal and disease conditions, in hoping for uncovering novel therapeutic approaches for treatment of lipid and glucose disorders. There are several projects that are being actively pursued in my lab:
- To investigate the role of nuclear receptors in lipid and glucose metabolism. Nuclear receptors are ligand-activated transcription factors that play important regulatory roles in embryo development and adult physiology. We are particularly interested in farnesoid X receptor (FXR) and hepatocyte nuclear factor 4a (HNF4a) . FXR is a member of the nuclear receptor superfamily and plays an important role in maintaining bile acid, lipid and carbohydrate metabolism. Activation of FXR has been shown to lower the levels of plasma triglycerides and cholesterol, reduce hepatic triglyceride levels, inhibit atherogenesis, and improve insulin sensitivity. Thus, FXR has been considered a therapeutic target for treatment of metabolic disease. Indeed, the data from clinical trials have shown that activation of FXR improves insulin sensitivity and fatty liver disease. HNF4a is also a member of the nuclear receptor superfamily. Mutations in human HNF4a causes maturity-onset diabetes of the young type 1 (MODY1) and lipid disorder. The ongoing research in my laboratory will help address how FXR and HNF4a regulate lipid and glucose metabolism.
- To determine the role of carboxylesterase 1 (CES1) in lipid and glucose metabolism. Carboxylesterase 1 (CES1) is highly expressed in the liver, intestine and macrophages. Previous data have shown that over-expression of CES1 increases cholesterol ester hydrolase activity in macrophages and other cell types, and protects against atherosclerosis. Our data show that CES1 also has triglyceride hydrolase activity and regulates hepatic triglyceride turnover. We are interested in elucidating the role of CES1 in controlling lipid and carbohydrate metabolism in various organs, by using transgenic and knockout mouse models.
- To investigate the role of microRNAs in lipid and glucose metabolism. MicroRNAs (miRNAs) are small (~ 19-22 nucleotides) RNA molecules and post-transcriptional regulators that bind to complementary sequences on target mRNAs, usually resulting in translational repression or target degradation and gene silencing. miRNAs, such as miR-33a, -33b, -122, -103/107, and -34a, have been shown to play an important role in regulating lipid and/or carbohydrate metabolism. Recent data demonstrate that miRNAs are relatively easy for targeting by biochemical approaches. We have identified a few miRNAs that appear to regulate lipid and glucose metabolism. We are in the process of characterizing these miRNAs.
Li, Y., Jadhav, K., and Zhang, Y. 2013. Bile acid receptors in non-alcoholic fatty liver disease. Biochemical Pharmacology, in press.
Xu, J., Li, Y., Chen, W-D, Xu, Y., Yin, L., Ge, X., Jadhav, K., Adorini, L.and Zhang, Y. 2013. Hepatic Carboxylesterase 1 is essential for maintaining normal and farnesoid-X receptor-mediated lipid homeostasis. Hepatology, in press.
Cyphert, H.A., Ge, X., Kohan A.B., Salati, L.M., Zhang, Y., and Hillgartner, F.B. 2012. Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 2. J Biol Chem, 287(30):25123-38. PMID: 2661717
Zhang, Y., Ge, X., Heemstra, L.A., Chen, W.D., Xu, J., Smith, J.L., Ma, H., Kasim, N., Edwards, P.A., Novak, C.M. 2012. Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice. Mol Endocrinol, 26(2):272-80.
Chen, W.D., Zhang, Y. 2012. Regulation of aldo-keto reductases in human diseases. Front Pharmacol, 3:35.
Ge, X., Yin, L., Ma, H., Li, T., Chiang, J.Y.L., and Zhang, Y. 2011. Aldo-keto reductase 1B7 is a target gene of FXR and regulates lipid and glucose metabolism. Journal of Lipid Res, 2011 52(8):1561-8. PMCID: PMC3137022.
Yin, L., Ma, H., Ge, X., Edwards, P.A., and Zhang, Y. 2011. Hepatic HNF4α is essential for maintaining triglyceride and cholesterol homeostasis. Arterioscler Thromb Vasc Biol, 31(2):328-36. PMCID: PMC33079249
Zhang, Y.*, 2010. FXR: acting through bile acids to treat metabolic disorders. Drugs of the Future, 35(8):635-641.
Lee, F.Y., Vallim, T.Q.A., Chong, H.K., Zhang, Y., Liu, Y., Jones, S.A., Osborne, T.F., and Edwards, P.A. 2010. Activation of the farnesoid X receptor provides protection against acetaminophen-induced hepatic toxicity. Mol Endocrinol, 24(8):1626-36. PMID: 20573685.
Chong, H.K., Infante, A.M., Seo, Y.K., Jeon, T.I., Zhang, Y., Edwards, P.A., Xie, X., and Osborne, T.F. 2010. Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1. Nucleic Acids Res, 38(18):6007-17. PMID: 20483916.
Zhang, Y., Yin, L., Anderson, J., Ma, H., Gonzalez, F.J., Willson, T.M., and Edwards, P.A. 2010. Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia. J Biol Chem 285:3035-3043. PMID: 19996107.
Li, T., Chanda, D., Zhang, Y., Choi, H.S., and Chiang, J.Y. 2009. Glucose stimulates cholesterol 7α-hydroxylase gene (CYP7A1) transcription in human hepatocytes. J Lipid Res, 51(4):832-42. PMID: 19965590.
Zhang, Y., Edwards, P.A. 2008. FXR signaling in metabolic disease. FEBS Lett, 582(1):10-8. PMID: 18023284.
Hubbert, M.L., Zhang, Y., Lee, F.Y., and Edwards, P.A. 2007. Regulation of hepatic Insig-2 by the farnesoid X receptor. Mol Endocrinol 21:1359-1369. PMID: 17440045.
Lee, F.Y., Lee, H., Hubbert, M.L., Edwards, P.A., and Zhang, Y. 2006. FXR, a multipurpose nuclear receptor. Trends Biochem Sci 31:572-580. PMID: 16908160.
Zhang, Y., Wang, X., Vales, C., Lee, F.Y., Lee, H., Lusis, A.J., and Edwards, P.A. 2006. FXR deficiency causes reduced atherosclerosis in Ldlr-/- mice. Arterioscler Thromb Vasc Biol 26:2316-2321. PMID: 16825595.
Lee, H., Zhang, Y., Lee, F.Y., Nelson, S.F., Gonzalez, F.J., and Edwards, P.A. 2006. FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine. J Lipid Res 47:201-214. PMID: 16251721.
Zhang, Y., Lee, F.Y., Barrera, G., Lee, H., Vales, C., Gonzalez, F.J., Willson, T.M., and Edwards, P.A. 2006. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A 103:1006-1011. PMID: 16410358.
Anisfeld, A.M., Kast-Woelbern, H.R., Lee, H., Zhang, Y., Lee, F.Y., and Edwards, P.A. 2005. Activation of the nuclear receptor FXR induces fibrinogen expression: a new role for bile acid signaling. J Lipid Res 46:458-468. PMID: 15604525.
Zhang, Y., Castellani, L.W., Sinal, C.J., Gonzalez, F.J., and Edwards, P.A. 2004. Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes Dev 18:157-169. PMID: 14729567.
Zhang, Y. & Hillgartner, F.B. 2004. Starvation and feeding a high-carbohydrate, low-fat diet regulates the expression of sterol regulatory element-binding protein-1 in chickens. J Nutr 134, 2205-10. PMID: 15333705.
Anisfeld, A.M., Kast-Woelbern, H.R., Meyer, M.E., Jones, S.A., Zhang, Y., Williams, K.J., Willson, T. and Edwards, P.A. 2003. Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor. J Biol Chem 278: 20420-8. PMID: 12660231.
Zhang, Y., Kast-Woelbern, H.R. & Edwards, P.A. 2003. Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. J Biol Chem 278, 104-10. PMID: 12393883.
Zhang, Y., Yin, L. & Hillgartner, F.B. 2003. SREBP-1 integrates the actions of thyroid hormone, insulin, cAMP, and medium-chain fatty acids on ACCalpha transcription in hepatocytes. J Lipid Res 44, 356-68. PMID: 12576518.
Yin, L., Zhang, Y. & Hillgartner, F.B. 2002. Sterol regulatory element-binding protein-1 interacts with the nuclear thyroid hormone receptor to enhance acetyl-CoA carboxylase-alpha transcription in hepatocytes. J Biol Chem 277, 19554-65. PMID: 11907029.
Wang, Y., Zhang, Y. & Hillgartner, F.B. 2002. Chicken ovalbumin upstream-promoter transcription factor and E-box-binding proteins enhance thyroid-hormone responsiveness of the malic enzyme gene in avian hepatocytes. Biochem J 361, 391-400. PMID: 11772412.
Zhang, Y., Yin, L. & Hillgartner, F.B. 2001. Thyroid hormone stimulates acetyl-coA carboxylase-alpha transcription in hepatocytes by modulating the composition of nuclear receptor complexes bound to a thyroid hormone response element. J Biol Chem 276, 974-83. PMID: 11027684.
Yin, L., Zhang, Y., Charron, T. & Hillgartner, F.B. 2000. Thyroid hormone, glucagon, and medium-chain fatty acids regulate transcription initiated from promoter 1 and promoter 2 of the acetyl-CoA carboxylase alpha gene in chick embryo hepatocytes. Biochim Biophys Acta 1517, 91-9. PMID: 11118620.
Zhang, Y = Corresponding author
Edwards P.A., and Zhang, Y. 2008. FXR and bile acids: critical modulators of metabolism. In Nuclear Receptors as Molecular Targets for Cardiometabolic and Central Nervous System Diseases. J.L. Junien and B. Staels, editors. IOS press, Amsterdam, Netherland. 43-49.