Yanqiao Zhang M.D.
Associate Professor of Integrative Medical Sciences
Adjunct Associate Professor of Pharmaceutical Sciences
Graduate Faculty Advsg Status College of Graduate Studies
Integrative Medical Sciences
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.
Zhang Y, Yin L, Hillgartner FB. 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. 2001 Jan 12;276(2):974-83. PubMed PMID: 11027684.
Zhang Y, Kast-Woelbern HR, Edwards PA. Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. J Biol Chem. 2003 Jan 3;278(1):104-10. Epub 2002 Oct 19. PubMed PMID: 12393883.
Zhang Y, Yin L, Hillgartner FB. SREBP-1 integrates the actions of thyroid hormone, insulin, cAMP, and medium-chain fatty acids on ACCalpha transcription in hepatocytes. J Lipid Res. 2003 Feb;44(2):356-68. Epub 2002 Oct 16. PubMed PMID: 12576518.
Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA. Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes Dev. 2004 Jan 15;18(2):157-69. Epub 2004 Jan 16. PubMed PMID: 14729567; PubMed Central PMCID: PMC324422.
Zhang Y, Hillgartner FB. Starvation and feeding a high-carbohydrate, low-fat diet regulate the expression sterol regulatory element-binding protein-1 in chickens. J Nutr. 2004 Sep;134(9):2205-10. PubMed PMID: 15333705.
Zhang Y, Lee FY, Barrera G, Lee H, Vales C, Gonzalez FJ, Willson TM, Edwards PA. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1006-11. Epub 2006 Jan 12. PubMed PMID: 16410358; PubMed Central PMCID: PMC1347977.
Lee FY, Lee H, Hubbert ML, Edwards PA, Zhang Y. FXR, a multipurpose nuclear receptor. Trends Biochem Sci. 2006 Oct;31(10):572-80. Epub 2006 Aug 14. Review. PubMed PMID: 16908160.
Zhang Y, Wang X, Vales C, Lee FY, Lee H, Lusis AJ, Edwards PA. FXR deficiency causes reduced atherosclerosis in Ldlr-/- mice. Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2316-21. Epub 2006 Jul 6. PubMed PMID: 16825595.
Zhang Y, Edwards PA. FXR signaling in metabolic disease. FEBS Lett. 2008 Jan 9;582(1):10-8. Epub 2007 Nov 20. Review. PubMed PMID: 18023284.
Zhang Y, Yin L, Anderson J, Ma H, Gonzalez FJ, Willson TM, Edwards PA. Identification of novel pathways that control farnesoid X receptor-mediated hypocholesterolemia. J Biol Chem. 2010 Jan 29;285(5):3035-43. doi: 10.1074/jbc.M109.083899. Epub 2009 Dec 7. PubMed PMID: 19996107; PubMed Central PMCID: PMC2823426.
Li T, Chanda D, Zhang Y, Choi HS, Chiang JY. Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes. J Lipid Res. 2010 Apr;51(4):832-42. doi: 10.1194/jlr.M002782. Epub 2009 Oct 28. PubMed PMID: 19965590; PubMed Central PMCID: PMC2842145.
Zhang Y. Farnesoid X receptor-Acting through bile acids to treat metabolic disorders. Drugs Future. 2010 Aug 1;35(8):635-642. PubMed PMID: 24465082; PubMed Central PMCID: PMC3899934.
Lee FY, de Aguiar Vallim TQ, Chong HK, Zhang Y, Liu Y, Jones SA, Osborne TF, Edwards PA. Activation of the farnesoid X receptor provides protection against acetaminophen-induced hepatic toxicity. Mol Endocrinol. 2010 Aug;24(8):1626-36. doi: 10.1210/me.2010-0117. Epub 2010 Jun 23. PubMed PMID: 20573685; PubMed Central PMCID: PMC2940469.
Chong HK, Infante AM, Seo YK, Jeon TI, Zhang Y, Edwards PA, Xie X, Osborne TF. Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1. Nucleic Acids Res. 2010 Oct;38(18):6007-17. doi: 10.1093/nar/gkq397. Epub 2010 May 18. PubMed PMID: 20483916; PubMed Central PMCID: PMC2952856.
Yin L, Ma H, Ge X, Edwards PA, Zhang Y. Hepatic hepatocyte nuclear factor 4α is essential for maintaining triglyceride and cholesterol homeostasis. Arterioscler Thromb
Vasc Biol. 2011 Feb;31(2):328-36. doi: 10.1161/ATVBAHA.110.217828. Epub 2010 Nov 11. PubMed PMID: 21071704; PubMed Central PMCID: PMC3079249.
Ge X, Yin L, Ma H, Li T, Chiang JY, Zhang Y. Aldo-keto reductase 1B7 is a target gene of FXR and regulates lipid and glucose homeostasis. J Lipid Res. 2011 Aug;52(8):1561-8. doi: 10.1194/jlr.M015859. Epub 2011 Jun 5. PubMed PMID: 21642744; PubMed Central PMCID: PMC3137022.
Chen WD, Zhang Y. Regulation of aldo-keto reductases in human diseases. Front Pharmacol. 2012 Mar 9;3:35. doi: 10.3389/fphar.2012.00035. eCollection 2012. PubMed PMID: 22408622; PubMed Central PMCID: PMC3297832.
Zhang Y, Ge X, Heemstra LA, Chen WD, Xu J, Smith JL, Ma H, Kasim N, Edwards PA, Novak CM. Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice. Mol Endocrinol. 2012 Feb;26(2):272-80. doi: 10.1210/me.2011-1157. Epub 2012 Jan 19. PubMed PMID: 22261820; PubMed Central PMCID: PMC3275160.
Cyphert HA, Ge X, Kohan AB, Salati LM, Zhang Y, Hillgartner FB. Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21. J Biol Chem. 2012 Jul 20;287(30):25123-38. doi: 10.1074/jbc.M112.375907. Epub 2012 Jun 1. PubMed PMID: 22661717; PubMed Central PMCID: PMC3408207.
Li Y, Jadhav K, Zhang Y. Bile acid receptors in non-alcoholic fatty liver disease. Biochem Pharmacol. 2013 Dec 1;86(11):1517-24. doi: 10.1016/j.bcp.2013.08.015. Epub 2013 Aug 26. Review. PubMed PMID: 23988487; PubMed Central PMCID: PMC3925679.
Xu J, Yin L, Xu Y, Li Y, Zalzala M, Cheng G, Zhang Y. Hepatic carboxylesterase 1 is induced by glucose and regulates postprandial glucose levels. PLoS One. 2014 Oct 6;9(10):e109663. doi: 10.1371/journal.pone.0109663. eCollection 2014. PubMed PMID: 25285996; PubMed Central PMCID: PMC4186840.
Xu J, Li Y, Chen WD, Xu Y, Yin L, Ge X, Jadhav K, Adorini L, Zhang Y. Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis. Hepatology. 2014 May;59(5):1761-71. doi: 10.1002/hep.26714. Epub 2014 Apr 1. PubMed PMID: 24038130; PubMed Central PMCID: PMC3938573.
Tang Q, Cao B, Lei X, Sun B, Zhang Y, Cheng G. Dextran-peptide hybrid for efficient gene delivery. Langmuir. 2014 May 13;30(18):5202-8. doi: 10.1021/la500905z. Epub 2014 May 1. PubMed PMID: 24786753.
Cao B, Tang Q, Li L, Lee C, Wang H, Zhang Y, Castaneda H, Cheng G. Integrated zwitterionic conjugated poly(carboxybetaine) thiophene) as a new biomaterial platform. Chemical Sciences. 2015 January 01; 6(1):782-788.
Tang Q, Lei X, Cao B, Sun, B., Zhang Y, Cheng G. A naturally derived dextran–peptide vector for microRNA antagomir delivery. RSC advances. 2015 March 23; 5(35):28019-28022.
Xu Y, Zalzala M, Xu J, Li Y, Yin L, Zhang Y. A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism. Nat Commun. 2015 Jun 23;6:7466. doi: 10.1038/ncomms8466. PubMed PMID: 26100857; PubMed Central PMCID: PMC4479415.
Li Y, Zalzala M, Jadhav K, Xu Y, Kasumov T, Yin L, Zhang Y. Carboxylesterase 2 prevents liver steatosis by modulating lipolysis, ER stress and lipogenesis and is regulated by HNF4α. Hepatology. 2016 Jan 25. doi: 10.1002/hep.28472. [Epub ahead of print] PubMed PMID: 26806650.
Xu J, Xu Y, Li Y, Jadhav K, You M, Yin L, Zhang Y. Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4α and Protects Against Alcohol- and MCD diet-induced Liver Injury. Scientific Reports. 2016 Apr 14;6:24277. doi: 10.1038/srep24277. PMID: 27075303.
Xu Y, Li F, Zalzala M, Xu J, Gonzalez FJ, Adorini L, Lee YK, Yin L, Zhang Y. Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice. Hepatology. 2016 Jun 30. doi: 10.1002/hep.28712. [Epub ahead of print]. PMID: 27359351.