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Ya-Xiong Tao, PhD

Professor of Physiology, joined the College of Veterinary Medicine in 2004. He obtained his PhD from the Institute of Zoology, Chinese Academy of Sciences, Beijing, China.  He did post-doctoral training at the University of Louisville with Dr. Ch. V. Rao and at the University of Iowa with Dr. Deborah L. Segaloff.  He was Assistant Research Scientist at the Department of Physiology and Biophysics at the University of Iowa Carver College of Medicine before coming to Auburn.

Research Interests

Research Interests:  Research in the lab is directed to elucidate the structure-function relationships of G protein-coupled receptors, especially the neural melanocortin receptors, melanocortin-3 and -4 receptors.  These receptors are critically involved in the regulation of energy homeostasis.  Naturally occurring mutations in the genes for these receptors have been identified from obese patients.  Our current focus is two fold: 1. The molecular defects of the naturally occurring mutations identified from obese patients in these receptors and potential ways to correct these defects; 2. The molecular mechanisms of ligand binding and receptor activation including biased signaling.  A multi-disciplinary approach, including pharmacological, biochemical, molecular biological, and cell biological techniques, as well as computer modeling, is used for these studies.

Selected Publications

He S and Tao Y-X. Defect in MAPK signaling as a cause for monogenic obesity caused by inactivating mutations in the melanocortin-4 receptor gene. Int. J. Biol. Sci. 10:1128-1137, 2014.

Huang H and Tao Y-X. Functions of the DRY motif and intracellular loop 2 of human melanocortin 3 receptor. J. Mol. Endocrinol. 53:319-330, 2014.

Tao Y-X and Huang H. Ipsen 5i acts as a pharmacological chaperone and rescues the intracellularly retained melanocortin-4 receptor mutants. Front Endocrinol. 5:131, 2014.

Huang H and Tao Y-X. A small molecule agonist THIQ as a novel pharmacoperone for intracellularly retained melanocortin-4 receptor mutants. Int. J. Biol. Sci. 10:817-824, 2014.

Tao Y-X and Conn PM.  Chaperoning G-protein coupled receptors: From cell biology to therapeutics. Endocr. Rev. 35:602-647, 2014.

Tao Y-X. Constitutive activity in melanocortin-4 receptor: Biased signaling of inverse agonists. Adv. Pharmacol. 70:135-154, 2014.

Bhushan S, Kondo K, Polhemus D, Nicholson C, Tao Y-X, Huang H, Georgiopoulou VV, Murohara T, Calvert JW, Butler J, and Lefer DJ. Nitrite therapy improves left ventricular function during heart failure via restoration of nitric oxide and nitrosothiol mediated cytoprotective signaling. Circ. Res. 114:1281-1292, 2014.

Hohenadel MG, Thearle MS, Grice BA, Huang H, Dai MH, Tao Y-X, Hunter LA, Palaguachi GI, Mou ZY, Kim RC, Tsang MM, Haack K, Voruganti VS, Cole SA, Butte NF, Comuzzie AG, Muller YL, Baier LJ, Krakoff J, Knowler WC, Yanovski JA and Han JC. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants. Int. J. Obes. 38:1068-1074, 2014.

King AL, Polhemus DJ, Bhushan S, Otsuka H, Kondo K, Nicholson C, Bradley JM, Islam KN, Calvert JW, Tao Y-X, Dugas TR, Kelley EE, Elrod JW, Wang R and Lefer DJ. Endothelial nitric oxide synthase (eNOS) regulation by cystathione gamma lyase (CSE): Crosstalk between hydrogen sulfide (H2S) and nitric oxide (NO) signaling pathways. Proc. Natl. Acad. Sci. USA 111:3182-3197, 2014.

Fang L, Liang XF, Zhou Y, Guo XZ, He Y, Yi TL, Liu LW, Yuan XC and Tao Y-X. Programming effects of high carbohydrate feeding of larvae on adult glucose metabolism in zebrafish, Danio rerio. Brit J Nutri 111:808-818, 2014.

Tao Y-X and Liang XF.  G protein-coupled receptors as regulators of glucose homeostasis and therapeutic targets for diabetes mellitus. Prog. Mol. Biol. Transl. Sci. 121:1-21, 2014.

Huang H, Dai MH and Tao Y-X. Physiology and therapeutics of the free fatty acid receptor GPR40. Prog. Mol. Biol. Transl. Sci. 121:67-94, 2014.

Mo XL, Yang Z & Tao Y-X. Targeting GPR119 for the potential treatment of type 2 diabetes mellitus and obesity. Prog. Mol. Biol. Transl. Sci. 121:95-131, 2014.

He S, Liang X-F, Li L, Huang W, Shen D and Tao Y-X. Gene structure and expression of leptin in Chinese perch. Gen. Comp. Endocrinol. 194:183-188, 2013.

He S, Liang X-F, Sun J, Li L, Yu Y, Huang W, Qu C-M, Cao L, Bai X-L and Tao Y-X. Insights into food preference in hybrid F1 of Siniperca chuatsi (♀) x Siniperca scherzeri (♂) mandarin fish through transcriptome analysis. BMC Genomics 14:601, 2013.

Mo X-L and Tao Y-X. Activation of mitogen-activated protein kinase by inverse agonists in six naturally occurring constitutively active mutant human melanocortin-4 receptor. Biochim. Biophys. Acta 1832:1939-1948, 2013.

Wei HK, Zhou YF, Jiang SZ, Tao Y-X, Sun HQ, Peng J and Jiang SW.  DHA-enriched diet increases skeletal muscle protein synthesis in growing pigs:  Association with increased skeletal muscle insulin action and IGF-1 expression.  Brit J Nutri 110:671-680, 2013.

Wang ZQ and Tao Y-X. Functions of the third intracellular loop of the human melanocortin-3 receptor. Curr Pharm Des 19:4831-4838, 2013.

Tao Y-X, Yuan ZH and Xie J.  G protein-coupled receptors as regulators of energy homeostasis.  Prog Mol Biol Transi Sci 114:1-43, 2013.

Mo XL, Wei HK, Peng J and Tao Y-X.  Free fatty acid receptor GPR120 and pathogenesis of obesity and type 2 diabetes mellitus.  Prog Mol Biol Transi Sci 114:251-276, 2013.

Huang H and Tao Y-X.  Pleiotropic functions of the transmembrane domain 6 of human melanocortin-4 receptor. J Mol Endocrinol 49:237-248, 2012. 

Mo XL, Yang R and Tao Y-X.  Functions of transmembrane domain 3 of human melanocortin-4 receptor. J Mol Endocrinol 49:221-235, 2012.

Hafiz S, Dennis J, Schwartz D, Judd R, Tao Y-X, Khazal K, Akingbemi B, Mo XL, Abdel-Mageed AB, Morrison EE and Mansour M. Expression of melanocortin receptors in human prostate cancer cell lines: MC2R activation by ACTH increases prostate cancer cell proliferation.  Int J Oncol 41:1373-1380, 2012.

Yang F and Tao Y-X. Functional characterization of nine novel naturally occurring mutations in human melanocortin-3 receptor. Biochim Biophys Acta – Molecular Basis of Disease 1822:1752-1761, 2012.

Bhushan S, Kondo K, Predmore BL, Zlatopolsky M, King AL, Pearce C, Huang H, Tao Y-X, Condit ME and Lefer DJ. Selective ß2-adrenoreceptor stimulation attenuates myocardial cell death and preserves cardiac function following ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 32:1865-1874, 2012.

Wang ZQ and Tao YX. Functional studies on twenty novel naturally occurring melanocortin-4 receptor mutations. Biochim. Biophys. Acta 1812:1190-1199, 2011.

Yan J and Tao Y-X.  Pharmacological characterization of canine melancortin-4 receptor and its natural variant V213F. Domest Anim Endocrinol 41:91-97, 2011.

Tao YX.  Mutations in the melanocortin-3 receptor (MC3R) gene: Impact on human obesity or adiposity.  Curr Opin Invest Drugs 11:1092-1096, 2010.

Tao Y-X, Huang H, Wang Z-Q, Yang F, Williams JN, Nikiforovich GV. Constitutive activity of neural melanocortin receptors. Methods Enzymol 484:267-279, 2010.

Tao YX. The melanocortin-4 receptor: Physiology, pharmacology and pathophysiology. Endocrine Reviews 31:506-543, 2010.

Mansour M, White D, Wernette C, Dennis J, Tao Y-X, Collins R, Parker L, Morrison E. Pancreatic neuronal melanocortin-4 receptor modulates serum insulin levels independent of leptin receptor.  Endocrine 37:220-230, 2010

Fan Z-C, Tao Y-X. Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients. J Cell Mol Med 13:3268-3282, 2009.

Tao Y-X, Segaloff DL. Follicle stimulating hormone receptor mutations and reproductive disorders. Prog Mol Biol Transl Sci 89:115-131, 2009.

Roth CL, Ludwig M, Woelfle J, Fan Z-C, Brumm H, Biebermann H, Tao Y-X. A novel melanocortin-4 receptor gene mutation in a female patient with severe childhood obesity. Endocrine 36:52-59, 2009.

Tao Y-X. Mutations in melanocortin-4 receptor and human obesity. Prog Mol Biol Transl Sci 88:173-204, 2009.

Hancock KD, Coleman ES, Tao Y-X, Morrison EE, Braden TD, Kemppainen BW, Akingbemi BT. Genistein decreases androgen biosynthesis in rat Leydig cells by interference with luteinizing hormone-dependent signaling. Toxicol Lett 184:169-175, 2009.

Tao Y-XConstitutive activation of G protein-coupled receptors and diseases: insights into mechanism of activation and therapeutics. Pharmacology and Therapeutics 120:129-148, 2008.

Wang S-X, Fan Z-C, Tao Y-XFunctions of acidic transmembrane residues in human melanocortin-3 receptor binding and activation. Biochem Pharmacol 76:520-530, 2008.

Fan ZC, Sartin JL, Tao YXPharmacological analyses of two naturally occurring porcine melanocortin-4 receptor mutations in domestic pigs. Domest Anim Endocrinol 34:383-390, 2008.

Fan Z-C, Sartin JL, Tao Y-XMolecular cloning and pharmacological characterization of porcine melanocortin-3 receptor. J Endocrinol 196:139-148, 2008.

Tao Y-X. Inactivating melanocortin-4 receptor mutations and human obesity.  In Obesity and Energy Metabolism: Research and Clinical Applications, Donohoue PA, Editor. Humana Press, Totowa, NJ. Pages 45-58, 2008.

Tao Y-XFunctional characterization of novel melanocortin-3 receptor mutations identified from obese subjects. Biochimica et Biophysica Acta - Molecular Basis of Disease 1772:1167-1174, 2007.

Zhang M, Tao Y-X, Ryan GL, Feng X, Fanelli F, Segaloff DL. Intrinsic differences in the response of the human lutropin receptor versus the human follitropin receptor to activating mutations. J Biol Chem 282(35):25527-25539, 2007.

Freitas KCM, Ryan G, Brito VN, Tao Y-X, Costa EMF, Mendonca BB, Segaloff D, Latronico AC. Molecular analysis of the neuropeptide Y1 receptor gene in human idiopathic gonadotropin-dependent precocious puberty and isolated hypogonadotropic hypogonadism. Fertility and Sterility 87(3):627-634, 2007. 

Tao Y-XInactivating mutations of G protein-coupled receptors and diseases: structure-function insights and therapeutic implications. Pharmacology and Therapeutics 111:949-973, 2006.

Rong R, Tao Y-X, Cheung BMY, Xu A, Cheung GCN, Lam KSL. Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population. Clin Endocrinol 65:198-205, 2006.

Tao Y-X, Segaloff DL. Functional analyses of melanocortin-4 receptor mutations identified from patients with binge eating disorder and non-obese or obese subjects. J Clin Endocrinol Metab 90:5632-5638, 2005.

Tao Y-XMolecular mechanisms of the neural melanocortin receptor dysfunction in severe early-onset obesity. Mol Cell Endocrinol 239:1-14, 2005.

Tao Y-X, Segaloff DL. Functional characterization of melanocortin-3 receptor variants identify a loss-of-function mutation involving an amino acid critical for G protein-coupled receptor activation. J Clin Endocrinol Metab 89:3936-3942, 2004.

Tao Y-X, Johnson NB, Segaloff DL. Constitutive and agonist-dependent self-association of the cell surface human lutropin receptor. J Biol Chem 279:5904-5914, 2004.

Donohoue PA, Tao Y-X, Collins M, Yeo GSH, O’Rahilly S, Segaloff DL. Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female. J Clin Endocrinol Metab 88:5841-5845, 2003.

Tao Y-X, Segaloff DL. Functional characterization of human melanocortin-4 receptor mutations associated with childhood obesity. Endocrinology 144:4544-4551, 2003.

Shinozaki H, Butnev V, Tao Y-X, Ang KL, Conti M, Segaloff DL. Desensitization of Gs-coupled receptor signaling by constitutively active mutants of the human lutropin/choriogonadotropin receptor. J Clin Endocrinol Metab 88:1194-1204, 2003.

Tao Y-X, Mizrachi D, Segaloff DL. Chimeras of the rat and human FSH receptors (FSHRs) identify residues that permit or suppress transmembrane 6 mutation-induced constitutive activation of the FSHR via rearrangements of hydrophobic interactions between helices 6 and 7. Mol Endocrinol 16:1881-1892, 2002.

Tao Y-X, Abell AN, Liu X, Nakamura K, Segaloff DL. Constitutive activation of G protein-coupled receptors as a result of substitution of a conserved leucine residue in transmembrane helix III.  Mol Endocrinol 14:1272-1282, 2000. 

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