The VICC.ORG Directory of Doctors, Healthcare Providers & Researchers
Ming-Zhi Zhang, M.D.
See also:
Assistant Professor of Medicine
Researcher
Contact Information:
Vanderbilt University Medical Center
S-3206 MCN 2175
Nashville, TN 37232-2372
615-343-1548
Research Description
My research focuses on three main areas:
1) Hormonal regulation of renal physiological and pathophysiologic functions. Specifically, we have investigated the regulation of renal cortical and medullary cyclooxygenase-2 (COX-2) expression by different hormones including elements of the renin-angiotensin system, dopaminergic system, adrenal corticosteroids, vasopressin, and others. We have also investigated the regulation of renal COX-2 by type II 11ß hydroxysteroid dehydrogenase (11ßHSD2) elevation of intracellular glucocorticoids. We are now intensively investigating the interaction between the intrarenal dopaminergic system and the intrarenal renin-angiotensin system using genetically manipulated mice with either elevated or reduced intrarenal dopaminergic activity.
2) 11ßHSD2 and colorectal tumorigenesis. COX-2 expression increases in colorectal tumors. Inhibition of COX-2 activity suppresses colorectal tumorigenesis. Both COX-2 and 11ßHSD2 expression are elevated in colorectal adenomas. Glucocorticoids are potent endogenous 11ßHSD2 inhibitors. Inhibition of 11ßHSD2 activity elevates levels of intracellular glucocorticoids in tumor cells, leading to inhibition of both COX-2 and tumorigenesis.
3) Immunohistochemistry in the kidney, application of image analysis and tissue microarray (TMA) in kidney research.
Publications
- Zhang, MZ, Yao, B, Wang, S, Fan, X, Wu, G, Yang, H, Yin, H, Yang, S, Harris, RC Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice. J Clin Invest, 121(7), 2845-54, 2011.
- Zhang, MZ, Su, Y, Yao, B, Zheng, W, Decaestecker, M, Harris, RC Assessing the application of tissue microarray technology to kidney research. J Histochem Cytochem, 58(5), 413-20, 2010.
- Chen, X, Whiting, C, Borza, C, Hu, W, Mont, S, Bulus, N, Zhang, MZ, Harris, RC, Zent, R, Pozzi, A Integrin alpha1beta1 regulates epidermal growth factor receptor activation by controlling peroxisome proliferator-activated receptor gamma-dependent caveolin-1 expression. Mol Cell Biol, 30(12), 3048-58, 2010.
- He, W, Wang, Y, Zhang, MZ, You, L, Davis, LS, Fan, H, Yang, HC, Fogo, AB, Zent, R, Harris, RC, Breyer, MD, Hao, CM Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest, 120(4), 1056-68, 2010.
- Zhang, MZ, Xu, J, Yao, B, Yin, H, Cai, Q, Shrubsole, MJ, Chen, X, Kon, V, Zheng, W, Pozzi, A, Harris, RC Inhibition of 11beta-hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans. J Clin Invest, 119(4), 876-85, 2009.
- Yao, B, Harris, RC, Zhang, MZ Intrarenal dopamine attenuates deoxycorticosterone acetate/high salt-induced blood pressure elevation in part through activation of a medullary cyclooxygenase 2 pathway. Hypertension, 54(5), 1077-83, 2009.
- Zhang, MZ, Yao, B, Fang, X, Wang, S, Smith, JP, Harris, RC Intrarenal dopaminergic system regulates renin expression. Hypertension, 53(3), 564-70, 2009.
- Yao, B, Xu, J, Harris, RC, Zhang, MZ Renal localization and regulation of 15-hydroxyprostaglandin dehydrogenase. Am J Physiol Renal Physiol, 294(2), F433-9, 2008.
- Xu, J, Yao, B, Fan, X, Langworthy, MM, Zhang, MZ, Harris, RC Characterization of a putative intrarenal serotonergic system. Am J Physiol Renal Physiol, 293(5), F1468-75, 2007.
- Zeng, F, Zhang, MZ, Singh, AB, Zent, R, Harris, RC ErbB4 isoforms selectively regulate growth factor induced Madin-Darby canine kidney cell tubulogenesis. Mol Biol Cell, 18(11), 4446-56, 2007.
- Cheng, H, Wang, S, Jo, YI, Hao, CM, Zhang, M, Fan, X, Kennedy, C, Breyer, MD, Moeckel, GW, Harris, RC Overexpression of cyclooxygenase-2 predisposes to podocyte injury. J Am Soc Nephrol, 18(2), 551-9, 2007.
- Zhao, HJ, Wang, S, Cheng, H, Zhang, MZ, Takahashi, T, Fogo, AB, Breyer, MD, Harris, RC Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice. J Am Soc Nephrol, 17(10), 2664-9, 2006.
- Zhang, MZ, Yao, B, Cheng, HF, Wang, SW, Inagami, T, Harris, RC Renal cortical cyclooxygenase 2 expression is differentially regulated by angiotensin II AT(1) and AT(2) receptors. Proc Natl Acad Sci U S A, 103(43), 16045-50, 2006.
- Yao, B, Xu, J, Qi, Z, Harris, RC, Zhang, MZ Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake. Am J Physiol Renal Physiol, 291(2), F368-74, 2006.
- Zhang, MZ, Yao, B, McKanna, JA, Harris, RC Cross talk between the intrarenal dopaminergic and cyclooxygenase-2 systems. Am J Physiol Renal Physiol, 288(4), F840-5, 2005.
- Cheng, H, Zhang, M, Moeckel, GW, Zhao, Y, Wang, S, Qi, Z, Breyer, MD, Harris, RC Expression of mediators of renal injury in the remnant kidney of ROP mice is attenuated by cyclooxygenase-2 inhibition. Nephron Exp Nephrol, 101(3), e75-85, 2005.
- Yao, B, Harris, RC, Zhang, MZ Interactions between 11beta-hydroxysteroid dehydrogenase and COX-2 in kidney. Am J Physiol Regul Integr Comp Physiol, 288(6), R1767-73, 2005.
- Rao, R, Zhang, MZ, Zhao, M, Cai, H, Harris, RC, Breyer, MD, Hao, CM Lithium treatment inhibits renal GSK-3 activity and promotes cyclooxygenase 2-dependent polyuria. Am J Physiol Renal Physiol, 288(4), F642-9, 2005.
- Cheng, HF, Zhang, MZ, Harris, RC NITRIC OXIDE STIMULATES CYCLOOXYGENASE-2 IN CULTURED CTAL CELLS THROUGH A P38-DEPENDENT PATHWAY. Am J Physiol Renal Physiol, 2005.
- Harris, RC, Zhang, MZ, Cheng, HF Cyclooxygenase-2 and the renal renin-angiotensin system. Acta Physiol Scand, 181(4), 543-7, 2004.
- Schneider, A, Zhang, Y, Zhang, M, Lu, WJ, Rao, R, Fan, X, Redha, R, Davis, L, Breyer, RM, Harris, R, Guan, Y, Breyer, MD Membrane-associated PGE synthase-1 (mPGES-1) is coexpressed with both COX-1 and COX-2 in the kidney. Kidney Int, 65(4), 1205-13, 2004.
- Zhang, MZ, Mai, W, Li, C, Cho, SY, Hao, C, Moeckel, G, Zhao, R, Kim, I, Wang, J, Xiong, H, Wang, H, Sato, Y, Wu, Y, Nakanuma, Y, Lilova, M, Pei, Y, Harris, RC, Li, S, Coffey, RJ, Sun, L, Wu, D, Chen, XZ, Breyer, MD, Zhao, ZJ, McKanna, JA, Wu, G PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells. Proc Natl Acad Sci U S A, 101(8), 2311-6, 2004.
- Zhang, MZ, Sanchez Lopez, P, McKanna, JA, Harris, RC Regulation of cyclooxygenase expression by vasopressin in rat renal medulla. Endocrinology, 145(3), 1402-9, 2004.
- Zhang, MZ, Wang, SW, Cheng, H, Zhang, Y, McKanna, JA, Harris, RC Regulation of renal cortical cyclooxygenase-2 in young rats. Am J Physiol Renal Physiol, 285(5), F881-8, 2003.
- Cheng, HF, Wang, CJ, Moeckel, GW, Zhang, MZ, McKanna, JA, Harris, RC Cyclooxygenase-2 inhibitor blocks expression of mediators of renal injury in a model of diabetes and hypertension. Kidney Int, 62(3), 929-39, 2002.
- Zhang, MZ, Hao, CM, Breyer, MD, Harris, RC, McKanna, JA Mineralocorticoid regulation of cyclooxygenase-2 expression in rat renal medulla. Am J Physiol Renal Physiol, 283(3), F509-16, 2002.
- Cheng, HF, Wang, SW, Zhang, MZ, McKanna, JA, Breyer, R, Harris, RC Prostaglandins that increase renin production in response to ACE inhibition are not derived from cyclooxygenase-1. Am J Physiol Regul Integr Comp Physiol, 283(3), R638-46, 2002.
- Cheng, HF, Wang, JL, Zhang, MZ, Wang, SW, McKanna, JA, Harris, RC Genetic deletion of COX-2 prevents increased renin expression in response to ACE inhibition. Am J Physiol Renal Physiol, 280(3), F449-56, 2001.
- Harris, RC, Cheng, H, Wang, J, Zhang, M, McKanna, JA Interactions of the renin-angiotensin system and neuronal nitric oxide synthase in regulation of cyclooxygenase-2 in the macula densa. Acta Physiol Scand, 168(1), 47-51, 2000.
- Cheng, HF, Wang, JL, Zhang, MZ, McKanna, JA, Harris, RC Nitric oxide regulates renal cortical cyclooxygenase-2 expression. Am J Physiol Renal Physiol, 279(1), F122-9, 2000.
- Cheng, HF, Wang, JL, Zhang, MZ, McKanna, JA, Harris, RC Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride. J Clin Invest, 106(5), 681-8, 2000.
- Cheng, HF, Wang, JL, Zhang, MZ, Miyazaki, Y, Ichikawa, I, McKanna, JA, Harris, RC Angiotensin II attenuates renal cortical cyclooxygenase-2 expression. J Clin Invest, 103(7), 953-61, 1999.
- Zhang, MC, He, L, Giro, M, Yong, SL, Tiller, GE, Davidson, JM Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN). J Biol Chem, 274(2), 981-6, 1999.
- Zhang, MZ, Harris, RC, McKanna, JA Regulation of cyclooxygenase-2 (COX-2) in rat renal cortex by adrenal glucocorticoids and mineralocorticoids. Proc Natl Acad Sci U S A, 96(26), 15280-5, 1999.
- McKanna, JA, Zhang, MZ, Wang, JL, Cheng, H, Harris, RC Constitutive expression of cyclooxygenase-2 in rat vas deferens. Am J Physiol, 275(1 Pt 2), R227-33, 1998.
- Harris, RC, Wang, JL, Cheng, HF, Zhang, MZ, McKanna, JA Prostaglandins in macula densa function. Kidney Int Suppl, 67S49-52, 1998.
- Wang, JL, Cheng, HF, Zhang, MZ, McKanna, JA, Harris, RC Selective increase of cyclooxygenase-2 expression in a model of renal ablation. Am J Physiol, 275(4 Pt 2), F613-22, 1998.
- Zhang, MZ, Wang, JL, Cheng, HF, Harris, RC, McKanna, JA Cyclooxygenase-2 in rat nephron development. Am J Physiol, 273(6 Pt 2), F994-1002, 1997.
- Zhang, MZ, McKanna, JA Gliogenesis in postnatal rat optic nerve: LC1 + microglia and S100-beta + astrocytes. Brain Res Dev Brain Res, 101(1-2), 27-36, 1997.
- McKanna, JA, Zhang, MZ Immunohistochemical localization of lipocortin 1 in rat brain is sensitive to pH, freezing, and dehydration. J Histochem Cytochem, 45(4), 527-38, 1997.
- Melzer, P, Zhang, MZ, McKanna, JA Infraorbital nerve transection and whisker follicle removal in adult rats affect microglia and astrocytes in the trigeminal brainstem. A study with lipocortin1- and S100beta-immunohistochemistry. Neuroscience, 80(2), 459-72, 1997.
- Sakai, M, Zhang, M, Homma, T, Garrick, B, Abraham, JA, McKanna, JA, Harris, RC Production of heparin binding epidermal growth factor-like growth factor in the early phase of regeneration after acute renal injury. Isolation and localization of bioactive molecules. J Clin Invest, 99(9), 2128-38, 1997.
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