Jia L. Zhuo, M.D., Ph.D.

Henry Ford Content Links

Biography

• M.D., Internal Medicine, Surgery, Pediatrics, Obstetrics & Gynecology, Guangxi Medical University, Nanning, Guangxi,CHINA 1978-1983
• Ph.D., Renal Physiology & Hypertension, The University of Melbourne, Melbourne, Australia 1986-1990
• Postdoctoral Fellow, Hypertension, Austin & Repatriation Medical Center, The University of Melbourne, Melbourne, Australia 1993-1996
• Sabbatical, Renal Physiology & Hypertension, Tulane University Health Sciences Center, New Orleans, LA, USA 1999-2000

Summary of research interests:  Jia Long (Joe) Zhuo, M.D., Ph.D.
My long-term research interest focuses on the vasoactive hormone angiotensin II and its receptor signal transduction pathways in the kidney in health and angiotensin II-induced hypertension. Angiotensin II is the major effector molecule of the renin-angiotensin system, which plays an important physiological role in maintaining body salt and fluid balance and blood pressure homeostasis in part by stimulating proximal tubular sodium and fluid reabsorption. However, emerging evidence also suggests that increased intracellular production or uptake of circulating and intrarenally formed angiotensin II by proximal tubule cells may contribute to increased sodium retention and tubulo-interstitial injury in hypertension. The general hypothesis to be tested in our laboratory is that circulating and intrarenally formed angiotensin II is taken up by proximal tubule cells through AT1a receptor-mediated endocytosis and that internalized angiotensin II acts as an intracellular hormone to increase the expression of the Na+/H+ exchanger NHE-3 and pro-inflammatory cytokines and growth factors. To test our hypothesis, we use complementary approaches, including proximal tubule cells with or without expression of AT1a and/or AT1b receptors, freshly isolated rat and mouse proximal tubules and intact renal cortical nuclei, AT1a receptor-deficient mice and mice with deficiency of tissue angiotensin-converting enzyme in proximal tubules, in vitro and in vivo adenoviral gene transfer, small interfering RNAs, live cell imaging, intracellular microinjection, Western blot analysis and quantitative and real-time RT-PCR. Our studies may help uncover novel signaling mechanisms by which endocrine and paracrine angiotensin II is taken up by proximal tubule cells to induce intracellular responses by stimulating cytoplasmic and nuclear receptors. This information may also help the development of new strategies or drugs to treat angiotensin II-induced hypertensive renal diseases by blocking intracellular or nuclear actions of angiotensin II.

Awards, Honors and Publications

• Academic Excellence Awards, Guangxi Medical College, China (1979-81)
• Guangxi Government Overseas Research Fellowship (1984-85)
• Overseas Postgraduate Research Scholarship, The University of Melbourne, Australia (1986-89)
• Peter Doherty (named after 1996 Nobel Laureate in Medicine) Australian Postdoctoral Fellowship Award, National Health and Medical Research Council (NHMRC), Australia (1993-96)
• Young Australian Investigator Award, International Society of Hypertension (1994)
• Honorary Professor, Department of Physiology, Guangxi Medical College, China (1995-Present)
• Visiting Assistant Professor, Tulane University School of Medicine, New Orleans, LA (1999-2000)
• Short-listed candidate for Harry Goldblatt Hypertension Research Award, The Council for High Blood Pressure Research, American Heart Association (2002, 2003)

• Member, New York Academy of Sciences, USA (1997-Present)
• Member, AAAS
• International Fellow, Council for High Blood Pressure Research, American Heart Association, USA (2000-Present)
• Member, The American Physiological Society, USA (2001-Present)
• Member, American Society of Hypertension (2004-present)
• Member, American Society of Nephrology (2004-present)
• Member, The Editorial Board of the Journal of Hypertension (International Society of Hypertension and European Society of Hypertension, 2004-2007)
• Temporary Member, NIH/Center For Scientific Review (CSR) Hypertension and Microcirculation Study Section (2008-)
• Temporary Member, NIH/CSR Special Review Panel on Circulation Regulation and Pathophysiology (ZRG1-CVS-F-90S) (2008-)
• Member, American Physiological Society Physiological Genomics Steering Committee (2008-2011)
• Abstract Grader, AHA Scientific Sessions 2008
• Reviewer for >16 scientific journals

• Zhuo, J., P. J. Harris, and S. L. Skinner. Modulation of proximal tubular reabsorption by angiotensin II. Clin. Exp. Pharmacol. Physiol. 13: 227-281, 1986.
• Harris, P.J., S. L. Skinner, and J. Zhuo. The effects of atrial natriuretic peptide and glucagon on proximal glomerulo-tubular balance in anesthetized rats. J. Physiol. (Lond.) 402: 29-44, 1988.
• Zhuo, J., P. J. Harris, and S. L. Skinner. Atrial natriuretic factor modulates proximal glomerulo-tubular balance in anesthetized rats. Hypertension. 14:666-673, 1989.
• Harris, P.J., S. L. Skinner, and J. Zhuo. Haemodynamic and renal tubular responses to low-dose infusion and bolus injection of the peptide ANF in anesthetized rats. J. Physiol. (Lond.) 412: 309-320, 1989.
• Harris, P.J., F. A. O. Mendelsohn, S. L. Skinner, and J. Zhuo. Haemodynamic and renal tubular effects of low doses of endothelin in anesthetized rats. J. Physiol. (Lond.) 433:25-39, 1991.
• Song, K., J. Zhuo, and F. A. O. Mendelsohn. Access of peripherally administered DuP 753 to rat brain angiotensin II receptors. Brit. J. Pharmacol. 104: 771-772, 1991.
• Song, K., J. Zhuo, S.Y. Chai, and F. A. O. Mendelsohn. A new method to localize active renin in tissues by autoradiography: application to dog kidney. Kidney Int. 42:639-646, 1991.
• Zhuo, J., K. Song, P. J. Harris, and F. A. O. Mendelsohn. In vitro autoradiography reveals predominantly AT1 angiotensin II receptors in rat kidney. Renal Physiol. Biochem. 15:231-239, 1992.
• Zhuo, J., D. Thomas, P. J. Harris, and S. L. Skinner. The role of endogenous angiotensin II in the regulation of renal haemodynamics and proximal reabsorption. J. Physiol. (Lond.) 453:1-13, 1992.
• Zhuo, J., D. Alcorn, A. M. Allen, and F.A.O. Mendelsohn. High-resolution localization of angiotensin II receptors in rat renal medulla. Kidney Int. 42:1372-1380, 1992.
• Zhuo, J., D. Alcorn, P. J. Harris, and F. A. O. Mendelsohn. Localization and properties of angiotensin II receptors in rat kidney. Kidney Int. 44(Suppl 42):S-40-S-46, 1993.
• Zhuo, J. and F. A. O. Mendelsohn. Intrarenal angiotensin II receptors. In: The Renin-Angiotensin System: Biochemistry, Pathophysiology and Therapeutics, edited by Robertson JIS, Nicholls MG. Gower Medical Publishing, London and New York. pp 25.1-25.14, 1993.
• Zhuo, J., K. Song, S. Y. Chai, and F. A. O. Mendelsohn. Anatomical localization of components of the renin-angiotensin system in different organs and tissues. In: Inhibition of the Renin-Angiotensin System: Recent Advances; edited by G.A. MacGregor & P.S. Sever. Gardiner-Caldwell Communications (Pacific) Ltd, H.K. pp17-25, 1993.
• Zhuo, J., K. Song, S. Y. Chai, D. MacGregor, and F.A.O. Mendelsohn. Localization of angiotensin II receptors and their subtypes in various tissues. In: Current Advances in ACE Inhibition III, edited by G.A. MacGregor & P.A. Sever. Gardiner-Caldwell Communications Ltd.,U.K. pp87-91, 1993.
• Zhuo, J., K. Song, P. J. Harris, and F. A. O. Mendelsohn. Blockade by intravenous losartan of AT1 angiotensin II receptors in rat brain, kidney and adrenal demonstrated by in vitro autoradiography. Clin. Exp. Pharmacol. Physiol. 21:557-567, 1994.
• Zhuo, J., H. Yamada, A, M. Allen, Y. Sun, and F. A. O. Mendelsohn. Localization and properties of angiotensin converting enzyme and angiotensin II receptors in the heart. In: The Cardiac Renin-Angiotensin System, edited by K. Lindpainter and D. Ganten. Futura Scientific Publishing, New York. pp63-88, 1994.
• Dean, R., J. Zhuo, D. Alcorn, D. Casley, and F. A. O. Mendelsohn,. Cellular distribution of 125I-endothelin-1 binding in the rat kidney following in vivo labelling. Am. J. Physiol. 267: F845-F852, 1994.
• Zhuo, J., D. Alcorn, J. McCausland, D. Casley, and F. A. O. Mendelsohn. In vivo occupancy by angiotensin II subtype 1 receptors in rat renal medullary interstitial cells. Hypertension. 23:838-843, 1994.
• Zhuo, J., D. Alcorn, J. McCausland, and F. A. O. Mendelsohn. Localization and regulation of angiotensin II receptors in renomedullary interstitial cells. Kidney Int. 46:1483-1485, 1994.
• Zhuo, J., D. Alcorn, P. J. Harris, G. P. Aldred, and F. A. O. Mendelsohn. Angiotensin II receptor subtypes in the kidney: distribution and function. Nephrology. 1:511-525, 1995.
• Zhuo, J., A. M. Allen, D. Alcorn, D. MacGregor, G. P. Aldred, and F. A. O. Mendelsohn. The distribution of angiotensin II receptors. In: Hypertension: Pathology, Diagnosis, & Management, Second Edition, edited by J.H. Laragh & B.M. Brenner. Raven Press, New York. pp1739-1762, 1995.
• Zhuo, J., W. Anderson, K. Song, and F. A. O. Mendelsohn. In vitro autoradiographic localization of active renin in the juxtaglomerular apparatus of the dog kidney: effect of dietary sodium intake. Clin. Exp. Pharmacol. Physiol. 23:291-298, 1996.
• Zhuo, J., D. P. MacGregor, and F. A. O. Mendelsohn. Comparative distribution of angiotensin II receptor subtypes in mammalian adrenal glands. In: Vascular, Adrenal and Hypertension, edited by G. P. Vinson & D. C. Anderson. Journal of Endocrinology Pty Ltd, London. Pp53-68, 1996.
• Zhuo, J., D. P. MacGregor, and F. A. O. Mendelsohn. Presence of angiotensin II AT-2 receptors in the adventitia of human kidney vasculature. Clin. Exp. Pharmacol. Physiol. 23 (Suppl 3):S147-S153, 1996.
• Zhuo, J., P. Froomes, D. Casley, J. J. Liu, C. Murone, S. Y. Chai, B. Buxton, and F. A. O. Mendelsohn. Perindopril chronically inhibits angiotensin converting enzyme in both endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease. Circulation. 96:174-182, 1997.
• Zhuo, J., D. Casley, C. Murone, and F. A. O. Mendelsohn. Acute and chronic in vivo inhibition by perindopril of angiotensin converting enzyme in the endothelium and adventitia of large blood vessels and organs in rabbits. J. Cardiovasc. Pharmacol. 29:297-310, 1997.
• Zhuo, J., C. Maric, R. Dean, P. J. Harris, D. Alcorn, and F. A. O. Mendelsohn. Localization and functional properties of angiotensin II AT1 receptors in the kidney: focus on renomedullary interstitial cells. Hypertens. Res. 20:233-250, 1997.
• Dean, R., C. Murone, R. A. Lew, J. Zhuo, D. Casley, W. Muller-Esterl, D. Alcorn, and F. A. O. Mendelsohn. Localization of bradykinin B2 binding sites in rat kidney following chronic ACE inhibitor treatment. Kidney Int. 52: 1261-1270, 1997.
• Zhuo, J., A. M. Allen, and F. A. O. Mendelsohn. Angiotensin receptor mapping in health and diseases. ACE Report 136:1-7, 1998.
• Zhuo, J., R. Dean, C. Maric, P. J. Harris, D. Alcorn, and F. A. O. Mendelsohn. Localization and interactions of vasoactive peptide receptors in renomedullary interstitial cells. Kidney Int. 54:S-22-S-28, 1998.
• Zhuo, J., I. Moller, T. Jenkins, S. Y. Chai, A. M. Allen, and F. A. O. Mendelsohn. Mapping of tissue angiotensin converting enzyme, angiotensin AT1, AT2 and AT4 receptors. J. Hypertens. 16:2027-2037, 1998.
• Zhuo, J., R. Dean, C. Maric, D. Alcorn, P. J. Harris, and F. A. O. Mendelsohn. Localization and roles of angiotensin, endothelin and bradykinin receptors in interstitial cells of the renal medulla. Wenner-Gren Foundation International Symposium: Renin-Angiotensin, edited by Hans Ulfendahl & Mattias Aurell, for The Biochemical Society, Portland Press Ltd, London. pp221-235, 1998.
• Zhuo, J., M. Ohishi, and F. A. O. Mendelsohn. Roles of AT1 and AT2 receptors in the hypertensive Ren-2 gene transgenic rat kidney. Hypertension. 33:347-353, 1999.
• Campbell, D.J., A. Kladis, T. A. Briscoe, and J. Zhuo. Type 2 bradykinin receptor antagonism does not modify kinin or angiotensin peptide levels. Hypertension. 33: 1233-1236, 1999.
• Zhuo, J.L. Renomedullary interstitial cells: a target for endocrine and paracrine actions of vasoactive peptides in the renal medulla. Clin. Exp. Pharmacol. Physiol. 27:465-473, 2000.
• Allen, A.M., J. Zhuo, and F. A. O. Mendelsohn. Localization and function of angiotensin AT1 receptors. Am. J. Hypertens. 13:31S-38S, 2000.
• Harrison-Bernard, L.M., J. Zhuo, H. Kobori, M. Ohishi, and L. G. Navar. Intrarenal AT1 receptor and ACE binding in angiotensin II-induced hypertensive rats. Am. J. Physiol. 282:F19-F25, 2002.
• Zhuo, J.L., J. D. Imig, T. G. Hammond, S. Orengo, E. Benes, and L. G. Navar. Ang II accumulation in rat renal endosomes during Ang II-induced hypertension: role of AT1 receptor. Hypertension. 39:116-121, 2002.
• Zhuo, J.L., M. Ohishi, and F. A. O. Mendelsohn. Perindopril alters vascular ACE, AT1 receptor and nitric oxide synthase expression in patients with coronary artery disease. Hypertension. 39: 634-638, 2002.
• Zhuo, J.L. Angiotensin II type 1 receptors and estrogen status: interactions or dissociation? J. Hypertens. 20:1-3, 2002.
• Zhuo, J.L., F. A. O. Mendelsohn, and M. Ohishi. Can ACE inhibitors promote detrimental vascular effects after percutaneous injury? Hypertension. 40:e4-e5, 2002.
• Zhuo, J.L. Monocyte chemoattractant protein-1: a key mediator of angiotensin II-induced target organ damage in hypertensive heart disease. J. Hypertens. 22: 451-454, 2004.
• Zhuo, J.L. Neuropeptide Y T1128C polymorphism: an independent predictor of hypertensive and cardiovascular diseases? J. Hypertens. 22: 1-3, 2004.
• Li, X.C., Shao, Y., Ohishi, M., Campbell, D.J., and Zhuo, J.L. AT1 receptor-activated signaling mediates angiotensin IV-induced renal cortical vasoconstriction in rats. Am. J. Physiol. Renal Physiol. 290: F1024-F1033, 2006.
• Zhuo, J.L., Li, X.C., Garvin, J.L., Navar, L.G., and Carretero, O.A. Intracellular angiotensin II induces cytosolic Ca2+ mobilization by stimulating intracellular AT1 receptors in proximal tubule cells. Am. J. Physiol. Renal Physiol. 290: F1382-F1390, 2006.
• Li, X.C., Carreteo, O.A., Shao, Y., and Zhuo, J.L. Glucagon receptor-mediated MAP kinase ERK 1/2 phosphorylation in mesangial cells: role of protein kinase A and phospholipase C signaling. Hypertension 47: 580-585, 2006.
• Li, X.C., O.A. Carretero, and J.L. Zhuo.. Cross-talk between angiotensin II and glucagon receptor signaling mediates phosphorylation of mitogen-activated protein kinase ERK 1/2 in rat glomerular mesangial cells. Biochem. Pharmacol. 71: 1711-1719, 2006.
• Zhuo, J.L. Intracrine renin and angiotensin II: a novel role in cardiovascular and renal cellular regulation. J. Hypertens. 24: 1017-1020, 2006.
• Li, X.C., Carretero, O.A., Navar, L.G., and Zhuo, J.L. AT1 receptor-mediated accumulation of extracellular angiotensin II in proximal tubule cells: role of cytoskeleton microtubules and tyrosine phosphatase. Am. J. Physiol. Renal Physiol. 291: F375-F-383,2006.
• Zhuo, J.L., O.A. Carretero, and X.C. Li. Effects of AT1 receptor-mediated endocytosis of extracellular angiotensin II on activation of nuclear factor-?B in proximal tubule cells. Ann. NY Acad. Sci. 1091:336-345, 2006.
• Zhuo, J.L., O.A. Carretero, H. Peng, D. Regoli, W. Neugebauer, and N.-E. Rhaleb. Characterization and localization of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) receptor binding sites using 125I-Hpp-Aca-SDKP in rat cardiac fibroblasts. Am. J. Physiol. Heart Circ Physiol. 292: H984-H993, 2007.
• Riad, A., J.L. Zhuo., H.P. Schltheiss, and C. Tschope. The role of the renal kallikrein-kinin system in diabetic nephropathy. Curr. Opin. Nephrol. Hypertens. 16: 22-26, 2007.
• Li, X.C., L.G. Navar, Y. Shao, and J.L. Zhuo.. Genetic deletion of AT1a receptors attenuates intracellular accumulation of angiotensin II in the kidney of AT1a receptor-deficient mice. Am. J. Physiol. Renal Physiol. 293: F586-F593, 2007.
• Li, X.C. and J.L. Zhuo.. Selective knockdown of AT1 receptors by RNA interference inhibits Val5-angiotensin II endocytosis and NHE-3 expression in immortalized rabbit proximal tubule cells. Am. J. Physiol. Cell Physiol. 293: C367-C378, 2007.
• Li, X.C. and J.L. Zhuo.. Novel insights of intracrine angiotensin II and signaling mechanisms in kidney cells. J. the Renin-Angiotensin-Aldosterone System (JRAAS) 8: 23-33, 2007.
• Li, X.C. and J.L. Zhuo.. Targeting glucagon receptor signaling in treating metabolic syndrome and renal injury in type 2 diabetes: theory versus promise. Clin. Sci. 113: 183-193, 2007.
• Li, X.C. and J.L. Zhuo.. In vivo regulation of AT1 receptor-mediated intracellular uptake of [125I]-Val5-angiotensin II in the kidneys and adrenal glands of AT1a receptor-deficient mice. Am J Physiol Renal Physiol. 294: F293-F302, 2008.
• Li, X.C., T.D. Liao and J.L. Zhuo.. Long-term hyperglucagonemia induces early metabolic and renal phenotypes of type 2 diabetes in mice. Clin Sci (Lond). 2007 Nov 20; [Epub ahead of print]. PMID: 18028036 [PubMed - as supplied by publisher]
• Zhuo, J.L. and X.C. Li. Nuclear factor-?B as a hormonal intracellular signaling molecule: focus on angiotensin II-induced cardiovascular and renal injury. Curr. Opin. Nephrol. Hypertens. 17:37-43, 2008.
• Li, X.C. and J.L. Zhuo.. Intracellular angiotensin II directly induces in vitro transcription of TGF-ß1, MCP-1 and NHE-3 mRNAs in isolated rat renal cortical nuclei via activation of nuclear AT1 receptors. Am. J. Physiol. Cell Physiol. 294: C1034–C1045, 2008.
• Zhuo, J.L. Intrarenal perfusion and angiotensin II levels regulate in vivo angiotensin II type 1 receptor imaging in the kidney. Hypertension. 51:e52, 2008.