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  • Jia L. Zhuo, MD, PhD

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    Professor
    Office: G323
    Phone: (601) 984-1707
    Fax: (601) 984-1637
    E-mail: jzhuo@umc.edu

    View NIH biosketch

    Research interests

    • Angiotensin II receptor pharmacology and signal transduction
    • Roles of NHE3 in the proximal tubule in pressure natriuresis
    • Hypertension

    Current research

    Data included in AJP cover article, May 2012 (doi: 10.1152/ajpregu.00487.2011)
    Data included in AJP cover article, May 2012 (doi: 10.1152/ajpregu.00487.2011)

    My laboratory is interested in the roles of endocrine (tissue-to-tissue), paracrine (cell-to-cell), and intracrine (cytoplasmic and nuclear) angiotensin II (ANG II) and its G protein-coupled receptor (GPCR) signal transduction mechanisms in the proximal tubule of the kidney and blood pressure control. With grant support from NIH/NIDDK and NIH/NIGMS, respectively, we are currently studying: 1) the molecular and signaling mechanisms by which extracellular (circulating and intrarenally formed) ANG II is taken up by the proximal tubule of the kidney to act as an intracellular peptide, 2) high resolution confocal and/or electron microscopic localization of the internalized ANG II and its receptors in intracellular organelles and nucleus,  3) the effects and signaling mechanisms by which intracellular ANG II induces long-term genomic effects, 4) the role of the sodium and hydrogen exchanger 3 (NHE3) selectively in the proximal tubule on pressure natriuretic and blood pressure responses to extracellular and intracellular ANG II; and 5) the role and signaling mechanisms of ANG II/AT1a receptors in the regulation of urine concentration in the renal medulla. To test our hypotheses, we use complementary state of the art approaches including: 1) live cell multicolor fluorescent imaging, 2) high resolution electron microscopic autoradiography and immunohistochemistry, 3) intravital multi-photon functional imaging, 4) proximal tubule cells derived from human kidney, wild-type, AT1a (AT1a-KO) and AT2 (AT2-KO) receptor-deficient mice, 5) proximal tubule-specific knockout of AT1a receptors (PT-AT1a-KO) or NHE3 (PT-NHE3-KO), 6) proximal tubule-specific knockin or overexpression of an intracellular cyan fluorescent fusion of ANG II protein (ECFP/ANG II) or a fusion ANG II protein (fsANG II), which is secreted upon expression, and 7) gene microarrays, phosphoproteomic and western blot analyses.

    Selected recent publications

    • Zhuo, J.L. (2014) AT2 receptors in cortical collecting ducts: a novel role in mediating ROMK-like K+ Channels' response to high K+ diet. American journal of physiology renal physiology 307(10):F1134-F1135. PubMed article
    • Li, X.C., Gu, V., Miguel-Qin, E., and Zhuo, J.L. (2014) A novel role of caveolin 1 in AT1a receptor-mediated uptake of angiotensin II by proximal tubule cells.  American journal of physiology renal physiology 307(8):F949-F961. PubMed article
    • Li, X.C. and Zhuo, J.L. (2014) Mechanisms of AT1a receptor-mediated uptake of angiotensin II by proximal tubule cells: a novel role of the multi-ligand endocytic receptor megalin. American journal of physiology renal physiology 307(2):F222-F233. PubMed article
    • Li, X.C. and Zhuo, J.L. (2013) Proximal tubule-dominant transfer of AT1a receptors induces blood pressure responses to intracellular angiotensin II in AT1a receptor-deficient mice. American journal of physiology, Regulatory, integrative and comparative physiology 304(8), R588-R598. PubMed article
    • Li, X.C. and Zhuo, J.L. (2013) Current insights and new perspectives on the roles of hyperglucagonemia in non-insulin-dependent type 2 diabetes. Current hypertension report 15(5), 522-530. PubMed article
    • Zhuo, J.L., Ferrao, F.M., Zheng, Y. and Li, X.C. (2013) New frontiers in the intrarenal renin-angiotensin system: a critical review of classical and new paradigms. Frontiers in endocrinology (Lausanne). 4:166. PubMed article
    • Zhuo, J.L.,and Li, X.C. (2013) Proximal nephron. Comprehensive physiology 3(3), 1079-1123. PubMed article
    • Li, X.C., U. Hopfer., and Zhuo, J.L. (2012) Novel signaling mechanisms of intracellular angiotensin II-induced NHE3 expression and activation in mouse proximal tubule cells. American journal of physiology. Renal physiology 303(12), F1617-F1628. PubMed article  
    • Li, X. C., Shao, Y., and Zhuo, J. L. (2012) AT1a receptor signaling is required for basal and water deprivation-induced urine concentration in AT1a receptor-deficient mice, American journal of physiology. Renal physiology. 303:F746-F756. PubMed article
    • Ellis, B., Li, X. C., Miguel-Qin, E., Gu, V., and Zhuo, J. L. (2012) Evidence for a functional intracellular angiotensin system in the proximal tubule of the kidney, American journal of physiology. Regulatory, integrative and comparative physiology 302, R494-509. PubMed article