Faculty

Jia L. Zhuo, MD, PhD

Professor
Office: G323
(601) 984-1707
Fax: (601) 984-1637

Research interests

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

Current research

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 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