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Biography
BIOGRAPHICAL SKETCH
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NAME: Wang, Wen-Hui
eRA COMMONS USER NAME (credential, e.g., agency login): wenhui_wang@nymc.edu
POSITION TITLE: Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION DEGREE
(if applicable) END DATE
MM/YYYY FIELD OF STUDY
Harbin Medical University 07/1980 Medicine
University of Innsbruck, Austria MD 10/1983 Medicine/Physiology
A. Personal Statement
This project is to test the hypothesis that the basolateral Kir4.1/Kir5.1 is differently regulated by dietary potassium (K+) & sodium (Na+) and angiotensin II in early and late part of distal convoluted tubule (DCT1 and DCT2). I have the experience, expertise and motivation to be a qualified investigator for the proposed project. I have a broad background in the renal K+ and Na+ transport, with specific training and expertise in using electrophysiology to study the regulation of renal ion channels. My long-standing scientific interest is to understand the role of renal K+ channels in the regulation of kidney function and in the regulation of renal K+ excretion and Na+ absorption. My early publications have addressed the role of ROMK channels in mediating K+ secretion and the regulation mechanism of ROMK. I have now focused on studying Kir4.1 (encoded by Kcnj10) in the DCT. Kir4.1 plays a role in the regulation potassium homeostasis by controlling thiazide-sensitive NCC. Loss-of-function mutations of Kcnj10 cause EAST/SeSAME syndrome in humans (seizures, sensorineural deafness, ataxia, mental retardation and electrolyte imbalance). The renal phenotype of the disease is reminiscent to Gitelman’s syndrome including hypomagnesemia, hypokalemia and metabolic alkalosis, suggesting that the disruption of Kir4.1 mainly impairs transport in the DCT. We have demonstrated that Kir4.1 determines NCC function by regulating Cl--sensitive with-no-lysine kinase (WNK). Thus, Kir4.1 activity affects not only renal Na+ transport but also renal K+ excretion thereby affecting K+ homeostasis. My research has forwarded our understanding regarding management of hypokalemia or hyperkalemia, a potentially fatal disorder, occurs commonly in the setting of chronic kidney disease and heart failure. Thus, our research has a significant impact on basic science and clinical practice for handling renal potassium excretion.
Citations related to this application:
1. Cuevas CA, Su XT, Wang MX, Terker AS, Lin DH, McCormick JA, Yang CL, Ellison DH, Wang WH. Potassium Sensing by Renal Distal Tubules Requires Kir4.1. J Am Soc Nephrol. 2017; 28(6):1814-1825. PubMed PMID: 28052988; PubMed Central PMCID: PMC5461801.
2. Wu P, Gao ZX, Duan XP, Su XT, Wang MX, Lin DH, Gu R, Wang WH. AT2R (Angiotensin II Type 2 Receptor)-Mediated Regulation of NCC (Na-Cl Cotransporter) and Renal K+ Excretion Depends on the K+ Channel, Kir4.1. Hypertension. 2018; 71(4):622-630. PubMed PMID: 29483225; PubMed Central PMCID: PMC5843543.
3. Su XT, Klett NJ, Sharma A, Allen CN, Wang WH, Yang CL and Ellison DH. Distal convoluted tubule Cl concentration is modulated via K+ channels and transporters. American Journal of Physiology-Renal Physiology 319: F534-F540, 2020. PMID: 32715757 ,PMCID: PMC7509289 .
4. Duan XP, Wu P, Zhang DD, Gao ZX, Xiao Y, Ray EC, Wang WH, Lin DH. Deletion of Kir5.1 abolishes the effect of high Na+ intake on Kir4.1 and Na+-Cl- cotransporter. Am J Physiol Renal Physiol. 320(6):F1045-F1058, 2021.PMID: 33900854
Ongoing projects that I would like to highlight include:
RO1 DK 54983 Wang/Ellison (M/PI) 08/29/2016-05/31/2022 (NCE)
NIH/NIDDK
Role of Kir4.1 in regulating NCC and ROMK in DCT
To study the role of Kir4.1 in the DCT in mediating the effect of hyperkalemia and hypokalemia on NCC and ROMK activity
Role: PI
RO1 DK115366 PI: Dao-Hong Lin 12/25/2017-11/30/2021
NIH/NIDDK
Kir5.1 regulates Kir4.1 ubiquitination by Nedd4-2 in DCT
The aim of the project is to explore the role of Kir5.1 and Nedd4-2 in the regulation of Kir4.1 ubiquitination and in mediating the effect of dietary sodium intake on NCC in the DCT.
Role: Co-Investigator
B. Positions, Scientific Appointments, and Honors
Positions and Employment
1984-1985 Lecturer, Dept. of Physiology, Harbin Medical University, Harbin, China
1986-1987 Postdoctoral Fellow, Dept. of Physiology, University of Wuerzburg, Wuerzburg, Germany
1987-1988 Postdoctoral Fellow, Dept. of Cell. & Mol. Physiology, Yale University, New Haven, CT
1989-1992 Associate Research Scientist, Dept. of Cell. & Mol. Physiology, Yale University, CT
1993-1995 Assistant Professor, Dept. of Pharmacology, New York Medical College, Valhalla, NY
1996-2000 Ass
Activities
Employment (1)
Funding (1)
DK133220