NYMC > Faculty > Directory > By Name > Wang, Wenhui

Wenhui Wang, M.D.

Professor of Pharmacology

E-mail:  wenhui_wang@nymc.edu

Tel:        914-594-4139/4120/4737

Mail:

Department of Pharmacology
Basic Science Building, Rm. 527A
15 Dana Road
Valhalla, NY  10595

Research Interests

My laboratory is focused on studying the regulation of Na+ and K+ transport in aldosterone-sensitive distal tubules of the kidney. Na+ is a major extracellular ion and plays a key role in maintaining extracellular volume, and decreasing extracellular Na+ content can result in hypotension whereas increasing Na+ content causes hypertension. Conversely, K+ is mainly located in the intracellular fluid and extracellular K+ must be maintained in a narrow range: either high plasma K+ (hyperkalemia) or low plasma K+ (hypokalemia) can cause life-threatening cardiac arrhythmias. The kidney plays a key role in secreting K+ to match the dietary K+ intake, and disorders of K+ balance are common in patients with kidney failure.

We have two research projects funded by the National Institutes of Health.

Regulation and Modulation of Renal K+ channels in Kidney:

My recent work is focusing on the role of inwardly-rectifying K channel 4.1 (Kir4.1) in the regulation of Na and K transport in the distal convoluted tubule (DCT). Loss-of-function mutations of Kir4.1 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 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 in the DCT serves as a potassium sensor and plays a key role in regulating NCC activity and Na/K transport through WNK-SPAK pathways in the aldosterone-sensitive distal nephron (ASDN). Thus, understanding the regulation of Kir4.1 should have a significant impact on Na and K homeostasis.

Regulation of Epithelial Na+ Channels by epoxyeicosatrienoic acids (EETs):

Arachidonic acid can be metabolized to EETs by the cytochrome P450 epoxygenase CYP2C44, and we have found that EETs play an important role in the regulation of Na+ transport in the distal nephron. High Na+ intake stimulates CYP2C44 activity and thus inhibits Na+ absorption in the distal nephron, and defective regulation of CYP2C44 can cause the salt-sensitive hypertension. We are currently using genetically modified mice to study the role of CYP2C44 in regulating epithelial Na+ channels in the kidney.

Selected Publications in the last 5 years:

  1. Zhang C, Wang L, Thomas S, Wang K, Lin DH, Rinehart J, Wang WH. Src family protein tyrosine kinase regulates the basolateral K channel in the distal convoluted tubule (DCT) by phosphorylation of KCNJ10 protein. J Biol Chem. 2013 Sep 6;288(36):26135-46. doi: 10.1074/jbc.M113.478453. Epub 2013 Jul 19. PubMed PMID: 23873931; PubMed Central PMCID: PMC3764816.
  2. Zhang C, Wang L, Zhang J, Su XT, Lin DH, Scholl UI, Giebisch G, Lifton RP, Wang WH. KCNJ10 determines the expression of the apical Na-Cl cotransporter (NCC) in the early distal convoluted tubule (DCT1). Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11864-9. doi: 10.1073/pnas.1411705111. Epub 2014 Jul 28. PubMed PMID:  25071208; PubMed Central PMCID: PMC4136599.
  3. Wang L, Zhang C, Su X, Lin DH, Wang W. Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport. J Am Soc Nephrol. 2015 Apr 6. pii: ASN.2014070658. [Epub ahead of print] PubMed PMID: 25848073.
  4. Terker AS, Zhang C, McCormick JA, Lazelle RA, Zhang C, Meermeier NP, Siler DA, Park HJ, Fu Y, Cohen DM, Weinstein AM, Wang WH, Yang CL, Ellison DH. Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride. Cell Metab. 2015 Jan 6;21(1):39-50. doi: 10.1016/j.cmet.2014.12.006. PubMed PMID: 25565204; PubMed Central PMCID: PMC4332769.
  5. Su XT, Zhang C, Wang L, Gu R, Lin DH, Wang WH. Disruption of KCNJ10 (Kir4.1) stimulates the expression of ENaC in the collecting duct. Am J Physiol Renal Physiol. 2016 May 1;310(10):F985-93. PMID: 26887833
  6. 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
  7. Wang MX, Cuevas CA, Su XT, Wu P, Gao ZX, Lin DH, McCormick JA, Yang CL, Wang WH, Ellison DH. Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel. Kidney Int. 2018 Jan 6. pii: S0085-2538(17)30803-7. doi: 10.1016/j.kint.2017.10.023. [Epub ahead of print] PubMed PMID: 29310825.

PubMed Publications – Wenhui Wang, M.D.