Phone: (914) 594-4139/4120/4737
Department of Pharmacology
Basic Science Building, Rm. 527A
15 Dana Road
Valhalla, NY 10595
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:
Molecular, biochemical and electrophysiological approaches are being used to study the molecular mechanisms involved in the regulation of renal K+ channels. We have found that protein tyrosine kinases and WNK+ (with-no-lysine kinase) play an important role in the regulation of renal K+ secretion. Using miRNA+ array we have also identified several miRNA+ that regulate renal K+ channels - these include miR-802, miR-192 and miR142-3P.
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: