Dr. Daohong Lin Awarded $2,050,000 NIH Grant
Grant Awarded to Daohong Lin, Ph.D., Supports Vital Kidney Regulating
The project of Daohong Lin, Ph.D., assistant professor of pharmacology, entitled "Regulation of Kir4.1/Kir5.1 and renal K excretion", is focused on exploring the role of the renal potassium channel in handling K homeostasis.
The kidney is important for salt handling and maintaining sodium, potassium and other electrolytes' homeostasis. High salt intake will increase vascular tone and lead to elevated blood pressure and hypertension. The kidney will “sense” the increased delivered sodium amount and “determine” sodium-chloride cotransporter (NCC) activity, a diuretic Thiazide target, by “potassium sensor” to increase natriuresis. Basolateral K+ channel (K sensor) in the distal convoluted tubule (DCT) is composed of Kir4.1 and Kir5.1, “K sensor”, and plays an important role in the regulation of K+ excretion in the aldosterone-sensitive distal nephron by determining the activity of thiazide-sensitive Na-Cl cotransporter (NCC). The mechanism by which the basolateral K+ channel controls the NCC activity is mediated by Cl--sensitive with-no-lysine kinase. Kir4.1 in the DCT has been suggested to be a “K sensor” for the effect of dietary K+ intake on NCC, since the deletion of Kir4.1 abolishes the effect of dietary K+ intake on NCC and impairs the body K+ homeostasis. Dr. Lin’s work has demonstrated that the deletion of Kir5.1 abolishes the inhibitory effect of high K+ intake on NCC and impairs the renal ability of K+ excretion during increased dietary K+ intake.
Dr. Lin joined Dr. Wenhui Wang’s lab as a research fellow in the Department of Pharmacology at New York Medical College (NYMC), in March 2000 as a second-year Ph.D. student at Harbin Medical University, China, focused on studying the mechanism by which low potassium intake or high potassium intake affected inwardly rectifying potassium channels (Kir1.1, ROMK) in the collecting tubule in the kidney. During her post-doctoral training in Dr. Wang’s lab in 2005, she studied the endocytosis of ROMK channel (Kir1.1), a key K channel for renal K secretion in the kidney. Dr. Lin has used molecular, protein chemistry and electrophysiology approaches to study the roles of protein kinases, ubiquitination and microRNA in mediating the effect of dietary K intake on ROMK channels and observed that low K intake stimulated the protein tyrosine kinase phosphorylating ROMK causing ROMK ubiquitination and internalization. She found miR-802 mediated caveolin-1 induced ROMK endocytosis and received a Scientific Development Grant from the American Heart Association in 2011. Focusing her research on the regulation of Kir5.1(Kcnj16) on Kir4.1 (Kcnj10) channels in the kidney, Dr. Lin has been awarded NIH R01 funding in 2017 and 2023.
Dr. Lin notes, “The physiological significance of our study is to illustrate that like Kir4.1, Kir5.1 is also an essential component of the “K+-sensor” mechanism in the DCT and that Kir5.1 is indispensable for the renal K+ excretion and K+ homeostasis.”
