Research & Publications
My laboratory has been supported continuously by NIH awards (K08, R03, R01) since 2000. We study intracellular trafficking routes and mechanisms and that regulate the expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in the intestine. CFTR represents the primary exit pathway responsible for anion and fluid secretion on the apical membranes of intestinal cells. Mutations in the CFTR gene result in absence of functional CFTR channels and the genetic disease Cystic Fibrosis while up-regulation of CFTR function is implicated in diarrheal diseases. We employ transgenic animal and polarized intestinal cell models in conjunction with cell biologic, molecular and physiologic approaches to understand the intracellular trafficking routes traversed by CFTR and how alterations in these pathways lead to intestinal diseases.
Extensive Research Description
Our early studies focussed on identification of trafficking as a major mechanism regulating CFTR in the intestine and its relevance to secretory diarrhea. More recently, we investigate a rare genetic diarrheal disease that affect new borns, Microvillus Inclusion Disease(MVID). We were first to show that MVID results from an apical trafficking defect. Current investigations are elucidating kinase signaling mechanisms regulating ion transport that result in diarrhea in MVID.
Antidiarrheals; Intestinal Diseases