The central focus of the Ameen laboratory is to understand how trafficking of proteins in the intestine lead to diarrheal diseases. Our studies over the years have focussed on elucidation of mechanisms by which apical trafficking (endocytosis, recycling and exocytic insertion) of the major chloride channel in the intestine, the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channels regulate fluid secretion and leads to diarrhea.
These studies are critical for identification of physiological targets for treating secretory diarrhea because currently no pharmacologic therapies are available to prevent the mortality resulting from severe diarrhea and intestinal fluid loss following infection with agents such as Cholera.
Our studies in native tissues were the first to demonstrate that under pathologic conditions such as enterotoxin exposure following Cholera or E.Coli, cAMP and cGMP second messenger signaling stimulate exocytosis of CFTR from endosomal vesicles to the apical membrane to increase CFTR surface expression and fluid secretion. We employ polarized intestinal cells and animal models to examine factors that regulate apical endocytosis, recycling and exocytic insertion of CFTR into the apical membrane in the intestine.