Molecular mechanism of anion permeation through CFTR channel pore.

Abstract

The proposed research in my lab has been focusing on the structure, function and molecular pharmacology of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel; and the interaction of CFTR chloride channels with other ion channels, receptors in submucosal gland cells. Chronic lung infection and deterioration of lung function are the major causes of morbidity and death in cystic fibrosis (CF), the most common inherited lethal disease in Caucasians. Although the genetic defect in CF was discovered in 1989-mutations in the gene encoding the CFTR, the mechanism by which CFTR mutations cause lung disease remain uncertain. We arc very interested in studying a number of mechanisms proposed to link the CF genotype to clinical disease, particularly in defective airway submucosal gland secretion, loss of CFTR regulation of other transporting proteins such as other chloride channels, potassium channels, aquaporins in a serous epithelial cells. Determination of the mechanism linking genotype to disease is of crilical importance in developing therapies to treat CF.