Research Interest

Our laboratory studies protein trafficking in the secretory and endocytic pathways. These pathways are critically important in cell biology since a number of diseases including familial hypercholesterolemia and cystic fibrosis result from protein sorting defects within these pathways. Our model protein is the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that is defective in cystic fibrosis (CF). This channel is present at the apical surface of a number of epithelial cell types and is responsible for anion transport. Cystic fibrosis is caused by the failure of epithelial cells to produce or deliver physiologically active CFTR channels to the apical surface of airway, intestinal, and pancreatic epithelia. The most common mutation in CF, ΔF508 (deletion of phenylalanine at the 508 position), results in a protein that is misfolded and degraded at the endoplasmic reticulum (ER) during biogenesis. Physiological studies have shown however, that the ΔF508 mutant channel partially retains its function when delivered to the cell surface. Therefore, we are testing different methods for releasing the ΔF508 CFTR protein from the ER as a possible therapeutic approach. Once ΔF508 CFTR reaches the surface, it appears to be more rapidly internalized and degraded than the wild type protein. Our main focus is to determine the molecular mechanisms that regulate the surface pool of CFTR and to establish how mutations in CFTR disrupt surface stability and biological function. Our hypothesis is that by understanding these cellular processes in detail, we will be able to develop biochemical methods for enhancing chloride channel function at the apical surface for a number of CFTR mutations. We utilize biochemical, morphological and physiological methods to accomplish these goals.

Potential Rotation Project:

1. Determine the degradative pathway for cell surface CFTR

2. Analyze CFTR binding proteins in epithelial cells

Current Lab Members:

Rebecca Fazio (graduate student)

Asta Jurkuvenaite (graduate student)

Karoly Varga (research associate)

Biography

Dr. James F. Collawn, Professor of Cell Biology, received his B.S. from the University of South Carolina and his Ph.D. in Biochemistry from the Medical University of South Carolina (1986). He completed his postdoctoral training in immunology at The Scripps Research Institute and in molecular and cellular biology at The Salk Institute in La Jolla, California. After working for two years as a Staff Scientist at The Salk Insitute, Dr. Collawn joined the Department of Cell Biology in 1993.