Michael Caplan Professor of Cellular & Molecular Physiology » Physiology and Integrative Medical Biology » Molecular Cell Biology, Genetics and Development » A.B. Harvard University 1980; M.D., Ph.D. Yale University 1987 The cell surface membranes of epithelial cells and neurons are divided into distinct domains, characterized by unique protein compositions and functional properties. We are interested in the molecular signals and cellular machinery involved in generating this polarity. We have recently found that members of the tetraspan family of membrane proteins interact with a wide variety of ion transport systems. Through direct associations, members of this family appear to play very significant roles in determining the subcellular distributions and dynamic properties of a number of different transport systems. Cystic fibrosis is a genetic disease that is attributable to the mis-trafficking of a membrane protein. Most cases result from mutations in the CFTR chloride channel that cause this protein to be retained in the endoplasmic reticulum. We are developing a new small molecule approach to liberating mutant CFTR protein from the ER such that it can achieve at least partial function at the cell surface. We have identified a compound that is non-toxic and appears to be effective in mouse models of cystic fibrosis. Our studies suggest that this compound exerts its effects by altering the interaction of CFTR with the chaperone proteins that retain it within the cell. Dunbar, L.A., Aronson, P.L., and Caplan, M.J. (2000). A transmembrane segment determines the steady-state localization of an ion transporting adenosine triphosphatase. J. Cell Biol. 148:769-778. Egan, M.E., et al. (2002). Calcium-pump inhibitors induce functional surface expression of dF508-CFTR protein in cystic fibrosis epithelial cells. Nature Medicine 8:485-492.