Dr. Sorscher has two major research interests. He directs the UAB Cystic Fibrosis Research Center that performs respected studies concerning molecular pathogenesis of this disease. His own laboratory investigates the structure and function of the gene product responsible for cystic fibrosis (i.e., the cystic fibrosis transmembrane conductance regulator, CFTR), and also evaluates new approaches to therapy, including the activation of alternate chloride secretory pathways in cystic fibrosis epithelia, molecular correction of mutant CFTR, and gene transfer-related aspects of cystic fibrosis using both viral and non-viral vectors. The other major interest in Dr. Sorscher’s laboratory involves the characterization of a novel mechanism for tumor sensitization using the E. coli PNP gene. In this approach, tumors are rendered hundreds or thousands of times more sensitive to conventional chemotherapy by expression of a prokaryotic enzyme that cleaves nontoxic nucleoside prodrugs to a very toxic form. The research involves analysis of the crystal structure of E. coli PNP, and structure-based drug design of novel compounds that would be effectively cleaved in vitro and in vivo. Gene transfer vectors that might be important in the treatment of human cancers are also developed and characterized.