Our laboratory uses molecular biological methods to study the genetics and regulation of bacterial protein toxins, their roles in the pathogenesis of infectious diseases, and their uses for vaccine development.
Diphtheria toxin causes the serious manifestations of diphtheria.
DtxR, an iron-activated global regulatory protein of C. diphtheriae, negatively controls synthesis of diphtheria toxin. Cholera toxin and the closely related E. coli heat-labile enterotoxins cause the secretory diarrhea of cholera and traveler's' diarrhea, respectively. These toxins consist of a pentameric B subunit that binds to ganglioside receptors on target cells and an A polypeptide that activates adenylate cyclase by ADP ribosylation of the regulatory protein Gsa. Studies in our laboratory have focused on using genetic and biochemical methods to analyze the structure and function of these enterotoxins in vitro and the mechanisms for their uptake and trafficking in target cells. CT is also a potent mucosal antigen and immunomodulatory agent.