Part of the lab focuses on how P. aeruginosa , an opportunistic pathogen of man, injures epithelial cells. The common element underlying these opportunistic infections is the ability of P. aeruginosa to colonize and further damage injured epithelium surfaces, leading to local tissue damage and dissemination to distant organs. Initially we carried out a novel genetic screen to identify mutants that are deficient in injuring epithelial cells in vitro. This analysis has revealed that pili and products of a novel secretion system (type III secretion), are required for host cell injury by P. aeruginosa and identified a new cytotoxin, ExoU. C urrently, our work focuses on several aspects of P. aeruginosa -host cell interactions. First, we are further characterizing the pathway by which P. aeruginosa enters the apical and basolateral surfaces of into polarized and non-polarized epithelial cells. We are applying a genome-wide RNAi-based screen to identify host genes required for binding and uptake. Second, we are dissecting the function of the type III secreted effector ExoT and have found several unexpected functions for the ADP ribosylase. Third, we are continuing our studies of the functions and roles of the novel protein FimL and the products of the Chp regulon, likely involved in a complex signal transduction pathway that responds to environmental signals, in pilin biogenesis. Together, these studies will expand our knowledge of bacterial pathogenesis, host cell injury, and pilin function and may identify new targets for drug and vaccine development.

C. trachomatis is the leading cause of venereal disease and preventable sterility in the United States and the most common cause of non-congenital blindness in third world countries. It replicates via a unique developmental cycle involving the serial alternation of two distinct forms sequestered within a membrane bound compartment (the "vacuole") in the cytoplasm of the infected epithelial cell. While this organism presents major experimental challenges, its importance as a human pathogen merits overcoming the difficulty in manipulating and growing the bacteria in the laboratory. Our recent studies have been aimed at studying the interactions between C. trachomatis and the host epithelial cell. We have applied genome-wide RNAi-based screens to identify host factors required for early steps in the infection process.