The wide range of disease outcomes remains a mystery of H. pylori pathogenesis. Our lab is interested in the mechanisms by which this bacterium can establish and maintain a chronic infection in the unusual environment of the human stomach and the molecular cross talk between the host and the bacteria during the decades long infection. Our current projects include:1) H. pylori genomic diversity: We are currently investigating how this diversity is generated and the consequences of this diversity on patient outcome. 2) Genetic Analysis of H. pylori virulence factors: We use gastric epithelial tissue culture cells to monitor wild-type and mutant bacteria binding to host cells and stimulation of host cell signaling pathways including those activating innate immunity and cell shape changes. Most recently we have been exploring the genetic requirements for establishing the spiral shape of this bacterium using fluorescence activated cell sorting technologies.3) Mechanistic studies of H. pylori virulence: we have begun to explore the mechanistic details of how H. pylori genes contribute to persistent colonization.3a) Cell wall modification and cell shape: We currently are testing motility in viscous solutions, susceptibility to various stresses and peptidoglycan-mediated innate immune signaling to tease out how these proteins and shape itself contribute to survival in the host.3b) DNA metabolism: A surprising outcome of our colonization screen was that genes involved in DNA metabolism contribute to stomach colonization. We currently are testing several models including genetic interactions between DNA competence and recombination-based DNA repair.