Our laboratory studies the interplay between bacterial pathogens and their host cells. Specifically, we are examining how the obligate intracellular pathogen Salmonella manipulates host cell cytoskeletal and membrane trafficking machinery to drive its uptake into non-phagocytic epithelial cells, and its survival inside both epithelia and macrophages. We use a combination of genetic, biochemical and morphological approaches (confocal, live cell microscopy, EM) in vitro, and mouse models to define the roles of specific host molecules in pathogenesis in vivo.
We are also characterizing a novel pattern recognition receptor, BAI1, which mediates the clearance of Gram-negative bacteria by macrophages. We had previously shown that BAI1 recognizes the surface lipopolysaccharide (LPS) expressed by all Gram-negative species, and actively drives bacterial phagocytosis in macrophages. More recently we found that BAI1 not only mediates bacterial internalization, but is also required for the production of reactive oxygen species that ultimately kill internalized bacteria. We are currently working to define the signaling pathways that operate downstream of BAI1 and to define its role in bacterial clearance in vivo.