Professor in the Department of Immunology and Infectious Diseases
65 Landsdowne Street
Cambridge, MA 02139
Our lab focuses on the molecular nature of interactions between microbial pathogens and the host, using the intracellular bacterial pathogen Shigella. Shigella utilizes a highly sophisticated mechanism (“injectosomes” or type III secretion) to induce its uptake into the cytoplasm of host intestinal epithelial cells. Once in the cytoplasm, it actively recruits host cytoskeletal proteins to form an “actin tail” at one end of the bacterium, a process that generates force sufficient to propel it through the cytoplasm and that leads to spread into adjacent cells. Through these mechanisms, Shigella causes dysentery and diarrhea. A major focus of the research in our laboratory is the molecular mechanisms by which bacterial proteins trigger host pathways to mediate these processes. Our approaches include both genome-wide screening and targeted investigations.
A remarkable characteristic of the Shigella actin assembly protein (IcsA) is its localization to the old pole of the bacterium. Precise spatial positioning of proteins is key to many cellular functions in prokaryotes; however, as yet, the basic mechanisms that mediate this positioning remain largely unknown. We have shown that the mechanism by which IcsA is positioned in the cell is representative of a general mechanism of protein positioning that is fundamental to bacterial cell biology and is present in a wide range of bacterial organisms. A second major focus of our research is to characterize the molecular mechanisms of spatial positioning of proteins in bacteria.