We are interested in molecular strategies utilized by intracellular pathogens to interact with their host cells, and on fundamental cell biological processes thatare subverted by pathogens during infection. Our studies of the mechanism by which the protozoan Trypanosoma cruzi invades host cells have uncovered a previously unrecognized, ubiquitous process of Ca2+ dependent mobilization and fusion of lysosomes with the plasma membrane. This Ca2+-regulated lysosome exocytosis pathway is subverted by the parasites as a strategy to form a membrane-bounded vacuole, through which they gain access to host cells. Current projects include the study of signaling pathways involved in lysosome mobilization and trypanosome entry, molecular mechanisms of intracellular survival of thetrypanosomatid Leishmania, and the role of a novel family of agonist-processing serine oligopeptidases we identified in trypanosomatids and bacterial pathogens. In addition, we are actively investigating the molecular mechanisms regulating Ca2+-triggered exocytosis of lysosomes in mammalian cells, and the role of this processin the repair of wounded membranes.
