We study bacterial pathogenesis. The primary interest is in interactions between pathogenic Escherichia coli and host cells. We use a combined molecular biology, cell biology, and biochemistry approach to gain insight into the processes by which pathogenic E. coli cause disease. The goal is to identify and characterize bacterial factors that are involved in interactions with host cells and to identify cellular mechanisms triggered by interactions with bacteria. Our initial approach, to identify, clone and mutate bacterial genes involved in pathogenesis has led to the characterization of large gene clusters and pathogenicity islands required for adherence, host cell damage, and avoidance of host immune responses. We are currently involved in delineating the functions and cellular targets of the protein products of these genes. One of our current projects seeks an understanding of a molecular machine required for assembly of a bacterial surface appendage. Another aims to define the pathways disrupted by a protein injected into host cells that induces apoptosis and tight junction disruption. It is anticipated that these studies will impact not only our understanding and approach to infectious diseases, but also our appreciation for normal and abnormal cellular physiology. Further information is available on our laboratory website (http://som1.umaryland.edu/infeMSD /som.html).