Marcia Goldberg

Research Description

Our lab focuses on the molecular nature of interactions between microbial pathogens and the host. Pathogenic bacteria have evolved complex mechanisms to subvert host cell signaling pathways to enhance disease processes. Our work focuses on uncovering the molecular signaling events that occur during bacterial infection of host cells. The bacterial pathogen Shigella, a major cause of illness and mortality among children worldwide, infects cells of the intestinal epithelium and uses cellular actin cytoskeletal and other pathways to disseminate through host tissue. We are investigating the molecular mechanisms by which secreted bacterial proteins modulate host proteins to divert the host signaling pathways involved in these processes. Our approaches include both genome-wide screening and targeted investigations.

We have discovered that bacterial proteins delivered into host cells by Shigellamodulate pathways involved in human cancers. We are defining how this occurs, with the long-term goal of applying insights gained in these investigations to the development of new cancer therapeutics.

Inside the host cell cytoplasm, Shigella polymerizes host cell actin into a propulsive tail at one end of the bacterial body. Assembly of this tail generates the force to propel the bacterium to the cell periphery. A remarkable characteristic of the Shigellaactin assembly protein (IcsA) is its localization to the old pole of the bacterium. Secretion of proteins and their precise spatial positioning is key to many cellular functions in prokaryotes; however, as yet, the basic mechanisms that mediate this positioning remain largely unknown. We are characterizing the molecular mechanisms of secretion and spatial positioning of proteins in bacteria. In addition, we are collaborating with Drs. Deb Hung and David Weiss to use state-of-the-art RNA technology and microfluidics in the development of novel rapid diagnostics for infectious diseases.