Fundamental processes underlying infectious disease.
We are interested in interferon (IFN)-stimulated host defense mechanisms against intracellular bacterial pathogens such as Chlamydia trachomatis and Legionella pneumophila. To exert their antimicrobial activities, many IFN-induced host proteins must specifically localize to pathogen-containing vacuoles (PCV). The mechanisms by which the host recognizes and discriminates between ‘non-self’ PCV and endogenous ‘self’ membranous structures, such as mitochondria or the Golgi apparatus, are not well understood. One of the main interests of our lab is to elucidate the molecular mechanisms that direct the localization of antimicrobial proteins to PCV. Towards this goal we are taking two complementary approaches:
(I) We conduct mammalian RNAi screens to identify host genes required for PCV targeting
(II) We use bacterial genetics, cell biological and biochemical techniques to determine what PCV-associated properties are recognized by the innate immune response
A second interest of the lab is to understand how the obligate intracellular bacterial pathogen C. trachomatis can cause chronic genital infections, infertility and other complications in women. Currently, no small animal model exists that recapitulates the chronic disease as it manifests itself in humans. We and others have found that humans and mice differ substantially in their respective IFN-gamma response pathways and these differences emerge as key determinants of host tropism. Therefore, a goal of our lab is to develop and study mouse models that more accurately reflect the pathogenesis of human C. trachomatis infections. To achieve this goal we are engineering Knock-In mice in which the IFN-gamma response closely resembles that of humans. Ultimately, by furthering our understanding of host-pathogen interactions, our research will support the development of more effective, alternative therapeutic strategies to treat microbial infections.