EHSRC Role(s): Co-Director, Inflammation and Innate Immunity
Defense of all multi-cellular organisms from invading microbes depends on evolutionarily conserved systems that recognize and respond to highly conserved and unique microbial structures. The innate immune systems of the host include a broad array of proteins that together couple microbial recognition to activation of inflammation, killing and elimination of microbes and their remnants, and return of the host to a normal resting state. Our work concerns: 1) the molecular basis of microbial recognition by specific human innate defense proteins; 2) how this recognition is linked to specific cellular outcomes (e.g. activation (or de-activation) of host cells, elimination of viable microbes and their remnants); and 3) how the mobilization and function of these host proteins are regulated to permit an appropriate evolution of host responses to infection. In addition, we make use of the experimental setting of bacterial attack by defined host defense proteins to study the molecular bases of bacterial stress responses to sub-lethal injury and, in particular, repair of membrane damage. We hope these studies will provide new insights on the maintenance and regulation of (bacterial) membrane homeostasis and identify new targets for antibiotic development.