Tuberculosis (TB) persists as a threat to human health globally. The causative agent, Mycobacterium tuberculosis, currently infects an estimated 2 billion people, and kills 1-2 million people annually. The only available vaccine has poor efficacy and TB treatment remains difficult, requiring protracted courses of multiple potentially toxic antibiotics.
Our laboratory’s long-term goal is to define the determinants of an effective innate immune response to M. tuberculosis infection, as well as to elucidate the mechanisms by which Mtb disrupts these responses to establish a replicative niche. We take an integrated approach, using a variety of proteomic methods to discover novel host pathways responding to M. tuberculosis infection. We then use molecular genetics in both the host and the bacterium to identify the pathways that contribute to effective host immunity and to bacterial virulence, in order to gain the mechanistic understanding needed to rationally explore future therapeutic strategies.