My motivation for membership in the WGND is based on my primary research interest, which is the molecular basis of Mycobacterium tuberculosis latency and reactivation. My work focuses on developing new strategies for targeting persistent bacilli in order to shorten the duration of TB chemotherapy. Major research activities include studying the adaptation of M. tuberculosis to stress conditions believed to be important in the infected human host, as well as the phenomenon of phenotypic tolerance to antibiotics. In particular, the regulatory cascade involved in the mycobacterial stringent response is under active investigation. In collaboration with Dr. Joel Bader of the JHU Whiting School of Engineering, we have undertaken a systems biology-based approach, including the use of several novel animal models of latency in combination with transcriptional, proteomic, genetic, imaging, and computational techniques, to identify host cytokine networks responsible for immunological control of M. tuberculosis growth, as well as M. tuberculosis regulatory and metabolic pathways required for bacillary growth restriction and reactivation. We have also used the guinea pig model of TB, which forms necrotic lesions histologically resembling their human counterparts, to study the sterilizing activity of novel drugs and drug combinations against persisters.