Clare Smith, Ph.D.

Research

The Smith lab is exploring how microbial and host factors contribute to the severity of tuberculosis. Infection with Mycobacterium tuberculosis can lead to a range of clinical outcomes, from cases that are mild and short-lived to those that are persistent, severe, and even fatal. Part of this variability lies in the host genetics and immune response, and part is due to the genetically diverse strains of M. tuberculosis in circulation. To begin to unravel this complex combination of factors, during my postdoctoral fellowship I infected nearly 100 genetically and immunologically diverse mouse strains with a pool of 100,000 knockout strains of M. tuberculosis. Now, using cutting-edge tools in bacterial and mammalian genetics, immunology, and molecular biology, I will identify specific genes—in the mouse and in M. tuberculosis—that drive disease susceptibility and influence the outcome of infection. In addition to recapitulating a broad spectrum of disease severity, we have identified diverse strains of mice that recapitulate the distinct disease states observed in human disease. My findings can be leveraged for the design of novel, more effective interventions and therapeutics.