Gene Regulatory Networks:
Throughout the infection cycle, there is an intricate dance between humans and the tuberculosis bacterium. The bacteria can manipulate host responses, while those same host responses feed back and alter the environment in which TB resides. Understanding how TB senses and responds appropriately in this shifting landscape is critical to our ability to design interventions that disrupt the chain. There are nearly 200 control proteins that coordinate the timing and magnitude of all of the genes in tuberculosis; however, in part due to the incredible complexity of the system, how these control proteins operate and interact has been a major challenge in the field of tuberculosis research. Using and developing cutting-edge systems biology approaches work in the Sherman Lab has illuminated unprecedented information in how tuberculosis senses its environment and parlays that information into an appropriate response. This work has resulted in several high-impact publications , as well as generated novel hypotheses for more effective types and combinations of antibiotics.
Other projects in the Sherman lab are focused on the identification of novel drug targets, and antibiotics. In highly interdisciplinary studies involving microbiologists, structural biologists, and chemists, the lab has studied the effect of treating tuberculosis with never-before used drug candidates. In a complementary interdisciplinary approach, we have discovered the impact of inhibition of critical pathways in TB and continue to develop novel antibiotic compounds to capitalize on these pressure points of the bacteria and push new drugs to the clinic.