Few infectious diseases in history have had the intimate, long-term association with humans and the profound global impact of tuberculosis (TB). Today, there are nearly 16 million active cases of TB causing 1.4 million deaths annually, and the World Health Organization estimates that roughly 25% of the world population (1.8 billion people) carries tuberculosis. TB causes untold morbidity and mortality, and the work in the Sherman Lab is focused on developing novel drugs, diagnostics and vaccines to combat this devastating disease.
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.
New Drugs for TB
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.
Hernandez and Sherman Labs awarded NIH grant to combat Mycobacterium abscessus
April 2019 – The Hernandez and Sherman Labs have been awarded a $250,000 NIH grant from NIAID with collaborators at the University of Michigan. The two-year grant funds a cross-institution collaborative pilot project that will measure the effectiveness of a panel of drug combinations targeting Mycobacterium abscessus (MABSC), a bacterium related to tuberculosis that causes difficult to treat infections in patients already suffering from other lung diseases. Cure rates for MABSC infections can be 20% or less; and recent evidence suggests that highly drug resistant strains may spread through susceptible populations, such as patients with cystic fibrosis.
The Sherman Lab previously worked with collaborators at the University of Michigan to build a model (INDIGO) for identifying drug combinations active against tuberculosis. The Hernandez and Sherman Lab will adapt the INDIGO model to predict how well novel antibiotic combinations will work against MABSC and then test the effectiveness of these combination therapies in a preclinical model to identify antibiotic regimens that may soon prove useful in the clinic.
CGIDR Researchers Awarded $17.2 Million Tuberculosis Grant from NIH
The Researchers from the Center for Global Infectious Disease Research (CGIDR) have been awarded a grant from the National Institute of Allergy and Infectious Diseases, one of the U.S. National Institutes of Health, to take a systems-level approach to the critical problem of tuberculosis (TB) infection, specifically focusing on the progression from infection to disease, and variability of treatment. The research ultimately seeks to catalyze new, transformative interventions, such as diagnostics, drugs and vaccines. Read more.
About Dr. David Sherman
David Sherman, PhD is a member of the Center for Global Infectious Disease Research at Seattle Children’s Research Institute and Professor and Department Chair in the Department of Microbiology at the University of Washington. His research focuses on virulence, latency and drug discovery for M. tuberculosis. He earned his BA from the University of California, Berkeley, and his PhD in biochemistry from Vanderbilt University, and he performed post-graduate work at the Rockefeller University and at Washington University in St. Louis. He joined the center in 2007 and has helped lead the TB research efforts ever since. On a personal level, Sherman loves hiking, skate skiing and cooking. He often completes 60-minute gourmet recipes in less than 40 minutes. Children and dogs love him. He is far too modest to take pleasure from the fact that you are reading about him right now.