Our studies with M. tuberculosis seek to understand the pathways used by this pathogen to cause disease and the host immune response to this persistent infection. We have focused on the biosynthesis of the M. tuberculosis cell envelope, the regulation of that synthesis, and signal transduction across the envelope via regulated intramembrane proteolysis, and metal acquistion and resistance.
We also believe that mycobacteria are a fertile system to study prokaryotic biology, particularly DNA repair and transcription. We are studying DNA repair in mycobacteria not only because the host inflicts DNA damage upon the bacterial chromosome during infection, but also because mycobacteria express a unique array of repair pathways (for example, nonhomologous end-joining) not previously described in prokaryotes. Chromosomal mutagenesis is also the origin of antibiotic resistance in TB, making the study of mutagenesis pathways relevant to combating AMR.
Finally, we study the interaction of BCG with bladder cancer cells. Although used worldwide as a vaccine for M. tuberculosis, BCG is also a highly effective biotherapy for bladder cancer. We are seeking to understand the mechanism of action of BCG in the treatment of bladder cancer, with the ultimate goal of improving its efficacy and predicting which patients will respond to BCG therapy. We recently demontrated that BCG acts as a systemic immunotherapy by modifying myeloid function of the tumor microenvironment.
Biography
Michael Glickman is a physician-scientist who studies mycobacteria. The Glickman lab is broadly interested in the biology of mycobacteria, including virulence determinants of the major human pathogen M. tuberculosis, physiology of mycobacteria studied in the nonpathogenic model organism M. smegmatis, and the mechanisms of the cancer immunotherapy agent BCG.
