Mycobacterium as Pathogen, Model System, and Cancer Therapy
We are broadly interested in the biology of mycobacteria, which include the major human pathogen M. tuberculosis, the nonpathogenic model organism M. smegmatis, and the cancer biotherapeutic agent BCG.
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, as well as CD4 T cell responses to Mtb.
We also believe that mycobacteria are a fertile system to study prokaryotic biology, particularly DNA repair. 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.
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.