Senior Fellows
Gobardhan Das
PhD Institute of Microbial Technology, Chandigarh
Post-PhD Yale University School of Medicine, New Haven
Aventis Pharmaceuticals, New Jersey
Robert wood Johnson Medical School, New Jersey
Senior Fellowship research summary
The only available tuberculosis (TB) vaccine, BCG, is not effective for adult pulmonary tuberculosis. Conventional drug therapy of TB is lengthy, expensive, and has a high risk of generating multiple drug-resistant (MDR) and extensively drug-resistant (XDR) strains of M.tb. We propose small molecule-directed immunotherapy, which avoids direct interaction of the drug with the tuberculoid organisms, which has three advantages over conventional antibiotic treatment: 1) expulsion of the harbored tuberculoid organisms, 2) generation of signature protective memory responses, and 3) lack of selection for drug-resistant forms of tuberculosis (MDR and XDR).
It is clear that T helper 1 (Th1) and Th17 cells are required for disease resistance, whereas Th2 and Treg cells assist the progression of tuberculosis. Thus, it is very likely that promoting Th1 and Th17 responses and simultaneously inhibiting Th2 and Treg responses holds the key to effective resistance against TB. Differentiation and activation of Th cells are directed by Antigen Presenting Cells (APCs) by providing MHC bound peptide, co-stimulatory molecules, and appropriate Th cell differentiating cytokines. M. tb infects and survives and replicates within phagocytes, which are the professional APCs. Therefore, we will identify and validate druggable targets from the M.tb infected phagocytes, inhibition of which will promote productions of IL-12, IL-6, & IL-23; and inhibits productions of IL-10, and TGF-b??? simultaneously. This microenvironment will create a niche for the differentiation of M.tb antigen specific Th1 and Th17 cells, whereas Th2 and Tregs will be suppressed.
Das Lab Website
( http://www.icgeb.org/g-das-lab.html )