Raman Deep Singh

Biography

The doctoral work carried out at Department of Biochemistry, University of Delhi South Campus focused on analysis and characterization of genes associated with M. tuberculosis pathogenesis. We were the first research group to experimentally prove that mycobacterial protein tyrosine phosphatases are indeed involved in pathogenesis of mycobacteria. I was also involved in studies evaluating the protective efficacy of recombinant BCG, DNA vaccines either alone or in a prime boost approach in guinea pigs model of tuberculosis, After obtaining my Ph.D., I moved to Tuberculosis Research Section at National Institutes of Health, MD. During my post-doctoral tenure, we collaborated extensively with the Novartis Institute for Tropical Diseases, Singapore to understand the mechanism of action of bicyclic nitroimidazole, a drug currently in phase2a clinical trials. We have shown that activation of PA-824 by Deazafllavin Dependent Nitroreductase (Ddn) resulted in formation of 3 major metabolites; the major one is corresponding des-nitro imidazole. Des-nitro metabolite formation resulted in generation of reactive nitrogen species, including nitric oxide, which are the major effectors of the anaerobic activity of these compounds. We have also built a QSAR model for activation of bicyclic nitroimidazoles by a Ddn, which should facilitate our collaborative on-going effort to synthesize a more potent bicyclic nitroimidazoles. Another aspect of research at NIH was to understand mechanism of persistence of M. tuberculosis. The doctoral work carried out at Department of Biochemistry, University of Delhi South Campus focused on analysis and characterization of genes associated with M. tuberculosis pathogenesis. We were the first research group to experimentally prove that mycobacterial protein tyrosine phosphatases are indeed involved in pathogenesis of mycobacteria. I was also involved in studies evaluating the protective efficacy of recombinant BCG, DNA vaccines either alone or in a prime boost approach in guinea pigs model of tuberculosis, After obtaining my Ph.D., I moved to Tuberculosis Research Section at National Institutes of Health, MD. During my post-doctoral tenure, we collaborated extensively with the Novartis Institute for Tropical Diseases, Singapore to understand the mechanism of action of bicyclic nitroimidazole, a drug currently in phase2a clinical trials. We have shown that activation of PA-824 by Deazafllavin Dependent Nitroreductase (Ddn) resulted in formation of 3 major metabolites; the major one is corresponding des-nitro imidazole. Des-nitro metabolite formation resulted in generation of reactive nitrogen species, including nitric oxide, which are the major effectors of the anaerobic activity of these compounds. We have also built a QSAR model for activation of bicyclic nitroimidazoles by a Ddn, which should facilitate our collaborative on-going effort to synthesize a more potent bicyclic nitroimidazoles. Another aspect of research at NIH was to understand mechanism of persistence of M. tuberculosis.

Research Interest

Raman Deep’s Research interest includes Host-pathogen interactions using Mycobacterium as a model, Mechanisms of Virulence and Persistence of M. Tuberculosis, Identifying novel drugs against mycobacteria in a collaborative effort with other groups/industry and there by identifying novel drug targets for chemotherapy, Design better vaccines against mycobacteria.