The central theme of our research program is to understand the host response to microbial infections of humans, particularly bacterial and fungal diseases, using animal and in vitro models. We are well-recognized for research in tuberculosis, specifically for the rabbit model. In this area, one of the goals is to determine, characterize, understand and apply the molecular immunologic and metabolic determinants underlying the progression of Mycobacterium tuberculosis (Mtb) infection to active tuberculosis (TB) versus control of infection and establishment of latency (LTBI) as well as reactivation of TB upon immune suppression. Another aspect of our research involves exploring the efficacy of adjunctive immune modulation therapy as a host-directed intervention to improve current TB treatment modalities. For these studies, we have been primarily using rabbit, mouse, rat and guinea pig; each of these models recapitulates various pathophysiological aspects seen in patients with active and/or latent TB to various extents.For the first time in literature, we have identified/reported several host gene networks/pathways that contribute to the differential outcome of Mtb infection. We have established proof-of-concept for the beneneficial effect of host directed therapy with a small molecule phosphodiesterase-4 inhibitor (PDE4i) in combination with anti-TB drugs; at present, this molecule is in human clinical trial.
PHD, 2003, University of Madras, Chennai, India
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