I am a microbiologist engaged in basic research mastering microbial genetics and biochemistry of microorganisms. My research focuses on translational research of bacterial pathogens aiming at anti microbial drug development. My first major contribution to the field of Tuberculosis (TB) research was the identification of the “Eukaryotic – like” protein kinases of Mycobacterium tuberculosis, a new family of proteins which play a role in the bacterial adaptive gene expression and cross-talk with the infected human macrophages. This discovery opened a new field of research into signaling elements of M. tuberculosis and gained my laboratory leading recognition in mycobacterial signal transduction research. In collaboration with industry my group has shown that small molecules targeted against one of these kinases can block the growth of M. tuberculosis within macrophages and thus can be used as novel anti-TB therapy. Using proteomics and global kinome analysis my team showed that mycobacterial infection triggers a signaling cascade leading to activation of stress-activated protein kinases. More recently, our research identified an M. tuberculosis Phosphatase, PtpA, which inhibits macrophage “normal” response to infection by targeting host signaling proteins and the macrophage acidification machinery. To show that we used gene knock-out and substrate trapping technologies and a novel technique, neutralizing PtpA in vivo by expressing intracellular single chain antibodies within the TB infected macrophage. My research into nitric oxide reveal its role in activating M. tuberculosis kinases and identified the thiol-based mechanism used by mycobacteria to protect themselves from nitric oxide damage. We have translated our basic research into commercialization by licensing his technologies to various companies.
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