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Department of Microbiology Dr. Ramakrishnan received her M.B.B.S. in Vadodara, India in 1983 and her Ph.D. in Immunology at Tufts University, Boston in 1990. Prior to joining theUniversity of Washington in 2001, she did a medical residency at the Tufts-New England Medical Center in Boston, an infectious diseases fellowship at the University of California San Francisco and a post doctoral fellowship at Stanford University. Her research is funded by the National Institutes of Health, the Burroughs Wellcome Foundation and the Akibene Foundation. We are interested in understanding the pathogenesis of tuberculosis. Tuberculous infection results in the formation of granulomas, complex immune structures that are composed of differentiated macrophages, lymphocytes and other immune cells. However, bacteria can persist within granulomas despite the development of antigen-specific immunity. We are trying to understand the mechanistic basis of mycobacterial persistence, the mechanisms of granuloma formation and its role in tuberculosis. We have developed the zebrafish as model to study immunity to tuberculosis. Zebrafish are naturally susceptible to tuberculosis caused by Mycobacterium marinum, a close genetic relative of M. tuberculosis, the agent of human tuberculosis. We exploit the optical transparency and genetic tractability of the zebrafish to monitor the infection process in real-time and modulate it using genetically defined host and bacterial mutants. Our research is focused on identifying determinants of host susceptibility and resistance to tuberculosis using a forward genetic screen. Our goal is to understand how bacterial and host immune determinants interface to result in persistent infection. Our research should shed light on tuberculosis pathogenesis as well as fundamental mechanisms of immune cell chemotaxis, adhesion and aggregation as well as immune regulation. Students currently training in the Ramakrishnan Lab: Hilary Clay, Muse Davis, Hannah Volkman Recent publications: J.M. Davis, H. Clay, J.L. Lewis, N. Ghori. P. Herbomel and L. Ramakrishnan. 2002. Real-time visualization of Mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos. Immunity 17:693-702. T. Pozos and L. Ramakrishnan. 2004. New models for the study of Mycobacterium-host interactions. Current Opinion in Immunology 16:499-505. C. L. Cosma, O. Humbert, and L. Ramakrishnan. 2004. Superinfecting mycobacteria home to established tuberculous granulomas. Nature Immunology, 5:828-835. H. E. Volkmann, H. Clay, D. Beery, J.C.W. Chang, D. R. Sherman, and L. Ramakrishnan. 2004. Tuberculous granuloma formation is enhanced by a Mycobacterium virulence determinant. PLoS Biology, 2:1946-1956. C. L. Cosma, K. Klein, R. Kim, D. Beery, and L. Ramakrishnan. 2006 Mycobacterium marinum Erp is a virulence determinant required for cell wall integrity and intracellular survival. Infect. Imm, 74:3125-3133. L.E. Swaim, L.E. Connolly, H.E. Volkman, O. Humbert, D. E. Born, and L. Ramakrishnan 2006 Mycobacterium marinum infection of adult zebrafish produces caseating granulomatous tuberculosis and is moderated by adaptive immunity. Infect. Imm, 74:6108-17.
Medline database search for this researcher Updated January 2007
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