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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 the University 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, and she is the recipient of the NIH Director's pioneer award. We are interested in understanding the pathogenesis of tuberculosis and the basis of vastly different susceptibilities to this disease. 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. 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. We have employed both forward and reverse genetics to understand the basis of host resistance and susceptibility to TB. Our research is shedding light on TB pathogenesis as well as fundamental mechanisms of immune cell chemotaxis, adhesion and aggregation as well as immune regulation. Findings made in the zebrafish have been borne out in human populations and are informing new strategies for intervention. Students currently training in the Ramakrishnan Lab: Kristin Adams, Russell Berg, Sachi Seilie, and CJ Cambier. Recent publications: Tobin, D.M., Vary Jr, J.P. Ray, G.S. Walsh, S.J. Dunstan, N.D. Bang, D.A. Hagge, S. Khadge, M-C. King, T.R. Hawn, C.B. Moens, L. Ramakrishnan. The lta4h Locus Modulates Susceptibility to Mycobacterial Infection in Zebrafish and Humans. Cell 140:717-730. H. E. Volkman, T. C. Pozos, J. Zheng, J.M. Davis, F. Chu, J. F. Rawls, L. Ramakrishnan (2010). Tuberculous granuloma induction via interactions of a bacterial secreted protein with host epithelium. Science, 327:466-469. J.M. Davis and L. Ramakrishnan. 2009. The role of the granuloma in the expansion and dissemination of early tuberculous infection. Cell 136:37-49. H. Clay, HE Volkman and L. Ramakrishnan. 2008. TNF signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death but is not required for tuberculous granuloma formation. Immunity 29:283-294. H. Clay, J.M. Davis, D. Beery, A. Huttenlocher, S. E. Lyons and L. Ramakrishnan. 2007. Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish. Cell Host and Microbe 2:29-39. Medline database search for this researcher
Updated 12/21/10
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