Lalita Ramakrishnan, M.B.B.S., Ph.D.
Professor, Microbiology and Medicine
Adjunct Professor, Immunology
Department of Microbiology
University of Washington
Phone:(206) 616-4286, (206) 221-6367
Office Location: K-443C HSC
Campus Box: 357242
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 where she developed Mycobacterium marinum as a model for tuberculosis working with Stanley Falkow. 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 antibiotic tolerance. The zebrafish model has helped to uncover fundamental mechanisms of mycobacterial virulence factors, host susceptibility determinants and mechanisms of antibiotic tolerance.
To understand the mechanistic basis of mycobacterial pathogenesis, , 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 bacterium and the zebrafish to monitor the infection process in real-time and modulate it using genetically defined host and bacterial mutants. Findings made in the zebrafish have been borne out in human populations and are informing new strategies for intervention.
Adams, K.N., Takaki, K.K., Connolly, L.E., Wiedenhoft, H, Winglee, K, Humbert, O., Edelstein, P.E., Cosma, C.L., Ramakrishnan, L. (2011). Drug Tolerance in Replicating Mycobacteria Induced by a Macrophage-Induced Efflux Mechanism. Cell, 145, 39-53
D. M. Tobin, J.C. 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.