Faculty

Lalita Ramakrishnan, MD, PhD

• Professor of Microbiology, Medicine and Immunology
• University of Washington

Our laboratory studies the pathogenesis of tuberculosis and is interested in the host and pathogen contributions to mycobacterial persistence which is accompanied by the development and maintenance of granulomatous infection. We study Mycobacterium marinum, a human and fish pathogen (and a close genetic relative of M. tuberculosis) in its natural host the zebrafish. The developing zebrafish is an ideal model host as it is optically transparent and amenable to genetics and small molecule screens. We can view in real-time the cellular events leading to granuloma formation and assess the contribution of individual host and pathogen determinants to discrete steps in the process. We have identified new host determinants that impact susceptibility to tuberculosis by conducting forward genetic screens. Similarly, we are trying to understand bacterial virulence determinants and determinants of long-term persistence by using bacterial mutants and inducible fluorescence reporters again taking advantage or our unique animal models. We have developed the zebrafish as a platform for tuberculous drug discovery. Finally, we find that the zebrafish can also be used as a model organism to study other bacterial pathogens.

Selected Publications

Davis JM, Haake DA, Ramakrishnan L. Leptospira interrogans stably infects zebrafish embryos, altering phagocyte behavior and homing to specific tissues. PLoS Negl Trop Dis. 2009 Jun 23;3(6):e463.
[ PubMed Abstract ]

Brannon MK, Davis JM, Mathias JR, Hall CJ, Emerson JC, Crosier PS, Huttenlocher A, Ramakrishnan L, Moskowitz SM. Pseudomonas aeruginosa Type III secretion system interacts with phagocytes to modulate systemic infection of zebrafish embryos. Cell Microbiol, 2009 Feb 6; 11:755-768
[ PubMed Abstract ]

Davis JM, Ramakrishnan L. The role of the granuloma in the expansion and dissemination of early tuberculous infection. Cell. 2009 Jan 9;136(1):37-49.
[ PubMed Abstract ]

Clay H, Volkman HE, Ramakrishnan L. Tumor necrosis factor signaling mediates resistance to mycobacteria by inhibiting bacterial growth and macrophage death. Immunity. 2008 Aug 15;29(2):283-94.
[ PubMed Abstract ]

Connolly LE, Edelstein PH, Ramakrishnan L. Why is long-term therapy required to cure tuberculosis? PLoS Med. 2007 Mar;4(3):e120.
[ PubMed Abstract ]

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