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Faculty

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Lalita Ramakrishnan, MD, PhD

  • Professor, Departments 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. We are now also translating our basic laboratory findings to the clinic to improve the treatment of TB.


Selected Publications


Roca FJ, Ramakrishnan L. TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell. 2013; 153(3): 521-34.
PubMed Abstract


Ramakrishnan L. Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol. 2012; 12: 352-66.
• PubMed Abstract


Tobin DM, Roca RJ, Oh SF, McFarland R, Vickery TW, Ray JP, Ko DC, Zou Y, Bang ND, Chau TT, Vary JC, Hawn TR, Dunstan SJ, Farrar JJ, Thwaites GE, King MC, Serhan CN, Ramakrishnan L. Host genotype directed therapies can optimize the inflammatory response to mycobacterial infections. Cell. 2012; 148: 434-46.
PubMed Abstract


Volkman HE, Pozos TC, Zheng J, Davis JM, Rawls JF, Ramakrishnan L. Tuberculous granuloma induction via interactions of a bacterial secreted protein with host epithelium. Science. 2010; 327: 466-9.
Science Magazine Abstract


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


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