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Assistant Professor, Division of Infectious Diseases
My primary interest lies in the genes essential for growth of mycobacteria in vivo an in vitro. These genes likely code for proteins with essential function. We have created a library of transposon insertion mutants of M. tuberculosis Oshkosh CDC1551 strain and directly identified non-essential genes. These genes, when inactivated by transposon insertion did not compromise the growth of the bacillus in vitro. Currently we are trying to find genes whose functions are required for survival and growth in vivo in the mouse model of tuberculosis. These genes would be rational targets for new anti-tuberculosis drugs. Or, when these genes are modified, the resulting strains are likely to be attenuated in growth and virulence. This phenotype would be suitable for studying vaccine development.
In the future I intend to study the mechanism of cell division and the regulation of cell cycle in Mycobacteria.
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1. Converse, P. J., P. C. Karakousis, L. G. Klinkenberg, A. K. Kesavan, L. H. Ly, S. S. Allen, J. H. Grosset, S. K. Jain, G. Lamichhane, Y. C. Manabe, D. N. McMurray, E. L. Nuermberger, and W. R. Bishai. 2009. Role of the dosR-dosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models. Infect Immun 77:1230-7.
2. Alahari, A., L. Alibaud, X. Trivelli, R. Gupta, G. Lamichhane, R. C. Reynolds, W. R. Bishai, Y. Guerardel, and L. Kremer. 2009. Mycolic acid methyltransferase, MmaA4, is necessary for thiacetazone susceptibility in Mycobacterium tuberculosis. Mol Microbiol 71:1263-77.
3. Be, N. A., G. Lamichhane, J. Grosset, S. Tyagi, Q. J. Cheng, K. S. Kim, W. R. Bishai, and S. K. Jain. 2008. Murine model to study the invasion and survival of Mycobacterium tuberculosis in the central nervous system. J Infect Dis 198:1520-8.
4. Lamichhane, G., and W. Bishai. 2007. Defining the 'survivasome' of Mycobacterium tuberculosis. Nat Med 13:280-2.
5. Jain, S. K., S. M. Hernandez-Abanto, Q. J. Cheng, P. Singh, L. H. Ly, L. G. Klinkenberg, N. E. Morrison, P. J. Converse, E. Nuermberger, J. Grosset, D. N. McMurray, P. C. Karakousis, G. Lamichhane, and W. R. Bishai. 2007. Accelerated detection of Mycobacterium tuberculosis genes essential for bacterial survival in guinea pigs, compared with mice. J Infect Dis 195:1634-42.
6. Lamichhane, G., T. R. Raghunand, N. E. Morrison, S. C. Woolwine, S. Tyagi, K. Kandavelou, and W. R. Bishai. 2006. Deletion of a Mycobacterium tuberculosis Proteasomal ATPase Homologue Gene Produces a Slow-Growing Strain That Persists in Host Tissues. J Infect Dis 194:1233-40.
7. Jain, S. K., M. Paul-Satyaseela, G. Lamichhane, K. S. Kim, and W. R. Bishai. 2006. Mycobacterium tuberculosis invasion and traversal across an in vitro human blood-brain barrier as a pathogenic mechanism for central nervous system tuberculosis. J Infect Dis 193:1287-95.
8. Lamichhane, G., S. Tyagi, and W. R. Bishai. 2005. Designer arrays for defined mutant analysis to detect genes essential for survival of Mycobacterium tuberculosis in mouse lungs. Infect Immun 73:2533-40.
9. Karakousis, P. C., T. Yoshimatsu, G. Lamichhane, S. C. Woolwine, E. L. Nuermberger, J. Grosset, and W. R. Bishai. 2004. Dormancy phenotype displayed by extracellular Mycobacterium tuberculosis within artificial granulomas in mice. J Exp Med 200:647-57.
10. Lamichhane, G., M. Zignol, N. J. Blades, D. E. Geiman, A. Dougherty, J. Grosset, K. W. Broman, and W. R. Bishai. 2003. A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: application to Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 100:7213-8.
