Gyanu Lamichhane, PhD

Dr. Gyanu Lamichhane

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.

To read some of these publications online, click here. Please note that to read the full text of some of these articles requires that you have an online subscription to the journal.

1: Lamichhane G, Freundlich JS, Ekins S, Wickramaratne N, Nolan ST, Bishai WR. Essential Metabolites of Mycobacterium tuberculosis and Their Mimics. MBio. 2011 Feb 1;2(1). pii: e00301-10. doi: 10.1128/mBio.00301-10. PubMed: 21285434;

2: Wolschendorf F, Ackart D, Shrestha TB, Hascall-Dove L, Nolan S, Lamichhane G, Wang Y, Bossmann SH, Basaraba RJ, Niederweis M. Copper resistance is essential for virulence of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1621-6. Epub 2011 Jan 4. PubMed: 21205886.

3: Lamichhane G. Novel targets in M. tuberculosis: search for new drugs. Trends Mol Med. 2010 Nov 9. [Epub ahead of print] PubMed: 21071272.

4: Nolan ST, Lamichhane G. Protective efficacy of BCG overexpressing an L,D-transpeptidase against M. tuberculosis infection. PLoS One. 2010 Oct 29;5(10):e13773. PubMed : 21048936; : PMC2966435.

5: Converse PJ, Eisenach KD, Theus SA, Nuermberger EL, Tyagi S, Ly LH, Geiman DE, Guo H, Nolan ST, Akar NC, Klinkenberg LG, Gupta R, Lun S, Karakousis PC, Lamichhane G, McMurray DN, Grosset JH, Bishai WR. The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models. PLoS One. 2010 Apr 21;5(4):e10289. PubMed 20422019

6: Dutta NK, Mehra S, Didier PJ, Roy CJ, Doyle LA, Alvarez X, Ratterree M, Be NA, Lamichhane G, Jain SK, Lacey MR, Lackner AA, Kaushal D. Genetic requirements for the survival of tubercle bacilli in primates. J Infect Dis. 2010 Jun 1;201(11):1743-52. PubMed: 20394526.

7: Gupta R, Lavollay M, Mainardi JL, Arthur M, Bishai WR, Lamichhane G. The Mycobacterium tuberculosis protein LdtMt2 is a nonclassical transpeptidase required for virulence and resistance to amoxicillin. Nat Med. 2010 Apr;16(4):466-9. Epub 2010 Mar 21. PubMed: 20305661.

8: Olaleye O, Raghunand TR, Bhat S, He J, Tyagi S, Lamichhane G, Gu P, Zhou J, Zhang Y, Grosset J, Bishai WR, Liu JO. Methionine aminopeptidases from Mycobacterium tuberculosis as novel antimycobacterial targets. Chem Biol. 2010 Jan 29;17(1):86-97. PubMed : 20142044.

9: Davis SL, Be NA, Lamichhane G, Nimmagadda S, Pomper MG, Bishai WR, Jain SK. Bacterial thymidine kinase as a non-invasive imaging reporter for Mycobacterium tuberculosis in live animals. PLoS One. 2009 Jul 16;4(7):e6297. PubMed :19606217.

10: Agarwal N, Lamichhane G, Gupta R, Nolan S, Bishai WR. Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase. Nature. 2009 Jul 2;460(7251):98-102. Epub 2009 Jun 10. PubMed : 19516256.

11: Alahari A, Alibaud L, Trivelli X, Gupta R, Lamichhane G, Reynolds RC, Bishai WR, Guerardel Y, Kremer L. Mycolic acid methyltransferase, MmaA4, is necessary for thiacetazone susceptibility in Mycobacterium tuberculosis. Mol Microbiol. 2009 Mar;71(5):1263-77. Epub 2009 Jan 15. PubMed : 19183278.

12: Converse PJ, Karakousis PC, Klinkenberg LG, Kesavan AK, Ly LH, Allen SS, Grosset JH, Jain SK, Lamichhane G, Manabe YC, McMurray DN, Nuermberger EL, Bishai WR. Role of the dosR-dosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models. Infect Immun. 2009 Mar;77(3):1230-7. Epub 2008 Dec 22. PubMed: 19103767.

13: Be NA, Lamichhane G, Grosset J, Tyagi S, Cheng QJ, Kim KS, Bishai WR, Jain SK. Murine model to study the invasion and survival of Mycobacterium tuberculosis in the central nervous system. J Infect Dis. 2008 Nov 15;198(10):1520-8. Erratum in: J Infect Dis. 2009 Jan 15;199(2):290. PubMed : 18956986.

14: Jain SK, Hernandez-Abanto SM, Cheng QJ, Singh P, Ly LH, Klinkenberg LG, Morrison NE, Converse PJ, Nuermberger E, Grosset J, McMurray DN, Karakousis PC, Lamichhane G, Bishai WR. Accelerated detection of Mycobacterium tuberculosis genes essential for bacterial survival in guinea pigs, compared with mice. J Infect Dis. 2007 Jun 1;195(11):1634-42. Epub 2007 Apr 23. PubMed : 17471433.

15: Lamichhane G, Bishai W. Defining the 'survivasome' of Mycobacterium tuberculosis. Nat Med. 2007 Mar;13(3):280-2. PubMed : 17342137.

16: Lamichhane G, Raghunand TR, Morrison NE, Woolwine SC, Tyagi S, Kandavelou K, Bishai WR. Deletion of a Mycobacterium tuberculosis proteasomal ATPase homologue gene produces a slow-growing strain that persists in host tissues. J Infect Dis. 2006 Nov 1;194(9):1233-40. Epub 2006 Oct 2. PubMed : 17041849.

17: Jain SK, Paul-Satyaseela M, Lamichhane G, Kim KS, Bishai WR. 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. 2006 May 1;193(9):1287-95. Epub 2006 Mar 28. PubMed : 16586367.

18: Lamichhane G, Tyagi S, Bishai WR. Designer arrays for defined mutant analysis to detect genes essential for survival of Mycobacterium tuberculosis in mouse lungs. Infect Immun. 2005 Apr;73(4):2533-40. PubMed : 15784600.

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