Shichun Lun, PhD
My research interests focus on the following three aspects:  genetic basis for tuberculosis pathogenesis;  synthetic lethal effects of gene-compound and/or compound-compound combinations; and  development of new anti-mycobacterial drugs and host-directed chemotherapeutics for tuberculosis. With more than 4,000 genes in Mycobacterium tuberculosis, the causative agent for human tuberculosis, the molecular mechanisms of pathogenesis could be partially studied by genetic knock-out and complementation and studying the gene functions both in vitro (biochemical) and in vivo using the well established mouse aerosol infection models. Because of the complexity of Mtb genetics, single pathway blockage usually results in suboptimal killing and higher frequency for the emergence of MDR- and XDR-TB. Combination of either gene-compound or compound-compound blocking two molecular pathways may shine a light on TB control and therapy. While development of pathogen-directed new anti-TB drugs is important and ongoing, the alternative of host-directed chemotherapeutics is an important complementation. Compounds that possess minimal or no activity on mycobacteria but are helping in controlling TB in vivo are being characterized and the mechanisms of action are under investigation.
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1: Pieroni M, Tipparaju SK, Lun S, Song Y, Sturm AW, Bishai WR, Kozikowski AP. Pyrido[1,2-a]benzimidazole-Based Agents Active Against Tuberculosis (TB), Multidrug-Resistant (MDR) TB and Extensively Drug-Resistant (XDR) TB. ChemMedChem. 2011 Feb 7;6(2):334-42. doi: 10.1002/cmdc.201000490. Epub 2011 Jan 21. PubMed : 21259445.
2: Nisa S, Blokpoel MC, Robertson BD, Tyndall JD, Lun S, Bishai WR, O'Toole R. Targeting the chromosome partitioning protein ParA in tuberculosis drug discovery. J Antimicrob Chemother. 2010 Nov;65(11):2347-58. Epub 2010 Sep 1. PubMed : 20810423;.
3: 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
4: Maloney E, Stankowska D, Zhang J, Fol M, Cheng QJ, Lun S, Bishai WR, Rajagopalan M, Chatterjee D, Madiraju MV. The two-domain LysX protein of Mycobacterium tuberculosis is required for production of lysinylated phosphatidylglycerol and resistance to cationic antimicrobial peptides. PLoS Pathog. 2009 Jul;5(7):e1000534. Epub 2009 Jul 31. PubMed : 19649276.
5: Nedeltchev GG, Raghunand TR, Jassal MS, Lun S, Cheng QJ, Bishai WR. Extrapulmonary dissemination of Mycobacterium bovis but not Mycobacterium tuberculosis in a bronchoscopic rabbit model of cavitary tuberculosis. Infect Immun. 2009 Feb;77(2):598-603. Epub 2008 Dec 8. PubMed : 19064634.
6: Lun S, Bishai WR. Characterization of a novel cell wall-anchored protein with carboxylesterase activity required for virulence in Mycobacterium tuberculosis. J Biol Chem. 2007 Jun 22;282(25):18348-56. Epub 2007 Apr 11. PubMed : 17428787.
7: Lun S, Aström G, Magnusson U, Ostensson K. Total and differential leucocyte counts and lymphocyte subpopulations in lymph, afferent and efferent to the supramammary lymph node, during endotoxin-induced bovine mastitis. Reprod Domest Anim. 2007 Apr;42(2):126-34. PubMed : 17348968.
8: Lun S, Willson PJ. Putative mannose-specific phosphotransferase system component IID represses expression of suilysin in serotype 2 Streptococcus suis. Vet Microbiol. 2005 Feb 25;105(3-4):169-80. Epub 2004 Dec 24. PubMed : 15708813.
9: Lun S, Willson PJ. Expression of green fluorescent protein and its application in pathogenesis studies of serotype 2 Streptococcus suis. J Microbiol Methods. 2004 Mar;56(3):401-12. PubMed : 14967232.
10: Lun S, Perez-Casal J, Connor W, Willson PJ. Role of suilysin in pathogenesis of Streptococcus suis capsular serotype 2. Microb Pathog. 2003 Jan;34(1):27-37. PubMed : 12620382.
11: Persson Waller K, Colditz IG, Lun S, Ostensson K. Cytokines in mammary lymph and milk during endotoxin-induced bovine mastitis. Res Vet Sci. 2003 Feb;74(1):31-6. PubMed : 12507564.