Sunhee Lee, PhD
Research Interest: Host-Pathogen Interactions During Mycobacterium tuberculosis Infection
My laboratory’s focus concerns the study of the virulence factors and immune evasion strategies of Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). TB remains a major global health problem, despite the widespread use of the Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine and drug therapies. Additionally, coinfection of M. tuberculosis and HIV (TB/HIV), as well as multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, makes TB control even more difficult, complex and challenging. The long-term goal of my laboratory is the generation of safe and effective mycobacterial vaccines and therapeutics through the study, manipulation, and exploitation of mycobacterial proteins responsible for virulence and evasion of host immune responses.
Many lines of evidence indicate that M. tuberculosis has evolved mechanisms to evade host immunity, in some cases by inhibiting the priming and effector functions of various T cell subsets. Cell death pathways are central to the interaction between pathogenic mycobacteria and host macrophages. The inhibition of cell death of infected host cells is a well documented, but poorly understood, function of pathogenic mycobacteria. Several advantages may accrue to mycobacteria as a result of delaying or inhibiting macrophage cell death, including preservation of a protected growth environment, prevention of intrinsic microbicidal activities in the host cell, and reduced stimulation of protective immunity. The genetic basis for this anti-cell death phenotype has not been fully elucidated. Using a M. tuberculosis transposon mutant library, we screened pro-cell death mutants of M. tuberculosis and found multiple genetic loci that are responsible for inhibiting infection-induced cell death of macrophages. My lab studies these genes in relation to virulence and immunogenicity of pathogenic mycobacteria. We seek to identify key components of the genetic basis for important virulence traits of mycobacteria, thereby providing the tools necessary to investigate the details of this host-pathogen interaction.
- Cronan MR, Beerman RW, Rosenberg AF, Saelens JW, Johnson MG, Oehlers SH, Sisk DM, Jurcic Smith KL, Medvitz NA, Miller SE, Trinh LA, Fraser SE, Madden JF, Turner J, Stout JE, Lee S, Tobin DM. 2016. Macrophage epithelial reprogramming underlies mycobacterial granuloma formation and promotes infection. Immunity. 45:861-876.
Hongjie Pan, Xiao-ping Zhong, and Sunhee Lee. 2016. Sustained Activation of mTORC1 Increases Resistance to Active Tuberculosis through AMPKα-dependent Autophagy Activation. BMC Biochem. 17:14.
Smith K and Lee S. 2016. Enhanced cell death and immunogenicity induced by tuberculosis deletion mutant of Rv2456c. Int. J. Mycobacteriol. In press. http://dx.doi/10.1016/j.ijmyco.2016.06.018
Hart B, Hale L, and Lee S. 2016. Immunogenicity and protection conferred by a recombinant Mycobacterium marinum vaccine against Buruli ulcer. Trials in 5:88-91.
Hart B, Hale L, and Lee S. 2015. Recombinant BCG Expressing Mycobacterium ulcerans Ag85A imparts enhanced protection against experimental Buruli ulcer. PLoS Negl Trop Dis. 22;9(9):e0004046.
Korioth-Schmitz B, Perley CC, Sixsmith JD, Click EM, Lee S, Letvin NL, Frothingham R. 2015. Rhesus immune responses to SIV Gag expressed by recombinant BCG vectors are independent from pre-existing mycobacterial immunity. Vaccine. 33(42): 5715-22.
Mark R. Cronan, Allison F. Rosenberg, Stefan H. Oehlers, Joseph W. Saelens, Dana M. Sisk, Kristen L. Jurcic Smith, Sunhee Lee, David M. Tobin. 2015. CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections. Disease Models and Mechanisms. 8:1643-1650
Bryan Hart, Rose Asrican, So-Yon Lim, Jaimie Sixsmith, Regy Lukose, Sommer Souther, Swati Rayasam, Joseph Saelens, Ching-ju Chen, Sarah Seay, Linda Berney-Meyer, Leslie Magtanong, Kim Vermeul, Priyadharshini Pajanirassa, Amanda Jimenez, Tony Ng, David Tobin, Steven Porcelli, Michelle Larsen, Joern Schmitz, Barton Haynes, William Jacobs, Sunhee Lee*, and Richard Frothingham*. 2015. Stable Expression of Lentiviral Antigens by Quality-Controlled Recombinant BCG Vectors. Clin Vaccine Immunol. 22 (7): 726-741. (*co-senior authors)
Smith KJ, Saini D, Bardarov S, Larsen M, Frothingham R, Gandhi R, Jacobs WRJ, Sturm AW, Lee S. 2014. Reduced virulence of an Extensively drug-resistant outbreak strain of Mycobacterium
tuberculosis in a murine model. PLoS One. 9(4): e94953.
Zullo AJ, Smith KJ, Lee S. 2014. Mammalian target of Rapamycin inhibition and mycobacterial survival are uncoupled in murine macrophages. BMC Biochemistry. 15:4.
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