Igor Kramnik

Igor Kramnik

Associate Professor

Boston University, USA

Email: ikramnik@bu.edu






Network Investigator


Research Keywords: 

TB mouse animal model, macrophage, T cell



My lab and I have been studying mechanisms of host susceptibility to tuberculosis, pulmonary immunity and pulmonary TB pathology. Using mouse models of pulmonary TB, we have discovered a major genetic locus, sst1, that specifically controls the necrotization of pulmonary TB lesions. These studies provided mechanistic basis for the development of novel host-directed therapies that prevent necrosis within TB lesions. Recently, we started to develop a novel therapeutic strategy – sensitization of macrophage to IFN-gamma. We found that plant-derived and synthetic rocaglates enhance macrophage activation with IFNg, induce autophagy and block alternative macrophage activation. Currently, we explore their therapeutic potential in TB in combination with antibiotics and TB vaccination.


Related Websites: 

Profile page at Boston University Immunology Training Program


Key Publications:

Kramnik, I., Dietrich, W. F., Demant, P. & Bloom, B. R. Genetic control of resistance to experimental infection with virulent Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 97, 8560-8565, doi:10.1073/pnas.150227197 (2000).

Pan, H. et al. Ipr1 gene mediates innate immunity to tuberculosis. Nature 434, 767-772, doi:10.1038/nature03419 (2005).

Yan, B. S., Kirby, A., Shebzukhov, Y. V., Daly, M. J. & Kramnik, I. Genetic architecture of tuberculosis resistance in a mouse model of infection. Genes Immun 7, 201-210, doi:10.1038/sj.gene.6364288 (2006).

Yan, B. S. et al. Progression of pulmonary tuberculosis and efficiency of bacillus Calmette-Guerin vaccination are genetically controlled via a common sst1-mediated mechanism of innate immunity. J Immunol 179, 6919-6932 (2007).

Kramnik, I. Genetic dissection of host resistance to Mycobacterium tuberculosis: the sst1 locus and the Ipr1 gene. Curr Top Microbiol Immunol 321, 123-148 (2008).

Nalbandian, A., Yan, B. S., Pichugin, A., Bronson, R. T. & Kramnik, I. Lung carcinogenesis induced by chronic tuberculosis infection: the experimental model and genetic control. Oncogene 28, 1928-1938, doi:10.1038/onc.2009.32 (2009).

Pichugin, A. V., Yan, B. S., Sloutsky, A., Kobzik, L. & Kramnik, I. Dominant role of the sst1 locus in pathogenesis of necrotizing lung granulomas during chronic tuberculosis infection and reactivation in genetically resistant hosts. Am J Pathol 174, 2190-2201, doi:10.2353/ajpath.2009.081075 (2009).

Bhattacharya, B. et al. Fine-tuning of macrophage activation using synthetic rocaglate derivatives. Sci Rep 6, 24409, doi:10.1038/srep24409 (2016).

Kramnik, I. & Beamer, G. Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies. Semin Immunopathol 38, 221-237, doi:10.1007/s00281-015-0538-9 (2016).

Ji, D. X. et al. Type I interferon-driven susceptibility to Mycobacterium tuberculosis is mediated by IL-1Ra. Nat Microbiol 4, 2128-2135, doi:10.1038/s41564-019-0578-3 (2019).