Igor Kramnik, MD, PhD
Associate Professor
Boston University School of Medicine
Dept of Medicine
Pulmonary, Allergy, Sleep & Critical Care Medicine

MD, Samara State Medical University
PhD, Russian Academy of Medical Sciences

Control of tuberculosis (TB) remains a global health priority despite a significant decrease in its prevalence within the past century. New challenges have emerged with the appearance of drug resistant forms of M.tb and the realization that the existing BCG vaccine is not sufficiently effective to eradicate the disease. Thus, the emergence and spread of drug resistant forms of Mycobacterium tuberculosis (M.tb) represents a significant global threat of re-emerging epidemics of TB with no effective therapies in sight.. Given the dearth of new drugs targeting the pathogen, interventions targeting host cells are urgently needed. However, our limited understanding of the virulence stragegy of M.tb remains a major obstacle to its complete eradication. In our view two major gaps exist on the host side: what makes some immunocompetent individuals more susceptible to M.tb than the majority of the population, and what makes the lungs an organ that is particularly vulnerable to M.tb. The lung is central to the virulence strategy of M.tb, because aerosol is the only epidemiologically significant route of M.tb transmission in human populations. Interventions that target the lung to enhance mechanisms of local immunity and prevent lung damage may produce the biggest epidemiological impact by preventing M.tb transmission.

We pursue identification of pathways exploited by the pathogen in the lungs of susceptible individuals – a critical node in the extremely successful evolutionary strategy of M.tb - and the development of targeted interventions. Our lab and collaborators described a novel mouse model of human-like pulmonary tuberculosis. The key element of this model is the development of well organized necrotic granulomas, which closely resemble the human disease, specifically in the lungs of otherwise immunocompetent mice. Using forward genetic analysis we identifed the sst1 locus as the one responsible for necrotization of the lung granulomas and identified the candidate gene Ipr1 using positional cloning. We have found that the Ipr1 protein is an interferon-inducible chromatin-associated protein involved in control of macrophage activation and death. Our current efforts are focused on understanding the Ipr1-mediated biochemical pathways and their role in host resistance to infections, control of lung inflammation and tissue damage. In addition we have developed a screening strategy to identify compounds that enhance the Ipr1 function, which can be developed into novel drugs that increase host resistance to M.tuberculosis and related infections.

During the course of these studies we documented the development of lung squamous cell carcinomas (SSC) at the chronic stages of tuberculosis infection. Because squamous cell carcinomas do not occur in our mouse strains spontaneously, we concluded that M.tb infection was sufficient for both initiation and progression of lung SCC. These findings experimentally proved a causal link between tuberculosis and lung cancers, recently confirmed by epidemiological analysis in humans. Thus the TB-infected lung presents a destabilizing environment for epithelial cells, yet factors influencing epithelial cell function in the context of chronic infection have not been much studied. We study lung epithelial cells over the course of TB infection to understand mechanisms of their injury, repair, and neoplastic transformation in order to develop interventions that restore epithelial cell homeostasis and prevent initiation of lung tumors during TB progression.

Associate Professor
Boston University School of Medicine

Center Faculty Member
Boston University School of Medicine
Pulmonary Center

Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Division of Graduate Medical Sciences

Boston Medical Center

Aberrant Immune activation in the tuberculous granuloma: a pivotal role in necrosis
07/15/2016 - 06/30/2020 (PI)
NIH/National Heart, Lung, and Blood Institute

Necrosis in Pulmonary TB granulomas: dynamics, mechanisms, therapies
05/01/2016 - 04/30/2020 (PI)
NIH/National Heart, Lung, and Blood Institute

Novel TB Treatment Strategy - Optimization of Macrophage Responsiveness to IFNy
03/11/2015 - 02/28/2019 (PI)
NIH/National Institute of Allergy & Infectious Diseases

Genetic-based susceptibility to pulmonary tuberculosis
04/15/2015 - 03/31/2018 (PI)
Trustees of Tufts College, Inc NIH NIAID

Novel TB Treatment Strategy- Optimization of Macrophage Responsiveness to IFNy
03/01/2013 - 02/28/2015 (PI)
NIH/National Institute of Allergy & Infectious Diseases

Genetics of Host Resistance and Susceptibility to MTB
08/01/2012 - 07/31/2014 (PI)
NIH/National Heart, Lung, and Blood Institute

09/17/2010 - 05/31/2013 (PI)
Harvard School of Public Health DOD DARPA

Macrophage Genomic ‘Barcodes’ for Rapid Identification of Pathogens and Therapeutic Targets
09/17/2010 - 05/31/2013 (PI)
Harvard School of Public Health DOD Threat Reduction

Genetics of Host resistance & susceptibility to MTB
08/01/2009 - 08/02/2012 (PI)
5R01 HL059836-15

Yr Title Project-Sub Proj Pubs
2018 Aberrant immune activation in the tuberculosis granuloma: a pivotal role in necrosis 5R01HL133190-03
2018 Necrosis in pulmonary TB granulomas: dynamics, mechanisms, therapies 5R01HL126066-03
2017 Necrosis in pulmonary TB granulomas: dynamics, mechanisms, therapies 5R01HL126066-02
2017 Novel TB Treatment Strategy - Optimization of Macrophage Responsiveness to IFNy 5R33AI105944-05
2016 Aberrant immune activation in the tuberculosis granuloma: a pivotal role in necrosis 1R01HL133190-01
2016 Necrosis in pulmonary TB granulomas: dynamics, mechanisms, therapies 1R01HL126066-01A1
2015 Novel TB Treatment Strategy - Optimization of Macrophage Responsiveness to IFNy 4R33AI105944-03
2014 Novel TB Treatment Strategy - Optimization of Macrophage Responsiveness to IFNy 5R21AI105944-02 1
2013 Novel TB Treatment Strategy - Optimization of Macrophage Responsiveness to IFNy 1R21AI105944-01 1
2013 Aerobiology 3UC7AI070088-05S3-6799 1
Showing 10 of 28 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Gregory DJ, Kramnik I, Kobzik L. Protection of macrophages from intracellular pathogens by miR-182-5p mimic-a gene expression meta-analysis approach. FEBS J. 2018 Jan; 285(2):244-260. PMID: 29197182.
  2. Coleman FT, Blahna MT, Kamata H, Yamamoto K, Zabinski MC, Kramnik I, Wilson AA, Kotton DN, Quinton LJ, Jones MR, Pelton SI, Mizgerd JP. Capacity of Pneumococci to Activate Macrophage Nuclear Factor ?B: Influence on Necroptosis and Pneumonia Severity. J Infect Dis. 2017 Aug 15; 216(4):425-435.View Related Profiles. PMID: 28368460; DOI: 10.1093/infdis/jix159;.
  3. Leu JS, Chen ML, Chang SY, Yu SL, Lin CW, Wang H, Chen WC, Chang CH, Wang JY, Lee LN, Yu CJ, Kramnik I, Yan BS. SP110b Controls Host Immunity and Susceptibility to Tuberculosis. Am J Respir Crit Care Med. 2017 Feb 01; 195(3):369-382. PMID: 27858493; DOI: 10.1164/rccm.201601-0103OC;.
  4. Coppola M, van Meijgaarden KE, Franken KL, Commandeur S, Dolganov G, Kramnik I, Schoolnik GK, Comas I, Lund O, Prins C, van den Eeden SJ, Korsvold GE, Oftung F, Geluk A, Ottenhoff TH. New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles. Sci Rep. 2016 11 28; 6:37793. PMID: 27892960; DOI: 10.1038/srep37793;.
  5. Bhattacharya B, Chatterjee S, Devine WG, Kobzik L, Beeler AB, Porco JA, Kramnik I. Fine-tuning of macrophage activation using synthetic rocaglate derivatives. Sci Rep. 2016 Apr 18; 6:24409.View Related Profiles. PMID: 27086720; PMCID: PMC4834551; DOI: 10.1038/srep24409;.
  6. 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. 2016 Mar; 38(2):221-37. PMID: 26542392; PMCID: PMC4779126; DOI: 10.1007/s00281-015-0538-9;.
  7. Niazi MK, Dhulekar N, Schmidt D, Major S, Cooper R, Abeijon C, Gatti DM, Kramnik I, Yener B, Gurcan M, Beamer G. Lung necrosis and neutrophils reflect common pathways of susceptibility to Mycobacterium tuberculosis in genetically diverse, immune-competent mice. Dis Model Mech. 2015 Sep; 8(9):1141-53. PMID: 26204894; PMCID: PMC4582107; DOI: 10.1242/dmm.020867;.
  8. Irwin SM, Gruppo V, Brooks E, Gilliland J, Scherman M, Reichlen MJ, Leistikow R, Kramnik I, Nuermberger EL, Voskuil MI, Lenaerts AJ. Limited activity of clofazimine as a single drug in a mouse model of tuberculosis exhibiting caseous necrotic granulomas. Antimicrob Agents Chemother. 2014 Jul; 58(7):4026-34. PMID: 24798275; PMCID: PMC4068578; DOI: 10.1128/AAC.02565-14;.
  9. He X, Berland R, Mekasha S, Christensen TG, Alroy J, Kramnik I, Ingalls RR. The sst1 resistance locus regulates evasion of type I interferon signaling by Chlamydia pneumoniae as a disease tolerance mechanism. PLoS Pathog. 2013; 9(8):e1003569.View Related Profiles. PMID: 24009502; PMCID: PMC3757055; DOI: 10.1371/journal.ppat.1003569;.
  10. Commandeur S, van Meijgaarden KE, Prins C, Pichugin AV, Dijkman K, van den Eeden SJ, Friggen AH, Franken KL, Dolganov G, Kramnik I, Schoolnik GK, Oftung F, Korsvold GE, Geluk A, Ottenhoff TH. An unbiased genome-wide Mycobacterium tuberculosis gene expression approach to discover antigens targeted by human T cells expressed during pulmonary infection. J Immunol. 2013 Feb 15; 190(4):1659-71. PMID: 23319735; DOI: 10.4049/jimmunol.1201593;.
Showing 10 of 47 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 47 publications over 22 distinct years, with a maximum of 6 publications in 2012

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620 Albany St
Boston MA 02118
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