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

Boston University
National Emerging Infectious Disease Lab

Boston University
Pulmonary Center

Boston University
Evans Center for Interdisciplinary Biomedical Research

Boston University
Genome Science Institute

Boston Medical Center

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

Necrosis in Pulmonary TB granulomas: dynamics, mechanisms, and therapies
03/04/2022 - 02/28/2026 (PI)
NIH/National Heart, Lung, and Blood Institute

Sideropher-depedent inhibitors of Mycobacterium tuberculosis
06/22/2020 - 05/31/2022 (Subcontract PI)
The University of Alabama at Birmingham NIH NIAID

Aberrant Immune activation in the tuberculous granuloma: a pivotal role in necrosis
07/15/2016 - 06/30/2021 (PI)
NIH/National Heart, Lung, and Blood Institute

Necrosis in Pulmonary TB granulomas: dynamics, mechanisms, therapies
05/01/2016 - 04/30/2021 (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 (Subcontract 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

National Emerging Infectious Diseases Laboratories Operations
06/20/2012 - 07/31/2014 (Sub-Project Level Key Person)
PI: John R. Murphy, PhD
NIH/National Institute of Allergy & Infectious Diseases

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

Showing 10 of 11 results. Show All Results

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


Yr Title Project-Sub Proj Pubs
2022 Necrosis in Pulmonary TB granulomas: dynamics, mechanisms, and therapies 2R01HL126066-05
2019 Aberrant immune activation in the tuberculosis granuloma: a pivotal role in necrosis 5R01HL133190-04 4
2019 Necrosis in pulmonary TB granulomas: dynamics, mechanisms, therapies 5R01HL126066-04 5
2018 Aberrant immune activation in the tuberculosis granuloma: a pivotal role in necrosis 5R01HL133190-03 4
2018 Necrosis in pulmonary TB granulomas: dynamics, mechanisms, therapies 5R01HL126066-03 5
2017 Aberrant immune activation in the tuberculosis granuloma: a pivotal role in necrosis 5R01HL133190-02 4
2017 Necrosis in pulmonary TB granulomas: dynamics, mechanisms, therapies 5R01HL126066-02 5
2017 Novel TB Treatment Strategy - Optimization of Macrophage Responsiveness to IFNy 5R33AI105944-05 4
2016 Aberrant immune activation in the tuberculosis granuloma: a pivotal role in necrosis 1R01HL133190-01 4
2016 Necrosis in pulmonary TB granulomas: dynamics, mechanisms, therapies 1R01HL126066-01A1 5
Showing 10 of 33 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.

iCite Analysis       Copy PMIDs To Clipboard

  1. Rosenbloom R, Gavrish I, Tseng AE, Seidel K, Yabaji SM, Gertje HP, Huber BR, Kramnik I, Crossland NA. Progression and Dissemination of Pulmonary Mycobacterium Avium Infection in a Susceptible Immunocompetent Mouse Model. Int J Mol Sci. 2022 May 26; 23(11).View Related Profiles. PMID: 35682679; PMCID: PMC9181083; DOI: 10.3390/ijms23115999;
  2. Yabaji SM, Chatterjee S, Waligursky E, Gimelbrant A, Kramnik I. Medium throughput protocol for genome-based quantification of intracellular mycobacterial loads and macrophage survival during in vitro infection. STAR Protoc. 2022 06 17; 3(2):101241. PMID: 35310069; PMCID: PMC8931439; DOI: 10.1016/j.xpro.2022.101241;
  3. Koyuncu D, Niazi MKK, Tavolara T, Abeijon C, Ginese ML, Liao Y, Mark C, Specht A, Gower AC, Restrepo BI, Gatti DM, Kramnik I, Gurcan M, Yener B, Beamer G. CXCL1: A new diagnostic biomarker for human tuberculosis discovered using Diversity Outbred mice. PLoS Pathog. 2021 08; 17(8):e1009773.View Related Profiles. PMID: 34403447; PMCID: PMC8423361; DOI: 10.1371/journal.ppat.1009773;
  4. Chatterjee S, Yabaji SM, Rukhlenko OS, Bhattacharya B, Waligurski E, Vallavoju N, Ray S, Kholodenko BN, Brown LE, Beeler AB, Ivanov AR, Kobzik L, Porco JA, Kramnik I. Channeling macrophage polarization by rocaglates increases macrophage resistance to Mycobacterium tuberculosis. iScience. 2021 Aug 20; 24(8):102845.View Related Profiles. PMID: 34381970; PMCID: PMC8333345; DOI: 10.1016/j.isci.2021.102845;
  5. Ji DX, Witt KC, Kotov DI, Margolis SR, Louie A, Chevée V, Chen KJ, Gaidt MM, Dhaliwal HS, Lee AY, Nishimura SL, Zamboni DS, Kramnik I, Portnoy DA, Darwin KH, Vance RE. Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons. Elife. 2021 06 21; 10. PMID: 34151776; PMCID: PMC8248984; DOI: 10.7554/eLife.67290;
  6. Ordonez AA, Tucker EW, Anderson CJ, Carter CL, Ganatra S, Kaushal D, Kramnik I, Lin PL, Madigan CA, Mendez S, Rao J, Savic RM, Tobin DM, Walzl G, Wilkinson RJ, Lacourciere KA, Via LE, Jain SK. Visualizing the dynamics of tuberculosis pathology using molecular imaging. J Clin Invest. 2021 03 01; 131(5). PMID: 33645551; PMCID: PMC7919721; DOI: 10.1172/JCI145107;
  7. Bhattacharya B, Xiao S, Chatterjee S, Urbanowski M, Ordonez A, Ihms EA, Agrahari G, Lun S, Berland R, Pichugin A, Gao Y, Connor J, Ivanov AR, Yan BS, Kobzik L, Koo BB, Jain S, Bishai W, Kramnik I. The integrated stress response mediates necrosis in murine Mycobacterium tuberculosis granulomas. J Clin Invest. 2021 02 01; 131(3).View Related Profiles. PMID: 33301427; PMCID: PMC7843230; DOI: 10.1172/JCI130319;
  8. Apt AS, Kramnik I, McMurray DN. Editorial: Mycobacteria-Host Interactions: Genetics, Immunity, Pathology. Front Cell Infect Microbiol. 2020; 10:611216. PMID: 33194847; PMCID: PMC7661744; DOI: 10.3389/fcimb.2020.611216;
  9. Gregory DJ, DeLoid GM, Salmon SL, Metzger DW, Kramnik I, Kobzik L. SON DNA-binding protein mediates macrophage autophagy and responses to intracellular infection. FEBS Lett. 2020 09; 594(17):2782-2799. PMID: 32484234; PMCID: PMC7708400; DOI: 10.1002/1873-3468.13851;
  10. Ji DX, Yamashiro LH, Chen KJ, Mukaida N, Kramnik I, Darwin KH, Vance RE. Publisher Correction: Type I interferon-driven susceptibility to Mycobacterium tuberculosis is mediated by IL-1Ra. Nat Microbiol. 2020 05; 5(5):777. PMID: 32300234
Showing 10 of 60 results. Show More

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

Bar chart showing 60 publications over 26 distinct years, with a maximum of 6 publications in 2012


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620 Albany St
Boston MA 02118
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