Igor Kramnik, MD, PhD
Associate Professor
Boston University Chobanian & Avedisian School of Medicine
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 Chobanian & Avedisian School of Medicine
Virology, Immunology & Microbiology


Faculty
Boston University
National Emerging Infectious Disease Lab


Member
Boston University
Pulmonary Center


Member
Boston University
Evans Center for Interdisciplinary Biomedical Research


Member
Boston University
Genome Science Institute


Boston Medical Center


Graduate Faculty (Primary Mentor of Grad Students)
Boston University Chobanian & Avedisian 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
5R01HL126066-06

Sideropher-depedent inhibitors of Mycobacterium tuberculosis
06/22/2020 - 05/31/2022 (Subcontract PI)
University of Alabama at Birmingham NIH NIAID
5R21AI153981-02

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
5R01HL133190-04

Necrosis in Pulmonary TB granulomas: dynamics, mechanisms, therapies
05/01/2016 - 04/30/2021 (PI)
NIH/National Heart, Lung, and Blood Institute
5R01HL126066-04

Novel TB Treatment Strategy - Optimization of Macrophage Responsiveness to IFNy
03/11/2015 - 02/28/2019 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5R33AI105944-05

Genetic-based susceptibility to pulmonary tuberculosis
04/15/2015 - 03/31/2018 (Subcontract PI)
Trustees of Tufts College, Inc NIH NIAID
5R21AI115038-02

Novel TB Treatment Strategy- Optimization of Macrophage Responsiveness to IFNy
03/01/2013 - 02/28/2015 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5R21AI105944-02

Genetics of Host Resistance and Susceptibility to MTB
08/01/2012 - 07/31/2014 (PI)
NIH/National Heart, Lung, and Blood Institute
7R01HL059836-16

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
3UC7AI070088-05S3

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)
NIH-NHLBI
5R01 HL059836-15


Title


Yr Title Project-Sub Proj Pubs
2024 Necrosis in Pulmonary TB granulomas: dynamics, mechanisms, and therapies 5R01HL126066-07
2023 Necrosis in Pulmonary TB granulomas: dynamics, mechanisms, and therapies 5R01HL126066-06
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
Showing 10 of 35 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. Yabaji SM, Zhernovkov V, Araveti PB, Lata S, Rukhlenko OS, Abdullatif SA, Alekseev Y, Ma Q, Dayama G, Lau NC, Bishai WR, Crossland NA, Campbell JD, Kholodenko BN, Gimelbrant AA, Kobzik L, Kramnik I. Myc Dysregulation in Activated Macrophages Initiates Iron-Mediated Lipid Peroxidation that Fuels Type I Interferon and Compromises TB Resistance. bioRxiv. 2024 Mar 10.View Related Profiles. PMID: 38496444; PMCID: PMC10942339; DOI: 10.1101/2024.03.05.583602;
     
  2. Amaral EP, Namasivayam S, Queiroz ATL, Fukutani E, Hilligan KL, Aberman K, Fisher L, Bomfim CCB, Kauffman K, Buchanan J, Santuo L, Gazzinelli-Guimaraes PH, Costa DL, Teixeira MA, Barreto-Duarte B, Rocha CG, Santana MF, Cordeiro-Santos M, Barber DL, Wilkinson RJ, Kramnik I, Igarashi K, Scriba T, Mayer-Barber KD, Andrade BB, Sher A. BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility. Nat Microbiol. 2024 Jan; 9(1):120-135. PMID: 38066332; PMCID: PMC10769877; DOI: 10.1038/s41564-023-01523-7;
     
  3. Yabaji SM, Rukhlenko OS, Chatterjee S, Bhattacharya B, Wood E, Kasaikina M, Kholodenko BN, Gimelbrant AA, Kramnik I. Cell state transition analysis identifies interventions that improve control of Mycobacterium tuberculosis infection by susceptible macrophages. Sci Adv. 2023 Sep 29; 9(39):eadh4119.View Related Profiles. PMID: 37756395; PMCID: PMC10530096; DOI: 10.1126/sciadv.adh4119;
     
  4. Klever AM, Alexander KA, Almeida D, Anderson MZ, Ball RL, Beamer G, Boggiatto P, Buikstra JE, Chandler B, Claeys TA, Concha AE, Converse PJ, Derbyshire KM, Dobos KM, Dupnik KM, Endsley JJ, Endsley MA, Fennelly K, Franco-Paredes C, Hagge DA, Hall-Stoodley L, Hayes D, Hirschfeld K, Hofman CA, Honda JR, Hull NM, Kramnik I, Lacourciere K, Lahiri R, Lamont EA, Larsen MH, Lemaire T, Lesellier S, Lee NR, Lowry CA, Mahfooz NS, McMichael TM, Merling MR, Miller MA, Nagajyothi JF, Nelson E, Nuermberger EL, Pena MT, Perea C, Podell BK, Pyle CJ, Quinn FD, Rajaram MVS, Mejia OR, Rothoff M, Sago SA, Salvador LCM, Simonson AW, Spencer JS, Sreevatsan S, Subbian S, Sunstrum J, Tobin DM, Vijayan KKV, Wright CTO, Robinson RT. The Many Hosts of Mycobacteria 9 (MHM9): A conference report. Tuberculosis (Edinb). 2023 Sep; 142:102377. PMID: 37531864; PMCID: PMC10529179; DOI: 10.1016/j.tube.2023.102377;
     
  5. Krug S, Prasad P, Xiao S, Lun S, Ruiz-Bedoya CA, Klunk M, Ordonez AA, Jain SK, Srikrishna G, Kramnik I, Bishai WR. Adjunctive Integrated Stress Response Inhibition Accelerates Tuberculosis Clearance in Mice. mBio. 2023 Apr 25; 14(2):e0349622. PMID: 36853048; PMCID: PMC10128048; DOI: 10.1128/mbio.03496-22;
     
  6. Yabaji SM, Rukhlenko OS, Chatterjee S, Bhattacharya B, Wood E, Kasaikina M, Kholodenko B, Gimelbrant AA, Kramnik I. Cell state transition analysis identifies interventions that improve control of M. tuberculosis infection by susceptible macrophages. bioRxiv. 2023 Feb 10.View Related Profiles. PMID: 36798271; PMCID: PMC9934610; DOI: 10.1101/2023.02.09.527908;
     
  7. 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;
     
  8. 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;
     
  9. 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;
     
  10. 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;
     
Showing 10 of 66 results. Show More

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

Bar chart showing 66 publications over 28 distinct years, with a maximum of 6 publications in 2012

YearPublications
19902
19911
19933
19943
19971
19982
20001
20021
20041
20052
20062
20072
20084
20094
20101
20111
20126
20132
20141
20152
20162
20173
20192
20204
20215
20222
20235
20241
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620 Albany St
Boston MA 02118
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