Skip to main content
Thirumala-Devi Kanneganti, PhD
Thirumala-Devi Kanneganti, PhD

Thirumala-Devi Kanneganti, PhD

Member, St. Jude Faculty

  • Vice-Chair, Immunology Department
  • Rose Marie Thomas Endowed Chair

Departments

Education

PhD

Honors & Awards

  • 2020 R35 Outstanding Investigator Award, National Cancer Institute
  • 2019  The most highly cited researchers in the world (Clarivates/Web of Science)
  • 2019  Jurgen Manchot Research Professorship
  • 2018  Seymour & Vivian Milstein Award for Excellence in Interferon and Cytokine Research
  • 2018  The most highly cited researchers in the world (Clarivates/Web of Science)
  • 2017  MERIT Award, National Institute of Allergy and Infectious Diseases
  • 2017  The most highly cited researchers in the world (Clarivates/Web of Science)
  • 2017  Eli Lilly and Company-Elanco Research Award, American Society for Microbiology
  • 2017  Outstanding macrophage researcher Dolph O. Adams award, Society for Leukocyte Biology
  • 2017  Elected Foreign Fellow of the Telangana Academy of Sciences
  • 2017  Elected to the Society of Mucosal Immunology Board of Councilors
  • 2016  Chair, National Institute of Health, Innate Immunity and Inflammation Study Section
  • 2016  MERIT Award, National Institute of Health
  • 2015  Vince Kidd Memorial Mentor of the Year Award
  • 2015  Elected Chair, American Society for Microbiology, Immunology
  • 2015  Investigator Award from the American Association of Immunology-BD Biosciences
  • 2002  The Jawaharlal Nehru Award for Outstanding Post-Graduate Research
  • 2002  Outstanding Young Scientist Award

Research Interests

  • Innate immunity
  • Inflammasomes and cell death
  • Inflammatory and infectious diseases
  • Nucleic acid sensing and signaling pathways

My laboratory is interested in understanding how the innate immune system recognizes and responds to pathogens and how genetic mutations in innate immunity affect the development of infectious, inflammatory, and autoimmune diseases in humans. 

As a founding member of the inflammasome field, my lab continues to make critical contributions to this research area. We provided the first genetic evidence for the role of NLRP3 in inflammasome activation and established its importance in infection, inflammation, and cancer. Our studies identified ZBP1 and TAK1 as master regulators of inflammasome activation and the cell death pathways pyroptosis, apoptosis, and necroptosis, leading us to pioneer the concept of PANoptosis and describe its implications in health and disease. PANoptosis is defined as a unique inflammatory programmed cell death regulated by the PANoptosome, which provides a molecular scaffold that allows for interactions and activation of the machinery required for inflammasome/pyroptosis (NLRP3, ASC, caspase-1), apoptosis (caspase-8), and necroptosis (RIPK3/RIPK1). Additionally, we have identified the activation mechanisms of other inflammasomes; characterized other key innate sensing pathways; and described distinct, novel roles for IL-1α, IL-1β, and IL-33 in disease. Overall, with more than 260 manuscripts, all focused on innate immunity, inflammasomes, and cell death, our studies have contributed to both the inception and the maturation of the inflammasome field as a major research area in immunology and as a site for therapeutic innovation.

Selected Publications

Zheng M, Karki R, Vogel P, Kanneganti TD. Caspase-6 is a key regulator of innate immunity, inflammasome activation, and host defense. Cell 181(3):674-687, 2020.

Christgen S, Zheng M, Kesavardhana S, Karki R, Malireddi RKS, Banoth B, Place DE, Briard B, Sharma BR, Tuladhar S, Samir P, Burton A, Kanneganti TD. Identification of the PANoptosome: A molecular platform triggering pyroptosis, apoptosis, and necroptosis (PANoptosis). Front Cell Infect Microbiol 10:237, 2020.

Zheng M, Williams EP, Malireddi RKS, Karki R, Banoth B, Burton A, Webby R, Chnnappanavar R, Jonsson CB, Kanneganti TD. Impaired NLRP3 inflammasome activation/pyroptosis leads to robust inflammatory cell death via caspase-8/RIPK3 during coronavirus infection J Biol Chem [Epub ahead of print], 2020.

Karki R, Sharma BR, Lee E, Banoth B, Malireddi RKS, Samir P, Tuladhar S, Mummareddy H, Burton AR, Vogel P, Kanneganti TD. Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer. JCI Insight 5(12):136720, 2020.

Malireddi RKS, Gurung P, Kesavardhana S, Samir P, Burton A, Mummareddy H, Vogel P, Pelletier S, Burgula S, Kanneganti TD. Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity-independent pyroptosis, apoptosis, necroptosis, and inflammatory disease. J Exp Med 217(3):pii:e20191644, 2020.

Samir P, Kesavardhana S, Patmore DM, Gingras S, Malireddi RKS, Karki R, Guy CS, Briard B, Place DE, Bhattacharya A, Sharma BR, Nourse A, King SV, Pitre A, Burton AR, Pelletier S, Gilbertson RJ, Kanneganti TD. DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome. Nature 573(7775):590–594, 2019.

Karki R, Kanneganti TD. Diverging inflammasome signals in tumorigenesis and potential targeting. Nat Rev Cancer 19(4):197–214, 2019.

Briard B, Karki R, Mallireddi RKS, Bhattacharya A, Place DE, Mavuluri J, Peters JL, Vogel P, Yamamoto M, Kanneganti TD. Fungal ligands released by innate immune effectors promote inflammasome activation during Aspergillus fumigatus infection. Nat Micobiol 4(2):316–327, 2019.

Karki R, Lee E, Place D, Samir P, Mavuluri J, Sharma BR, Balakrishnan A, Mallireddi RKS, Geiger R, Zhu Q, Neale G, Kanneganti TD. IRF8 regulates transcription of Naips for NLRC4 inflammasome activation. Cell 173(4):920–933, 2018.

Malireddi RKS, Gurung P, Mavuluri J, Dasari TK, Klco JM, Chi H, Kanneganti TD. TAK1 restricts spontaneous NLRP3 activation and cell death to control myeloid proliferation. J Exp Med 215(4):1023–1034, 2018.

Kanneganti TD. Inflammatory Bowel Disease and the NLRP3 Inflammasome. New Engl J Med Aug 17;377(7):694-696, 2017.

Gurung P, Fan G, Lukens JR, Vogel P, Tonks N and Kanneganti TD. Tyrosine kinase SYK licenses MyD88 adaptor protein to instigate IL-1α-mediated inflammatory disease. Immunity 46(4):635-648, 2017. 

Kesavardhana S, Kuriakose T, Guy CS, Samir P, Malireddi R KS, Mishra A, Kanneganti TD. ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death. Journal of Experimental  Medicine 214(8):2217-2229, 2017.

Sharma D, Malik A, Guy C, Karki R, Vogel P, and Kanneganti TD. Pyrin Inflammasome Regulates Tight Junction Integrity to Restrict Colitis and Tumorigenesis. Gastroenterology Dec 1. pii: S0016-5085(17)36665-9, 2017.

Karki R, Man, SM, Malireddi RK, Kesavardhana S, Zhu Q, Burton AR, Sharma BR, Pelletier S, Vogel P, Rosenstiel P, Kanneganti TD. NLRC3 is a tumour suppressor and regulatory sensor of mTOR pathways. Nature 540(7634):583-587, 2016.

Malik A, Sharma D, Zhu Q, Karki R, Guy CS, Vogel P, Kanneganti TD. IL-33 regulates the IgA-microbiota axis to restrain IL-1α dependent colitis and tumorigenesis. Journal of Clinical Investigation 126(12):4469-4481, 2016.

Man SM, Karki R, Sasai M, Place DE, Kesavardhana S, Temirov J, Frase S, Zhu Q, Malireddi RK, Kuriakose T, Peters JL, Neale G, Brown SA, Yamamoto M, Kanneganti TD. IRGB10 liberates bacterial ligands for sensing by the AIM2 and caspase-11-NLRP3 inflammasomes. Cell  167(2):382-396.e17, 2016.

Kuriakose T, Man SM, Malireddi RK, Karki R, Kesavardhana S, Place DE, Neale G, Vogel P, Kanneganti TD. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Science Immunology 1(2):aag2045, 2016.

Gurung P, Burton A, Kanneganti TD. NLRP3 inflammasome plays a redundant role with caspase-8 to promote IL-1β-mediated osteomyelitis. Proc Natl Acad Sci USA 113(16):4452–4457, 2016.

Man SM, Kanneganti TD. Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nature Reviews Immunology Jan;16(1):7-21, 2016.

Man SM, Zhu Q, Zhu L, Liu Z, Karki R, Malik A, Sharma D, Li L, Malireddi RK, Gurung P, Neale G, Olsen SR, Carter RA, McGoldrick DJ, Wu G, Finkelstein D, Vogel P, Gilbertson RJ, Kanneganti TD. Critical Role for the DNA Sensor AIM2 in Stem Cell Proliferation and Cancer. Cell 2;162(1):45-58, 2015.

Man SM, Karki R, Malireddi RK, Neale G, Vogel P, Yamamoto M, Lamkanfi M, Kanneganti TD. The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection. Nature Immunology 16(5):467-75, 2015.

Lukens JR, Gurung P, Shaw PJ, Barr MJ, Zaki MH, Brown SA, Vogel P, Chi H, Kanneganti TD. The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells. Immunity 21;42(4):654-64, 2015.

Karki R, Man SM, Malireddi RK, Gurung P, Vogel P, Lamkanfi M, Kanneganti TD. Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection. Cell Host Microbe 11;17(3):357-68, 2015.

Lukens JR, Gurung P, Vogel P, Johnson GR, Carter RA, McGoldrick DJ, Bandi SR, Calabrese CR, Walle LV, Lamkanfi M, Kanneganti TD. Dietary modulation of the microbiome affects autoinflammatory disease. Nature 512(7512):69-73, 2014.

Gurung P, Anand PK, Malireddi RK, Vande Walle L, Van Opdenbosch N, Dillon CP, Weinlich R, Green DR, Lamkanfi M, Kanneganti TD. FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. J Immunol 192(4):1835–1846, 2014.

Lukens JR, Gross JM, Calabrese C, Iwakura Y, Lamkanfi M, Vogel P, Kanneganti TD. Critical role for inflammasome-independent IL-1beta production in osteomyelitis. Proc Natl Acad Sci USA 111(3):1066-1071, 2014.

Lukens JR, Vogel P, Johnson GR, Kelliher MA, Iwakura Y, Lamkanfi M, Kanneganti TD. RIP1-driven autoinflammation targets IL-1 alpha independently of inflammasomes and RIP3. Nature 498(7453):224-227, 2014.

Lupfer C, Thomas PG, Anand PK, Vogel P, Milasta S, Martinez J, Huang G, Green M, Kundu M, Chi H, Xavier RJ, Green DR, Lamkanfi M, Dinarello CA, Doherty PC, Kanneganti TD. Receptor interacting protein kinase 2- mediated mitophagy regulates inflammasome activation during virus infection. Nature Immunology 14(5):480-488, 2013.

Anand PK, Malireddi RK, Lukens JR, Vogel P, Bertin J, Lamkanfi M, Kanneganti TD. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488(7411):389-393, 2012.

View full publication list 

Show More

Kanneganti TD, Dixit VD. Immunological complications of obesity. Nature Immunology 13(8):707-712, 2012.

Zaki MH, Vogel P, Malireddi RK, Body-Malapel M, Anand PK, Bertin J, Green DR, Lamkanfi M, Kanneganti TD. The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis. Cancer Cell 20(5):649- 60, 2011.

Shaw PJ, Barr MJ, Lukens JR, McGargill MA, Chi H, Mak TW, Kanneganti TD. Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity. Immunity 34(1):75-84, 2011.

Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL, Perera D, Neale GA, Hooiveld GJ, Hijmans A, Vroegrijk I, van den Berg S, Romijn J, Rensen PCN, Joosten LAB, Netea MG, Kanneganti TD. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci USA 108(37):15324-15329, 2011.

Malireddi RK, Ippagunta S, Lamkanfi M, Kanneganti TD. Cutting edge: proteolytic inactivation of poly(ADP-ribose) polymerase 1 by the Nlpr3 and Nlrc4 inflammasomes. J Immunol 185(6):3127–3130, 2010.

Kanneganti TD. Central roles of NLRs and inflammasomes in viral infection. Nature Reviews Immunology 10(10):688-98, 2010.

Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti TD. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32(3):379–391, 2010.

Thomas PG, Dash P, Aldridge JR Jr, Ellebedy AH, Reynolds C, Funk AJ, Martin WJ, Lamkanfi M, Webby RJ, Boyd KL, Doherty PC, Kanneganti TD. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity 30(4):566–575, 2009.

Lamkanfi M, Kanneganti TD, Van Damme P, Vanden Berghe T, Vanoverberghe I, Vandekerckhove J, Vandenabeele P, Gevaer, K, Nunez G. Targeted peptidecentric proteomics reveals caspase-7 as a substrate of the caspase-1 inflammasomes. Mol Cell Proteomics 7(12):2350-2363, 2008.

Kanneganti TD, Body-Malapel M, Amer A, Park JH, Whitfield J, Franchi L, Taraporewala ZF, Miller D, Patton JT, Inohara N, Nunez G. Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J Biol Chem 281(48):36560–36568, 2006.

Kanneganti TD, Ozoren N, Body-Malapel M, Amer A, Park JH, Franchi L, Whitfield J, Barchet W, Colonna M, Vandenabeele P, Bertin J, Coyle A, Grant EP, Akira S, Nunez G. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440(7081):233–236, 2006.

Last update: August 2020