Thirumala-Devi Kanneganti, PhD
Thirumala-Devi Kanneganti, PhD

Thirumala-Devi Kanneganti, PhD

Member, St. Jude Faculty

  • Vice-Chair, Immunology Department
  • Director, Center of Excellence for Innate Immunity and Inflammation
  • Rose Marie Thomas Endowed Chair

Departments

Education

PhD

Honors & Awards

  • 2024 American Association of Immunology-Thermo Fisher Meritorious Career Award
  • 2023  Fellow in the American Association for the Advancement of Science (AAAS)
  • 2023  Rosalind Franklin Society Special Award in Science
  • 2023  The most highly cited researchers in the world (Clarivate Analytics/Web of Science) - with citations in the top 1% in Immunology over the past decade (top 0.1% of all researchers) - awarded 7 years running (2017–2023)
  • 2022  Outstanding Scientist Award, AAIS in Cancer Research
  • 2021  Fellow in the American Academy of Microbiology, American Society for Microbiology
  • 2020  R35 Outstanding Investigator Award, National Cancer Institute
  • 2019  Jurgen Manchot Research Professorship
  • 2018  Seymour & Vivian Milstein Award for Excellence in Interferon and Cytokine Research
  • 2017  MERIT Award, National Institute of Allergy and Infectious Diseases
  • 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 inflammatory cell death, PANoptosis
  • Inflammatory and infectious diseases and cancer
  • Cytokine signaling

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 and cancers 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, metabolic disease, and cancer. Our studies identified the critical cell death molecules caspase-8, ZBP1, RIPK1, TAK1, AIM2, NLRC5, and NLRP12 as master regulators of inflammasome activation and inflammatory cell death, leading us to pioneer the concept of PANoptosis and describe its implications in health and disease. PANoptosis is a prominent unique lytic, innate immune, inflammatory cell death pathway initiated by innate immune sensors and driven by caspases and RIPKs through multiprotein PANoptosome complexes. My laboratory has found that cytosolic innate immune sensors and regulators, such as ZBP1, AIM2, RIPK1, NLRC5, and NLRP12, promote the assembly of PANoptosomes to drive PANoptosis.

Additionally, we have identified the activation mechanisms of several inflammasomes, including NLRP3, NLRC4, Pyrin, and AIM2, in infection, inflammatory disease, and cancer; characterized other key innate sensing pathways; and elucidated regulatory mechanisms and novel roles for cytokines, including IL-1 family members, and the synergism between TNF and IFN-γ, which induces inflammatory cell death and the “cytokine storm.” Overall, with more than 340 publications, all focused on innate immunity, inflammation, and molecular mechanisms of 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 and pioneered the PANoptosis concept to identify new treatment strategies.

Kanneganti Research Lab

Contact Information

Thirumala-Devi Kanneganti, PhD Immunology MS 351, Room M5426 St. Jude Children's Research Hospital 262 Danny Thomas Place Memphis, TN 38105-3678

St. Jude Faculty List

Related Topics

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Selected Publications

NLRP3 inflammasome—inception and maturation of the inflammasome field

Briard B, Fontaine T, Samir P, Place DE, Muszkieta L, Malireddi RKS, Karki R, Christgen S, Bomme P, Vogel P, Beau R, Mellado E, Ibrahim-Granet O, Henrissat B, Kalathur RC, Robinson C, Latge JP, Kanneganti TD. Galactosaminogalactan activates the inflammasome to provide host protection. Nature 588(7839):688–692, 2020.

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

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.

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 Immunol 1(2):aag2045, 2016.

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

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.

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.

Kanneganti TD, Body-Malapel M, Amer A, Park JH, Whitfield J, Franchi L, Taraporewala ZF, Miller D, Patton JT, Inohara N, Núñez 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, Ozören 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, Núñez G. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440(7081):233-236, 2006

Cell death crosstalk and the discovery of ZBP1 and the PANoptosis pathway

Sundaram B, Pandian N, Kim HJ, Abdelaal HM, Mall R, Indari O, Sarkar R, Tweedell RE, Alonzo EQ, Klein J, Pruett-Miller SM, Vogel P, Kanneganti TD. NLRC5 senses NAD+ depletion to form a PANoptosome driving PANoptosis and inflammation. Cell. 2024. [Epub ahead of print].  

Sundaram B, Pandian N, Mall R, Wang Y, Sarkar R, Kim HJ, Malireddi RKS, Karki R, Janke LJ, Vogel P, Kanneganti TD. NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs. Cell 2783–2801, 2023. 

Karki R, Lee S, Mall R, Pandian N, Wang Y, Sharma BR, Malireddi RKS, Trifkovic S, Vogel P, Webby, R, Kanneganti TD. ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection. Science Immunol 7(74):eabo6294, 2022. 

Karki R, Sundaram B, Sharma BR, Lee S, Malireddi RKS, Nguyen LN, Christgen S, Zheng M, Wang Y, Samir P, Neale G, Vogel P, Kanneganti TD. ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. Cell Rep 37(3):109858, 2021.

Lee S, Karki R, Wang Y, Nguyen LN, Kalathur RC, Kanneganti TD. AIM2 forms a complex with Pyrin and ZBP1 to drive PANoptosis and host defence. Nature 597(7876):415–419, 2021.

Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, Zheng M, Sundaram B, Banoth B, Malireddi RKS, Schreiner P, Neale G, Vogel P, Webby R, Jonsson CB, Kanneganti TD. Synergism of TNF-a and IFN-g triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell 184(1):149–168.e17, 2021.

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.

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):e20191644, 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, 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.

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 Immunol 1(2):aag2045, 2016.

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

Lukens JR, Gurung P, Vogel P, Johnson GR, Carter RA, McGoldrick DJ, Bandi SR, Calabrese CR, Vande Walle L, Lamkanfi M, Kanneganti TD. Dietary modulation of the microbiome affects autoinflammatory disease. Nature 516(7530):246–249, 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.

Malireddi RK, Ippagunta S, Lamkanfi M, Kanneganti TD. Cutting edge: proteolytic inactivation of poly(ADP-ribose) polymerase 1 by the Nlrp3 and Nlrc4 inflammasomes. J Immunol 185(6):3127–3130, 2010.

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

Innate immunity, cell death, and cytokine pathways in diseases (infection, inflammation, cancer)

Wang Y, Karki R, Mall R, Sharma BR, Kalathur RC, Lee S, Kancharana B, So M, Combs KL, Kanneganti TD. Molecular mechanism of RIPK1 and caspase-8 in homeostatic type I interferon production and regulation. Cell Rep 41(1):111434, 2022.

Zheng M, Karki R, Williams EP, Yang D, Fitzpatrick E, Vogel P, Jonsson CB, Kanneganti TD. TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nature Immunol 22(7):829–838, 2021.

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

Karki R, Lee E, Place DE, Samir P, Mavuluri J, Sharma BR, Balakrishnan A, Malireddi RKS, Geiger R, Zhu Q, Neale G, Kanneganti TD. IRF8 regulates transcription of Naips for NLRC4 inflammasome activation. Cell 173(4):920–933.e13, 2018.

Malik A, Sharma D, Malireddi RKS, Guy CS, Chang TC, Olsen SR, Neale G, Vogel P, Kanneganti TD. SYK-CARD9 signaling axis promotes gut fungi-mediated inflammasome activation to restrict colitis and colon cancer. Immunity 49(3):515–530.e5, 2018.

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

Karki R, Man SM, Malireddi RKS, Kesavardhana S, Zhu Q, Burton AR, Sharma BR, Qi X, Pelletier S, Vogel P, Rosenstiel P, Kanneganti TD. NLRC3 is an inhibitory sensor of PI3K-mTOR pathways in cancer. Nature 540(7634):583–587, 2016.

Man SM, Karki R, Sasai M, Place DE, Kesavardhana S, Temirov J, Frase S, Zhu Q, Malireddi RKS, 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.

Man SM, Zhu Q, Zhu L, Liu Z, Karki R, Malik A, Sharma D, Li L, Malireddi RK, Gurung P, Neale G, Olsen SR, Cater 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 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 Immunol 16(5):467–475, 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 42(4):654–664, 2015.

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

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):649–660, 2011.

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Last update: July 2024

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