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

Thirumala-Devi Kanneganti, PhD

Member, St. Jude Faculty




Research Interests

Molecular Mechanisms of Innate Immunity and Inflammation

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. Our initial studies have unraveled key roles for Nod-like Receptors and their adaptor proteins in response to pathogens and endogenous danger signals (Nature 440(7081):233-36; Nature Immunology 7(6):576-82, 2011; Cancer Cell 20(5):649-60, 2011; Nature 488(7411):389-93, 2012; Nature Immunology 14(5):480-488, 2013). Although extensive advances have been made in recent years to define the inflammatory processes that are required for pathogen clearance, very little is known about the regulation of inflammation in sterile settings. Importantly, over the past decade non-communicable chronic diseases that are potentiated by sterile inflammation have replaced infectious diseases as the major threat to global human health. Thus, improved understanding of the sterile inflammatory process has emerged as one of the most important areas of biomedical investigation of our time. Ongoing studies from our lab are investigating the sophisticated system governing the activation of signaling cascades and the mechanisms involved in the regulation of inflammation in autoinflammatory diseases (Nature 498(7453):224-7, 2013; Nature 512(7512):69-73, 2014) and cancer (Cell 162(1):45-58).

Selected Publications

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.

Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nature Medicine 21(3):263-9, 2015.

Martinez J, Malireddi RK, Lu Q, Cunha LD, Pelletier S, Gingras S, Orchard R, Guan JL, Tan H, Peng J, Kanneganti TD, Virgin HW, Green DR. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nature Cell Biology 17(7):893-906, 2015.

Gurung P, Man SM, Kanneganti TD. A20 is a regulator of necroptosis. Nature Immunology 16(6):596-7, 2015.

Paugh SW, Bonten EJ, Savic D, Ramsey LB, Thierfelder WE, Gurung P, Malireddi RK, Actis M, Mayasundari A, Min J, Coss DR, Laudermilk LT, Panetta JC, McCorkle JR, Fan Y, Crews KR, Stocco G, Wilkinson MR, Ferreira AM, Cheng C, Yang W, Karol SE, Fernandez CA, Diouf B, Smith C, Hicks JK, Zanut A, Giordanengo A, Crona D, Bianchi JJ, Holmfeldt L, Mullighan CG, den Boer ML, Pieters R, Jeha S, Dunwell TL, Latif F, Bhojwani D, Carroll WL, Pui CH, Myers RM, Guy RK, Kanneganti TD, Relling MV, Evans WE. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells. Nature Genetics 47(6):607-14, 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.

Kanneganti TD, Kundu M, Green DR. Innate immune recognition of mtDNA--an undercover signal? Cell Metabolism 2;21(6):793-4, 2015.

Walsh JT, Hendrix S, Boato F, Smirnov I, Zheng J, Lukens JR, Gadani S, Hechler D, Gölz G, Rosenberger K, Kammertöns T, Vogt J, Vogelaar C, Siffrin V, Radjavi A, Fernandez-Castaneda A, Gaultier A, Gold R, Kanneganti TD, Nitsch R, Zipp F, Kipnis J. MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4.  Journal of Clinical Investigation 125(6):2547, 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.

Li B, Gurung P, Malireddi RK, Vogel P, Kanneganti TD, Geiger TL. IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity during T-cell-mediated colitis. Nature Communication 21;6:6131, 2015.

Matusiak M, Van Opdenbosch N, Vande Walle L, Sirard JC, Kanneganti TD, Lamkanfi M. Flagellin-induced NLRC4 phosphorylation primes the inflammasome for activation by NAIP5. Proc Natl Acad Sci U S A 3;112(5):1541-6, 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. 

Vande Walle L, Van Opdenbosch N, Jacques P, Fossoul A, Verheugen E, Vogel P, Beyaert R, Elewaut D, Kanneganti TD, van Loo G, Lamkanfi M. Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis. Nature 512(7512): 69-73, 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.

Dillon CP, Weinlich R, Rodriguez DA, Cripps JG, Quarato G, Gurung P, Verbist KC, Brewer TL, Llambi F, Gong YN, Janke LJ, Kelliher MA, Kanneganti TD, Green DR. RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3. Cell 157(5):1189-1202, 2014. 

Demon D, Kuchmiy A, Fossoul A, Zhu Q, Kanneganti TD*, Lamkanfi M. Caspase-11 is expressed in the colonic mucosa and protects against dextran sodium sulphate-induced colitis. Mucosal Immunology , 2014. doi: 10.1038/mi.2014.36.

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.

Van Opdenbosch N, Gurung P, Vande Walle L, Kanneganti TD*, Lamkanfi M*. Activation of the NLRP1b inflammasome independently of ASC- mediated caspase-1 autoproteolysis and speck formation. Nature Communications 5:3209, 2014.

Zaki MH, Man SM, Vogel P, Lamkanfi M, Kanneganti TD. Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection. Proc Natl Acad Sci USA 111(1):385-390, 2014.

Freigang S, Ampenberger F, Weiss A, Kanneganti TD, Iwakura Y, Hersberger M, Kopf M. Fatty acid-induced mitochondrial uncoupling elicits inflammasome- independent IL-1 alpha and sterile vascular inflammation in atherosclerosis. Nature Immunology 14(10):1045-1053, 2013.

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.

Kanneganti TD, Lamkanfi M. K+ drops tilt the NLRP3 inflammasome. Immunity 38(6):1085-8, 2013. 

Show More

Zaki MH, Man SM, Vogel P, Lamkanfi M, Kanneganti TD. Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection. Proc Natl Acad Sci USA 111(1):385-390, 2013.

Huang G, Wang Y, Vogel P, Kanneganti TD, Otsu K, Chi H. Signaling via the kinase p38 programs dendritic cells to drive TY17 differentiation and autoimmune inflammation. Nature Immunology 13(2):152-161, 2012.

Ippagunta SK, Malireddi RK, Shaw PJ, Neale GA, Vande Walle L, Fukui Y, Green DR, Lamkanfi M, Kanneganti TD. Addendum: Defective Dock2 expression in a subset of ASC-deficient mouse lines. Nature Immunology 13(7):701-702, 2012.

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. 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.

Ippagunta SK, Malireddi RK, Shaw PJ, Neale GA, Walle LV, Green DR, Fukui Y, Lamkanfi M, Kanneganti TD. The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization. Nature Immunology 12(10):1010-1016, 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.

Huang G, Wang Y, Shi LZ, Kanneganti TD, Chi H. Signaling by the phosphatase MKP-1 in dendritic cells imprints distinct effector and regulatory T cell fates. Immunity 35(1):45-58, 2011.

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

Hasan Z, Ippagunta S, Boyd KL, Kastan MB, Lamkanfi M, Kanneganti TD. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32(3):379-91, 2010.

Thomas PG, Dash P, Aldridge JR Jr, Ellebedy AH, Reynolds C, Funk A J, 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):566-75, 2009. 

Last update: September 2015