The Nuñez laboratory is interested in signaling pathways regulating innate immunity, the pathogenesis of inflammatory disease and cancer. Specifically, the research focuses on mechanistic studies to understand the role of pattern recognition receptors (PRRs) including Nod-like receptors (NLRs) and Toll-like receptors (TLRs) in the host immune response against microbial pathogens and endogenous damage signals. Current studies focus on models of intestinal and skin inflammation driven by microbial pathogens, commensal bacteria and sterile organ injury. Several approaches that include analyses of genetically modified mutant mice and biochemical studies are used to determine mechanisms involved in the interaction between microbial/endogenous molecules and NLRs. Several NLR proteins including Nod2 and Nlrp3 are mutated in patients with inflammatory diseases (Crohn's disease and autoinflammatory syndromes). Studies to understand how NLR mutant proteins lead to disease are a major effort of the laboratory. Another line of investigation is the role of the microbiota in the colonization of enteric pathogens and pathogen-driven intestinal inflammation.
Kanneganti T-D, Özören N, Body-Malapel M, Amer A, Park J-P, 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 440:223-236 (2006).
Franchi L, Amer A, Body-Malapel M, Kanneganti TD, Ozoren N, Jagirdar R, Inohara N, Vandenabeele P, Bertin J, Coyle A, Grant EP, Núñez G. Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages. Nature Immunol. 7:576-582 (2006).
Kim YG, Park J-P, Shaw MH, Franchi L, Inohara N and Núñez G. Nod1 and Nod2 are Critical for Intracellular Bacterial Sensing and Host Defense after Exposure to Toll-like Receptors Ligands. Immunity, 28:246-57 (2008)
Kim YG, Kamada N., Shaw MH, Warner N., Chen GY, Franchi L., and Núñez G. Nod2 Orchestrates Immune Responses that Promote Intestinal Pathogen Eradication via CCL2-Dependent Recruitment of Inflammatory Monocytes. Immunity 34:769-780 (2011).
Kim YG, Park J-H, Reimer T, Baker DP, Kawai T, Kumar H, Shizuo Akira S,Wobus C, and Núñez G. Nod1 and Nod2 Signaling Augmented by Viral Infection through Type I Interferons Potentiate Lethality Induced by Secondary Bacterial Infection. Cell Host & Microbe 16;496-507 (2011).
Shaw MH, Kamada N, Kim YG, Núñez G. Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine. J Exp Med. 209:251-258 (2012). PMID: 22291094.
Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P, Suzuki S, Shaw M. H., Kim Y-G., and Núñez G. NLRC4-driven IL-1β Production Discriminates Between Pathogenic and Commensal Bacteria and Promotes Host Defense in the Intestine. Nature Immunol. 13:449-456 (2012).
Kamada N. Kim YG, Sham HP, Vallance BA, Puente JL, Martens EC, Núñez G. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336:1325, (2012).
Nakamura Y, Luigi Franchi L, Kambe N, Meng G, Strober Wand, Gabriel Núñez G. Critical Rolefor Mast Cells in IL-1β-Driven Skin Inflammation Induced by an Activating Nlrp3 mutation. Immunity, 37, 1–11 (2012).