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Gabriel Nunez

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Primary Appointment: Pathology Department
Other PIBS Depts.: Molecular and Cellular Pathology



 DESCRIPTION OF RESEARCH
  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 proteins of the Nod-like receptor (NLR) and Toll-like receptor (TLR) families in the host immune response against microbial pathogens and endogenous danger signals. Several approaches that include analyses of genetically modified mutant mice, cell biology and biochemical studies are used to determine molecular mechanisms involved in the interaction between microbial/endogenous molecules and innate immune receptors. Several NLR proteins including Nod2 and Nlrp3/Nalp3 are mutated in patients with inflammatory diseases (Crohn's disease and autoinflammatory syndromes). Furthermore genetic variationin NLRs affect the susceptibility to asthma and sarcoidosis. Studies to understand how the NLR mutant proteins lead to disease are a major effort of the laboratory. Signaling pathways involved in inflammation and innate immunity are also known to play a role in cancer development particularly in the gastrointestinal tract. Understanding the mechanisms by which these pro-inflammatory pathways affect cancer initiation and/or progression in the intestinal tract is another interest of the laboratory.

Representative Publications:

1. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nuñez G* , Flavell RA* (* joint senior authors). Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 307:731-4 (2005).

2. 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).

3. 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).2006

4. Kanneganti TD, Lamkanfi M, Kim YG, Chen G, Park JH, Franchi L, Vandeenabeele P, Núñez G. Pannexin-1-Mediated Recognition of Bacterial Molecules Activates the Cryopyrin Inflammasome Independent of Toll-like Receptors Signaling. Immunity 26:433-443 (2007).
5. Lamkanfi M, Amer A, Kanneganti TD, Munoz-Planillo R, Chen G, Vandenabeele P, Fortier A, Gros P, Núñez G. The Nod-Like Receptor Family Member Naip5/Bircle Restricts Legionella pneumophila Growth Independently of Caspase-1 Activation. J Immunol 178:8022-8027 (2007).
6. Franchi L, Kanneganti TD, Dubyak GR, Núñez G. Differential Requirement of P2X7 Receptor and Intracellular K+ for Caspase-1 Activation Induced by Intracellular and Extracellular Bacteria. J Biol Chem. 282:18810-18818 (2007).
7. Park J.-H., Kim Y.-G., McDonald C., Kanneganti T.-D., Hasegawa M., Body-Malapel M., Inohara I., and Núñez G.. RICK/RIP2 Mediates Innate Immune Responses Induced Through Nod1 and Nod2 but not Toll-like Receptors. J. Immunology 178:2380-2386 (2007).
8. Suzuki T, Franchi L, Toma C, Ashida H, Ogawa M, Yoshikawa Y, Mimuro H, Inohara N, Sasakawa C, Núñez G. Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages. PLoS Pathog. 8:111 (2007).
9. Kanneganti TD, Lamkanfi M, Núñez G. Intracellular NOD-like receptors in host defense and disease. Immunity 4:549-559 (2007).
10. 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)