Gabriel Nuñez, M.D.
Paul H. de Kruif Endowed Professor,
Department of Pathology

bclx@umich.edu

The Nuñez's laboratory is interested in signaling pathways regulating apoptosis and innate immunity and their role in 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 bacterial pathogens. Several approaches that include analyses of genetically modified mutant mice, cell biology and biochemical studies are used to determine molecular mechanisms involved in microbial-host interactions. Several NLR proteins including Nod2 and Cryopyrin are mutated in patients with inflammatory diseases (Crohn's disease and autoinflammatory syndromes) and studies to understand how the 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 is another interest of the laboratory.

Representative Publications

Ogura, Y., Bonen, D.K., Inohara, N., Nicolae, D.L., Chen, F.F., Ramos, R., Britton, H., Moran, T, Karaliuskas, R., Duerr, R.H., Achkar, J-P., Brant, S.R., Bayless, T.M., Kirschner, B.S., Hanauer, S.B., Nuñez, G .* and Cho, J.H.* (*joint senior authors). A frameshift mutation in Nod2 associated with susceptibility to Crohn's disease. Nature 411:603-606, 2001.

Inohara, N., Ogura, Y., Fontalba, A., Gutierrez, O., Pons, F., Crespo, J., Fukase, K., Inamura, S., Kusumoto, S., Hashimoto, M., Foster, S.J., Moran, A.P., Fernandez-Luna, J.L., Nuñez, G . Host recognition of bacterial muramyl dipeptide mediated through NOD2: implications for Crohn's disease. J Biol Chem 278:5509-55012 (2003)

Chamaillard M, Hashimoto M, Horie Y, Masumoto J, Qiu S, Saab L, Ogura Y, Kawasaki A, Fukase K, Kusumoto S, Valvano MA, Foster SJ, Mak TW, Nuñez G , Inohara N. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol, 4:702-707, 2003.

Tanabe T, Chamaillard M, Ogura Y, Zhu L, Qiu S, Masumoto J, Ghosh P, Moran A, Predergast MM, Tromp G, Williams CJ, Inohara N, Nuñez G . Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition. EMBO J . 7; 23:1587-1597 (2004).

Dowds TA, Masumoto J, Zhu L, Inohara N, Nuñez G . Cryopyrin induced IL-1beta secretion in monocytic cells: Enhanced activity of disease-associated mutants and requirement for ASC. J Biol Chem 279:21924-21928 (2004).

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

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. Nat Immunol . 7:576-582 (2006).