Nunez_Gabriel biosketch

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					            Program Director/Principal Investigator (Last, First, Middle):

                                                        BIOGRAPHICAL SKETCH
            Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
                                       Follow this format for each person. DO NOT EXCEED FOUR PAGES.

 NAME                                                                          POSITION TITLE
 Nuñez, Gabriel                                                                Professor
 eRA COMMONS USER NAME (credential, e.g., agency login)
 EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
                  INSTITUTION AND LOCATION                                                        YEAR(s)                  FIELD OF STUDY
                                                                              (if applicable)
 University of Seville Medical School, Spain                                      MD            1971-1977          Medicine
 Southwestern Medical School, Dallas, TX                                     Fellow (Res)       1979-1982          Immunology
 Washington University, St. Louis, MO                                         Resident          1985-1989          Pathology
 Howard Hughes Medical Institute, St. Louis, MO                              Fellow (Res)       1987-1991          Molecular Biology
A. Positions and Honors

Positions and Employment
1979-82     Trainee in Immunology, University of Texas Southwestern Med School, Dallas, TX
1982-84     Instructor, Dept of Internal Medicine, University of Texas Southwestern Med School, Dallas, TX
1985-89     House Officer, Department of Pathology, Washington University School of Medicine,
            St. Louis, MO
1987-91     Trainee in Molecular Biology, Howard Hughes Med. Inst., Washington Univ. School of Medicine,
            St. Louis, MO
1991-96     Assistant Professor, Department of Pathology, University of Michigan Medical School,
            Ann Arbor, MI
1996-01     Associate Professor, Department of Pathology, University of Michigan Medical School,
            Ann Arbor, MI
2001-       Paul de Kruif Endowed Professor, Department of Pathology, University of Michigan Medical
            School, Ann Arbor, MI
2007-       Co-Director, Immunology and Host Response Program, University of Michigan Comprehensive
            Cancer Center, Ann Arbor, MI
1991-       390 Invited Seminars and Lectures including 9 Keynote or Honorary Lectures
1994-1999 Research Career Development Award, National Institutes of Health
1999-2004 Member, NIH Study Sections Pathology B, Pathology C and Cancer Biology and
2001        Dean’s Achievement Award in Basic Science, University of Michigan Med School
2008        Distinguished Faculty Lectureship Award, University of Michigan Med School
2007-       Section Editor, Journal of Immunology

B. Selected peer-reviewed publications (in chronological order, out of 235).
1. Merino, R., Ding, L., Veis, D., Korsmeyer, S.J., Nuñez, G.: Developmental regulation of the Bcl-2
    protein and susceptibility to cell death in B lymphocytes. EMBO J. 13:683-691 (1994).
2. Grillot, D.A.M., Merino, R., Pena. J.C., Fanslow, W.C., Finkelman, F.D., Thompson, C.B., Nuñez, G.:
    Bcl-xL exhibits regulated expression during B cell development and activation,and modulates
    lymphocyte survival in transgenic mice. J. Exp. Med. 183:1852-1862 (1996).
3. Wu, D., Wallen, H., Nuñez, G.: Interaction and regulation of subcellular localization of CED-4 by
    CED-9. Science. 275:1126-1128 (1997).
4. Inohara, N., Ding, D., Chen, S., Nuñez, G.: harakiri, a novel regulator of cell death, encodes a
    protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and
    Bcl-XL. EMBO J. 16:1686-1694 (1997).
                                                          PI Name
          Program Director/Principal Investigator (Last, First, Middle):
5.    Wu, D., Wallen, H.D., Inohara, N., Nuñez, G.: Interaction and regulation of the C. Elegans death
      protease CED-3 by CED-4 and CED-9. J. Biol .Chem. 272:21449-21454 (1997).
6.    del Peso, L., Gonzalez-Garcia, M., Page, C., Herrera, R., Nuñez, G.: Interleukin-3-Induced
      Phosphorylation of BAD through the Protein Kinase Akt. Science. 278:687-689 (1997).
7.    Koseki, T., Inohara, N., Chen, S., Nuñez, G.: ARC, an inhibitor of apoptosis expressed in skeletal
      muscle and heart that interacts selectively with caspases. Proc. Natl. Acad. Sci. USA. 95(9):5156-
      5160 (1998).
8.    Inohara, N., Koseki, T., Chen, S., Wu, X., Nuñez, G.: CIDE, a novel family of cell death activators
      with homology to the 45 kDa subunit of the DNA fragmentation factor. EMBO J. 17(9):2526-2533
9.    Inohara, N., Koseki, N., del Peso, L., Hu, Y., Yee, C., Chen, S., Carrio, R., Merino, J., Liu, D., Ni, J.,
      Nuñez, G. Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor B. J Biol Chem.
      274(21):14560-14567 (1999).
10.   Hu, Y., Benedict, M.A., Ding, L., Nuñez, G. Role of cytochrome c and dATP/ATP hydrolysis in Apaf-
      1-mediated caspase-9 activation and apoptosis. EMBO J. 18(13):3586-3595 (1999).
11.   Inohara, N., Koseki, T., Lin, J., del Peso, L., Lucas, P.C., Chen, F.F., Ogura, Y., Nuñez, G.: An
      induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways. J
      Biol Chem. 275(36):27823-31 (2000).
12.   Inohara, N., Ogura, Y., Chen, F.F., Muto, A., Nuñez, G.: Human Nod1 Confers Responsiveness to
      Bacterial Lipopolysaccharides. J Biol Chem. 276:2551-2554 (2001).
13.   Ogura, Y., Inohara, N., Benito, A., Chen, F.F., Yamaoka, S., Nuñez, G.: Nod2, a Nod1/Apaf-1 family
      member that is restricted to monocytes and activates NFkappaB. J Biol Chem. 276:4812-4818
14.   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.
15.   Kobayashi, K., Inohara, N., Hernandez, L.D., Galan, J.E., Nuñez, G., Janeway, C., Medzhitov, R.,
      Flavell, R.A. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive
      immune systems. Nature 416:194-199 (2002).
16.   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).
17.   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).
18.   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)
19.   Dowds TA, Masumoto J, Zhu L, Inohara N, Nuñez G . Cryopyrin induced IL-1 secretion in monocytic
      cells: Enhanced activity of disease-associated mutants and requirement for ASC. J Biol Chem
      279:21924-21928 (2004).
20.   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).
21.   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
22.   Özören N, Masumoto J, Franchi L, Kanneganti T-D, Body-Malapel M, Ertürk I*, Jagirdar R, Zhu L,
      Inohara N, Bertin J, Coyle A, Grant EP, and Núñez G. Distinct Roles of TLR2 and the Adaptor ASC in
      IL-1b/IL-18 Secretion in response to Listeria monocytogenes. J. Immunol 176:4337-4342 (2006).

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                                                      PI Name
          Program Director/Principal Investigator (Last, First, Middle):
23. 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

24. Amer A, Franchi L, Kanneganti TD, Body-Malapel M, Ozoren N, Brady G, Meshinchi S, Jagirdar R,
    Gewirtz A, Akira S, Núñez G. Regulation of Legionella phagosome maturation and infection through
    flagellin and host IPAF. J. Biol. Chem. 281:35217-35223 (2006).
25. Kanneganti TD, Body-Malapel M, Amer A, Park J,H., Whitfield J, Taraporewals Z, Miller, D Patton J.T.,
    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. 281:36560-36568 (2006).
26. 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).
27. 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).
28. 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).
29. 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).
30. Park JH, Kim YY, Shaw M, Kanneganti TD, Fujimoto Y, Fukase K, Inohara N, Núñez G. Nod1/RICK and
    TLR Signaling Regulate Chemokine and Antimicrobial Innate Immune Responses in Mesothelial Cells. J
    Immunol. 179: 514-521 (2007).
31. 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).
32. Franchi L, Stoolman J, Kanneganti TD, Verma A, Ramphal R, Núñez G. Critical role for Ipaf in
    Pseudomonas aeruginosa-induced caspase-1 activation. Eur J Immunol. 11:3030-3039 (2007).
33. Kanneganti TD, Lamkanfi M, Núñez G. Intracellular NOD-like receptors in host defense and disease.
    Immunity 4:549-559 (2007).
34. Hasegawa M, Fujimoto Y, Lucas PC, Nakano H, Fukase K, Núñez G, Inohara N. A critical role of
    RICK/RIP2 polyubiquitination in Nod-induced MF-B activation. EMBO J., 27:373-383 (2008). Pmcid:
35. 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).
36. Marina-García N., Franchi L., Kim Y-G., Miller D., McDonald C., Boons G-H., and Núñez G. Pannexin-
    1-Mediated Intracellular Delivery of Muramyl Dipeptide Induces Caspase-1 Activation via
    Cryopyrin/NLRP3 Independently of Nod2. J.Immunol, 6:4050-4057 (2008). (Published March 08)

C. Research Support


R01 DK067628 (Nuñez)                                                                     08/01/04 -07/30/09
Peptidoglycan signaling in Crohn’s disease
The major goal of this project is to determine the response of Crohn’s disease patients to peptidoglycan
products, activation of NOD2 protein complex and analysis of NOD2-binding proteins.

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          Program Director/Principal Investigator (Last, First, Middle):    PI Name
R01 AI0647748 (Nuñez)                                                                    05/15/05-04/30/10
Role of Ipaf in Inflammation and Host Defense
The major goals of this project are to characterize the Ipaf protein complex and characterize Ipaf mutant mice

R01 Al063331 (Nuñez)                                                                      05/01/05-01/31/10
Cryopyrin Signaling in Inflammation and Innate Immunity
The major goals of this project are to understand the activation of Cryopyrin by bacterial ligands and to
characterize, mutant mice deficient in cryopyrin

R01 1 AR051790 (Nuñez)                                                                02/01/06-07/30/11
Role of ASC Signaling Pathway in Inflammatory Disease
The major goals of this project are to generate mouse model of autoinflammatory disease, and study the role
of ASC in Innate Immunity and arthritis mouse models.

2R01 DK61707 (Nuñez)                                                                     08/01/07-07/31/12
Nod2: A Susceptibility Gene for Crohn’s Disease
The major goals of this project are to characterize the function of Nod2 in vivo using mouse models.

R01 1CA084064 (Nuñez)                                                                       07/01/00-06/31/05
Ciper: a novel NF-kappaB-activating gene involved in Cancer
The major goals are: (1) Further characterize the biological activities of Ciper (2) characterize the pathway of
NF-kappa activation induced by Ciper (3) study the expression of Ciper in normal and cancer cells (4) identify
cellular targets of Ciper and (5) generate mutant mice deficient in Ciper

R01 2-CA64556 (Nuñez)                                                                  06/01/99-05/31/04
Genetic Regulation of Apoptotic Cell Death
The major goals are to: 1) determine the biochemical mechanism by which Apaf-1 promotes the activation of
caspase-9; 2) determine the mechanism by which Bcl-xL inhibits activation of caspase-9 through Apaf-1; 3)
further characterize the interaction between Bcl-xL and Apaf-1; 4) determine the mechanism by which pro-
apoptotic Bcl-2 family members antagonize Bcl-xL through Apaf-1; and 5) determine if caspase-9 is required for
the protection against apoptosis afforded by Bcl-xL.

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