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Neil Warner, Ph.D.
e-mail address: neilwarn@umich.edu

Mentor: Gabriel Nunez, M.D.

Techniques Used:
Immunoprecipitation, western blots, siRNA knockdown, luciferase reporter assays, mass Spectrometry


Research Description:

I became interested in biology and genetics while pursuing my undergraduate degree in Molecular Biology and Biotechnology at McMaster University in Hamilton , Ontario , Canada . During my Ph.D. training at the University of Toronto, under the supervision of Dr. Tony Pawson (http://pawsonlab.mshri.on.ca), my research focused on understanding the role of modular protein domains in the regulation of protein kinase based signal transduction pathways. My interests in protein kinase signaling and the role of modular domains as building blocks to assemble multiprotein regulatory complexes brought me to the Dr. Gabriel Nunez's laboratory for my postdoctoral studies. Here I am interested in understanding the molecular mechanisms by which the intracellular Nod-like family of innate immune receptors (NLRs) regulate inflammation, cell death, and host defense. The modular domain architecture of this family is highly conserved across vertebrates and is commonly used to further subclassify NLR family members. One subclass of NLRs initiates a cascade of downstream kinases culminating in the regulation of critical transcriptional regulators such as the NF-kB family while another subclass plays an important role in the regulation of the inflammatory protease, Caspase-1. Clinically the deregulation of several members of the Nod-like family of receptors has been implicated in a variety of human inflammatory disorders.

My current research is focused on investigating both normal signal transduction events downstream of Nod-like receptors and their disruption in diseased states. In particular, I am undertaking both biochemical and genetics approaches to identify and characterize novel regulators of Nod2, a NLR family member known to be deregulated in a variety of inflammatory disorders including Crohn's disease and Blau Syndrome.


Publications:

Warner, N.*, Burberry, A.*, Franchi, F., Kim, Y.G., McDonald, C., Sartor, M.A., and Nuñez, G. (2013). A genome-wide siRNA screen reveals positive and negative regulators of the NOD2 and NF-κB signaling pathways. Science Signaling. 6(258):rs3.

Warner, N., and Nuñez, G. (2013). MyD88: a critical adaptor protein in innate immunity signal transduction. J. Immunol. 190(1):3.

Kim, Y.G., Shaw, M.H., Warner, N., Park, J.H., Ogura, Y., Chen, F., Nuñez, G. (2011). Crohn’s disease- associated Nod2 mutation limits production of proinflammatory cytokines to protect the host from Enterococcus faecalis induced lethality. J. Immunol. 187(6):2849.

Kim, Y.G., Kamada, N., Shaw, M.H., Warner, N., Chen, G.Y., Franchi, L., and Nuñez, G. (2011). The Nod2 Sensor Promotes Intestinal Pathogen Eradication via the Chemokine CCL2-Dependent Recruitment of Inflammatory Monocytes. Immunity. 34(5):769.

Shaw, M.H., Kamada, N., Warner, N., Kim, Y.G., Nuñez, G. (2011). The ever-expanding function of NOD2: Autophagy, Viral recognition, and T cell activation. Trends in Immunology. 32(2):73.

Shaw, M.H., Reimer, T., Sánchez-Valdepeñas, C.,
Warner, N., Kim, Y.G., Fresno, M., Nuñez, G. (2009) T cell intrinsic role of Nod2 in promoting type I immunity against Toxoplasma gondii. Nat. Immunology. 10:1267.

Franchi, L., Warner, N. , Viani, K., Nunez, G. (2009). Function of Nod-like receptors in microbial recognition and host defense. Immunological Reviews. 227(1):106.

Warner, N., Wybenga-Groot, L.E., Pawson, T. (2008). Analysis of EphA4 receptor tyrosine kinase substrate specificity using peptide-based arrays. TheFEBS Journal. 275(10):2561.

Fawcett, J.P., Georgiou, J., Ruston , J., Bladt, F., Sherman , A., Warner, N. , Saab, B.J., Scott, R., Roder, J.C., Pawson, T. (2007) Nck adaptor proteins control the organization of neuronal circuits important for walking. PNAS. 104(52):20973.

Pawson, T. and Warner, N. (2007). Oncogenic re-wiring of cellular signaling pathways. Oncogene. 26(9):1268.

Wiesner, S., Wybenga-Groot, L.E., Warner, N ., Li n, H., Pawson, T., Forman-Kay, J.D., Sicheri F. (2006). A change in conformational dynamics underlies the activation of Eph receptor tyrosine kinases. EMBO. 25(19):4686.

Kwan J.J., Warner N. , Maini J., Chan Tung K.W., Zakaria H., Pawson T.,Donaldson L.W. (2006). Saccharomyces cerevisiae Ste50 binds the MAPKKK Ste11 through a head-to-tail SAM domain interaction. JMB. 356(1):142.

Warner, N. (2005). Structure and Function of the SAM Domain in Protein Kinase Signaling. Ph.D. Thesis.

Kwan, J.J.*, Warner, N .*, Pawson, T., Donaldson, L.W. (2004). The solution structure of the S. cerevisiae Ste11 MAPKKK SAM domain and its partnership with Ste50. JMB. 342(2):681.

Park E.K.*, Warner N .*, Bong Y.S., Stapleton D., Maeda R., Pawson T., Daar, I.O. (2004). Ectopic EphA4 receptor induces posterior protrusions via FGF signalling in Xenopus embryos. MBC. 15(4):1647.

Park, E.K., Warner, N ., Mood, K., Pawson, T., Daar, I.O. (2002). Low molecular weight protein tyrosine phosphatase is a positive component of the FGFR signalling pathway. MCB . 22(10): 3404.

Dankort, D., Maslikowski, B., Warner, N ., Kanno, N., Kim, H., Wang, Z., Moran, M., Oshima, R., Cardiff , R. D., Muller, W.J. (2001). Grb2 and Shc adapter proteins play distinct roles in Neu (ErbB-2) induced mammary tumorigenesis: implications for human breast cancer. MCB . 21(5):1540


Awards:

2011-2012 Broad Medical Research Program for Inflammatory Bowel Disease - 2yr Grant

2011 Crohn’s and Colitis Foundation of America - 1yr Grant

2010 Center for Genetics in Health and Medicine Postdoctoral Fellowship

2010 Canadian Society of Immunology Annual Meeting Travel Award

2010 Joint Life Science Institute and Michigan Institute for Clinical Health Research Award


2009-2010 The Miller Fund Award for Innovative Research in Immunology

2004-2005 MacPherson Prize for top graduate student in Microbiology at U of T

2003-2004 Alan Bernstein Graduate Student Fellowship in Research Excellence

2001-2003 Natural Science and Engineering Research Council of Canada PGS-B Scholarship

2000-2001 Ontario Graduate Scholarship and University of Toronto Open Scholarship

1998-2000 Natural Science and Engineering Research Council of Canada PGS-A Scholarship

1994-1998 Canada Scholarship

 

 


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