B.A. Biology The Colorado College
Ph.D. Immunology Baylor College of Medicine
Postdoctoral Fellow Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
NLRs, novel proteins involved in immunity, inflammation and cell death:
Discrimination by the vertebrate host of molecular moieties derived from pathogenic insult requires the coordination of manifold systems of receptors and sensors that affect transcriptional and post-translational programs that are necessary for host defense and resolution of infection and inflammation. Coordinately, pathogens have evolved mechanisms to counteract host surveillance and effector responses in a constant give and take in host-parasite interactions. Coordination of recognition, initiation, and elaboration of signals results in resolution, whereas dysregulation results in disease.
Nucleotide-binding domain, leucine-rich repeat containing proteins (NLRs) are a recently discovered multigene family that is involved in vertebrate immunity and inflammation. To wit, mutations in NLRs are associated with diverse genetic diseases characterized by either uncontrolled inflammation or immunosuppression. Therefore understanding the molecular mechanisms of the pathways associated with these proteins is of great interest. My interests are restricted to two known members of the NLR gene family (NLRP3 and NOD2) as well as a recently characterized member NLRC5. Projects in my laboratory revolve around understanding how these proteins function in the vertebrate host:
· Structure function analysis of NOD2 interactions with muramyl-dipeptide
· High throughput screen of NLRC5 binding partners using yeast two-hybrid technology
· Biochemical analysis of nucleotide binding in NLR proteins
· In vivo role of NLR-related proteins in sterile inflammation
· Toxin-dependent inflammasome activation
Data derived from these projects will help further our understanding of the role of NLR proteins in host defense and disease pathology. The field of NLR biology has become exceptionally competitive but immensely exciting. Students with an interest in human diseases, immunology/cell biology and biochemistry are encouraged to contact me regarding potential independent research possibilities.
Pothlichet J, Meunier I, Davis BK, Ting JP-Y, Skamene E, von Messling V and Vidal SM. Type I IFN Triggers RIG-I/TLR3/NLRP3-dependent Inflammasome Activation in Influenza A Virus Infected Cells. 2013 PLoS Pathogens 9(4).
Schneider M, Zimmermann AG, Roberts RA, Zhang L, Swanson KV, Wen H, Davis BK, Allen IC, Holl EK, Ye Z, Rahman AH, Conti BJ, Eitas TK, Koller BH, Ting JP. The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB. Nat Immunol. 2012 Aug 5.
Robbins, GR, Truax, AD, Davis, BK, Zhang L, Brickey WJ, Ting JP. Regulation of class I major histocompatibility complex (MHC) by nucleotide-binding domain, leucine-rich repeat containing (NLR) proteins. Journal of Biological Chemistry 2012 Jul 13;287(29):24294-303
Mo, JY, Boyle, JP, Howard, CB, Monie, TP, Davis, BK*, Duncan, JA*. Pathogen sensing by nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is mediated by direct binding to muramyl dipeptide and ATP. Journal of Biological Chemistry 2012 Jun 29;287(27):23057-67 (*=co-contributing authors)
Allen, IC, Wilson, JE, Schneider, M, Lich, JD, Roberts, RA, Arthur, JC, Woodford, R-MT, Davis, BK, Uronis, JM, Herfarth, HH, Jobin, C, Rogers, AB, Ting, JP-Y. NLRP12 Suppresses Colon Inflammation and Tumorigenesis through the Negative Regulation of Noncanonical NF-kB Signaling. Immunity. 2012 May 25;36(5):742-54
Roney, KE, O'Connor, BP, Wen, H, Holl, EK, Guthrie, EH, Davis, BK, Jones, SW, Jha, S, Sharek, L, Garcia-Mata, R, Bear, JE and Ting, JP. Plexin-b2 negatively regulates macrophage motility, rac and cdc42 activation. PLoS One 2011; 6(9):e24795. Epub 2011 Sep 23
Wang, JG, Williams, JC, Davis, BK, Ting, JPY, Jacobson, K and Mackman, N. Monocyte-derived Microparticles Activate Endothelial cells in an IL-1β-dependent Manner Blood 2011 Aug 25;118(8):2366-74.
Jorgensen, I, Bednar M, Amin, V, Davis, BK, Ting, JPY, McCafferty, D, Valdivia, RH. The Chlamydia protease CPAF regulates host and bacterial proteins to maintain vacuole integrity and promote virulence. (Cell, Host and Microbe 2011 Jul 21;10(1):21-32)
Allen, IC, Moore, CB, Schneider, M, Yu, L, Davis, BK, Scull, MA, Gris, D, Roney, KE, Zimmermann, AG, Bowzard, JB, Ranjan, P, Monroe, KM, Vance, RE, Pickles, RJ, Sambhara, S, Ting, JPY. NLRX1 interacts with TRAF6 and functions as a negative regulator of the innate immune response to Influenza A virus infection. Immunity Jun 24;34(6):854-65
Gregory, SM, Davis, BK, West, JA, Taxman, DJ, Matsuzawa, S, Reed, JC, Ting, JPY and Damania, B. Discovery of a viral NLR homolog encoded by KSHV that inhibits the inflammasome. (Science 21 January 2011: 330-334)
Davis, BK, Roberts, RA, Huang, MT, Willingham, SB, Conti, BJ, Brickey, WJ, Kwan, M, Taxman, DJ, Accavitti-Loper, MA, Duncan, JA, Ting, JPY. NLRC5-dependent activation of the inflammasome. (Cutting Edge at J Immunol:2011 Feb 1;186(3):1333-7)
Davis, BK, Wen, HT and Ting, JPY. The inflammasome NLRs in immunity, inflammation and associated diseases. (Annu Rev Immuno 2011(29): 707-735: RIA Decmeber 30, 2010)
McNally, RS, Davis, BK, Clements, CM, Accavitti-Loper, MA, Mak, TM, Ting, JPY. DJ-1 enhances cell survival through the direct binding of Cezanne, a negative regulator of NF-kB. J Biol Chem 2011 Feb 11;286(6):4098-106
Huang, MTZ, Mortensen, BL, Taxman, DT, Craven, R, Taft-Benz, R, Keijek, T, Fuller, JR, Davis, BK, Allen, IC, Brickey, WJ, Gris, D, Wen, HT, Kawula, TH, Ting, JPY. Deletion of ripA alleviates suppression of the inflammasome and MAP kinase by Francisella tularensis J Immunol. 2010 Nov 1;185(9):5476-85
Davis, BK, Ting JPY. NLRP3 has a sweet tooth. Nat Immunol. 2010 Feb;11(2):105-6. Review
Ting JP, Lovering RC, Alnemri ES, Bertin J, Boss JM, Davis BK, Flavell RA, Girardin SE, Godzik A, Harton JA, Hoffman HM, Hugot JP, Inohara N, Mackenzie A, Maltais LJ, Nunez G, Ogura Y, Otten LA, Philpott D, Reed JC, Reith W, Schreiber S, Steimle V, Ward PA. The NLR gene family: a standard nomenclature. Immunity. 2008 Mar;28(3):285-7
van Deventer HW, Ping Wu, Q, Bergstralh, DT, Davis, BK, Ting, JPY, Serody, JS.
CCR5 on pulmonary myofibroblasts facilitates migration and promotes metastasis via MMP9 Am J Pathol. 2008 Jul;173(1):253-64
Lich JD, Williams KL, Moore CB, Arthur JC, Davis BK, Taxman DJ, Ting JP. Monarch-1 suppresses non-canonical NF-kB activation and p52-dependent chemokine expression in monocytes. J Immunol. 2007 Feb 1;178(3):1256-60
Wanahita A, Davis B, Hamill RJ, Goldsmith EA, Rodgers JR, Cook RG, Lamphear JG, Musher DM. Clostridium difficile lacks detectable superantigen activity. FEMS Immunol Med Microbiol. 2006 Jul;47(2):275-7
Conti, BJ, Davis, BK, Zhang, Z, O’Connor, W, Williams, KL and Ting, JP-Y. CATERPILLER16.2 (CLR16.2): A novel NBD/LRR family member that negatively regulates T cell function. J. Biol. Chem. 2005 May 6;280(18):18375-85
Ting, JP-Y and Davis, BK. CATERPILLER: A novel gene family important in immunity, cell death and diseases. Annu Rev Immunol. 2005; 23:387-414
Wu, H, Rodgers, JR, Perrard, X-YD, Perrard, JL, Prince, JE, Abe, Y, Davis, BK, Dietsch, G, Smith, CW and Ballantyne, CM. Deficiency of CD11b or CD11d results in phenotypic changes in T cells leading to reduced staphylococcal enterotoxin-induced T cell response. J Immunol. 2004 Jul 1;173(1):297-306
Davis, BK, Cook, RG, Rich RR, Rodgers JR. Hyperconservation of the putative antigen recognition site of the MHC class I-b molecule TL in the subfamily Murinae: evidence that thymus leukemia antigen is an ancient mammalian gene. J Immunol 2002 Dec 15;169(12):6890
Doyle, CK, Davis, BK, Cook, RG, Rich, RR, and Rodgers, JR. Hyperconservation of the N-formyl peptide binding site of M3: evidence that M3 is an old eutherian molecule with conserved recognition of a pathogen-associated molecular pattern. J Immunol 2003 171: 836-844
Ling, P, Meyer CF, Redmond, LP, Shui J, Davis B, Rich R, Hu, M, Wange, R, Tan TH. Involvement of Hematopoietic Progenitor Kinase 1 in T cell Receptor Signaling J Biol Chem. 2001 Jun 1;276(22):18908-14