Chris Moore, PhD, is director of immunology at Arbutus Biopharma. Dr. Moore received his master’s and PhD in physiology from North Carolina State University, Raleigh, NC. Dr. Moore then completed a postdoctoral fellowship at the Lineberger Comprehensive Cancer Center at UNC-Chapel Hill. Dr. Moore held the position of adjunct associate professor at Meredith College, Raleigh, NC, and visiting lecturer at North Carolina State University, Raleigh, NC. Dr. Moore was chief scientist and group leader at Glaxosmithkline (GSK) with research focused on host immune responses to infectious diseases. Following GSK, Dr. Moore joined Arbutus Biopharma as director of immunology with research focused exclusively on hepatitis B virus cure.Following the sequencing of the human genome in 2001, a flurry of research in molecular biology uncovered many previously unknown genes with sequence homology to known immune genes. Chris Moore, PhD’s research was focused on characterizing NLRX1, a unique member of a family of genes named the nod-like receptors (NLRs). Nod proteins are intracellular sentinels for infection with Nod1/Nod2 functioning to mediate intracellular detection of pathogen associated molecular patterns (PAMPs) thereby conferring specificity to host cell innate immune responses. In fact, we now know that much like the toll-like receptors (TLRs), each NLR confers specificity to a unique PAMP and regulates intracellular signaling cascades for pro-inflammatory, antiviral, and cell death responses.
NLRX1 is a Nod-like receptor found to function as a negative regulator of host antiviral responses (Moore, Nature, 2008). Mitochondrial antiviral signaling adaptor (MAVS) protein resides within the mitochondria and mediates RIG-I like receptor (RLR) signaling cascades. Without MAVS, very little type 1 interferon can be produced in response to infection with many classes of viruses. However, this IFN-I response has to be highly regulated as constant activation can lead to host cell death. NLRX1 was identified as a mitochondrial negative regulator of MAVS signaling through its interaction with the leucine rich repeat (LRR) region. Additionally, mice lacking NLRX1 indeed can eliminate viral infection quicker than wildtype animals through rapid upregulation of IFN-I responses but dysregulation of NFkB and IRF3 leads to concomitant systemic upregulation of pro-inflammatory cytokines leading to immunological shock (Moore, Immunity, 2011). Understanding how each NLR regulates these pathways could lead to the identification of drug targets capable of fine tuning host immunity to infectious disease. In fact, infectious disease drug discovery over the last decade has included a close examination of targets important for both the pathogen life cycle and restoration of natural immune function.
- Leivers, A.L., Tallant M., Shotwell J.B., Leivers M.R., McDonald O.B., Gobel J, Creech K.L., Strum S.L., Mathis A., Rogers S., Moore C.B.*, Botyanszki J*, 2014. Discovery of selective small molecule type III phoshatidylinositol 4-kinase alpha (PI4KIIIalpha) inhibitors as anti-hepatitis C (HCV) agents. Journal of Medicinal Chemistry, Mar 13;57(5):2091-106.
- Bojjireddy N., Botyanszki J., Hammond G., Creech D., Peterson R., Kemp D.C., Snead M., Brown R, Morrison A., Wilson S., Harrison S., Moore C.B.*, Balla T*, 2014. Pharmacological and genetic targeting of the PI4KA enzyme reveals its important role in maintaining plasma membrane phosphatidylinositol 4-phosphate and phosphatidylinositol 4, 5-bisphosphate levels. Journal of Biological Chemistry, Feb 28;289(9):6120-32.
- Moore C.B., Allen I.C., 2013. Primary Ear Fibroblasts Derivation from Mice. Methods in Molecular Biology 1031:65-70.
- Llnytska O, Santiana M, Du W.L., Chen Y.H, Belov G, Brinker A, Storch J, Moore C, Dixon J, Altan-Bonnet N, 2013. Endocytic machinery couple altered host cholesterol homeostasis to viral RNA synthesis. Cell Host and Microbe Sep 11;14(3):281-93.
- Lei Y., Wen H., Yu Y., Taxman DJ., Zhang L., Widman D.G., Swanson K.V., Wen K.W., Damania B., Moore C.B., Giguere P.M., Ting J.P., The mitochondrial proteins NLRX1 and TUFM form a complex that regulates type 1 interferon. 2012 Jun 29;36(6): 933-46.
- Allen I.C.*, Moore C.B.*, Schneider M, Lei Y, Davis B.K., Scull M.A., Gris D, Roney K.E., Zimmermann A.G., Bowzard J.B., Ranjan P, Monroe K.M., Vance R.E., Pickles R.J., Sambhara S, Ting J.P., 2011. NLRX1 attenuates inflammatory responses to virus infection by interfering with MAVS and TRAF6. Immunity, 2011 Jun 24; 34(6):854-65.
- Taxman D.J., Holley-Guthrie E.A., Huang M.T., Moore C.B., Bergstralh D.T., Allen I.C., Lei Y, Gris D, Ting J.P., 2011. The NLR adaptor ASC/pycard regulates DUSP10, MAP kinase (MAPK) and chemokine induction independent of the inflammasome. Journal of Biological Chemistry Jun 3; 286(22): 19605-16.
- Arthur J.C., Lich J.D., Ye Z, Allen I.C., Gris D, Wilson J.E., Schneider M, Roney K.E., O’Connor B.P., Moore, C.B., Morrison A, Sutterwala F.S., Bertin J, Koller B.H., Liu Z, Ting J.P., 2010. Cutting edge: NLRP12 controls dendritic and myeloid cell migration to affect contact hypersensitivity. Journal of Immunology Oct 15; 185(8):4515-9.
- Moore C.B., Guthrie E.H., Huang M.T., Taxman D.J., 2010. Short hairpin RNA (shRNA): design, delivery, and assessment of gene knockdown. Methods of Molecular Biology 629:141-58.
- Andersen S.L., Bergstralh D.T., Kohl K.P., LaRocque J.R., Moore C.B., Sekelsky J., 2009. Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombination. Molecular Cell Jul 10;35(1):128-35.
- Moore C.B.*, Lei Y*, Liesman R.M., O’Connor B.P., Bergstralh D.T., Chen Z.J., Pickles R.J., Ting J.P., 2009 MAVS-mediated apoptosis and its inhibition by viral proteins. Plos One Mar 4(5):e5466.
- Allen I.C., Scull M.A., Moore C.B., Holl E.K., McElvania-TeKippe E, Taxman D.J., Guthrie E.H., Pickles R.J., Ting J.P., 2009 The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity Apr 17;30(4):556-65.
- Huang M.T., Taxman D.J., Holley-Guthrie E.A., Moore C.B., Willingham S.B., Madden V., Parsons R.K., Featherstone G.L., Arnold R.R., O’Connor B.P., Ting J.P., 2009 Critical role of apoptotic speck protein containing a caspase recruitment domain (ASC) and NLRP3 in causing necrosis and ASC speck formation induced by Porphyromonas gingivalis in human cells. Journal of Immunology Feb 15;182(4):2395-404.
- O’Connor B.P., Eun S.Y., Ye Z., Zozulya A., Lich J.D., Moore C.B., Iocca H.A., Roney K.E., Wu Q.P., van Deventer H.W., Fabry Z., Ting J.P., 2008. Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses. Proceedings of the National Academy of Sciences Sep;105(35):13015-20.
- Moore C.B. and Ting J.P. 2008. Regulation of mitochondrial antiviral signaling pathways. Immunity Jun;28(6):735-9.
- Moore C.B., Bergstralh D.T, Duncan J.A., Lei Y., Morrison T.E., Zimmermann A.G., Accavitti-Loper M.A., Madden V.J., Sun L., Ye Z., Lich J.D., Heise M.T., Chen Z., Ting J.P-Y., 2008. NLRX1 is a regulator of mitochondrial antiviral signaling. Nature Jan 31;451(7178):573-7.
- Ye, Zhengmao*, Lich J.D.*, Moore C.B., Williams K.L., Duncan J.A., Ting J.P, 2008. ATP-binding to the CATERPILLER protein Monarch-1 is required for its inhibitory function. Molecular and Cellular Biology Mar;28(5):1841-50.
- Moore C.B., Medina M, van Deventer H.W., O’Connor B.P., Cameron S, Taxman D.J., Maile R, Ting J.P., Cairns B.A., 2007. Downregulation of immune signaling genes in patients with large surface burn injury. Journal of Burn Care and Research Nov-Dec;28(6):879-87.
- Lich J.D., Williams K.L., Moore C.B., Arthur J.C., Davis B.K., Taxman D.J., Ting J.P., 2007. Monarch-1 Suppresses Non-Canonical NF-κB activation in Monocytes. Cutting Edge: Journal of Immunology. Feb 1:178(3).
- Bergstralh D.T., Conti B.J., Moore C.B., Brickey W.J., Taxman D.J., and Ting J.P., 2007. Global functional analysis of nucleophosmin in taxol response, cancer, chromatin regulation, and ribosomal DNA transcription. Cell Res. 313(1):65-76.
- Shabman R.S., Morrison T.E., Moore C.B., White L, Suthar M.S., Hueston L., Rulli N., Lidbury B., Ting J.P., Mahalingam S., Heise M.T., 2007. Differential Induction of Type I IFN Responses in Myeloid Dendritic Cells by Mosquito and Mammalian cell-derived Alphaviruses. Journal of Virology. 81(1):237-47.
- Williams K.L., Lich J.D., Duncan J.A., Reed W., Rallabhandi P., Moore C.B., Kurtz S., Coffield M., Accavitti-Loper M.A., Su L., Vogel S.N., Braunstein M., Ting J.P., 2005. The CATERPILLER Protein Monarch-1 Is an Antagonist of Toll-like Receptor-, Tumor Necrosis Factor -, and Mycobacterium tuberculosis-induced Pro-inflammatory Signals. Journal of Biological Chemistry. 280(48):39914-39924.
- Moore, C.B., Siopes T.D., 2005. Enhancement of cellular and humoral immunity following embryonic exposure to melatonin in turkeys (Meleagris gallopavo). General Comparative Endocrinology. 1; 143(2):178-83.
- Moore, C.B., Siopes T.D., 2004. Spontaneous ovarian adenocarcinoma in the domestic turkey breeder hen (Meleagris gallopavo): effects of photoperiod and melatonin. Neuroendocrinology Letters. Feb-Apr;25(1-2):94-101.
- Moore, C.B., Siopes T.D., 2003. Melatonin enhances cellular and humoral immune responses in the Japanese quail (Coturnix coturnix japonica) via an opiatergic mechanism. General Comparative Endocrinology. May; 131(3):258-63.
- Moore, C.B., Siopes T.D., 2003. Immune function in turkey breeder hens during the short day prelighting period and renewal of photosensitivity for egg production. Poultry Science. Jan;82(1):150-4.
- Moore C.B., Siopes T.D., 2002. Effect of melatonin supplementation on the ontogeny of immunity in the Large White turkey poult. Poultry Science. Dec;81(12):1898-903.
- Moore C.B., Siopes T.D., 2002. Melatonin can produce immunoenhancement in Japanese quail (Coturnix coturnix japonica) without prior immunosuppression. General Comparative Endocrinology. Nov;129(2):122-6.
- Moore, C.B., Siopes T.D., Steele C.T., Underwood H., 2002. Pineal melatonin secretion, but not ocular melatonin secretion, is sufficient to maintain normal immune responses in Japanese quail (Coturnix coturnix japonica). General Comparative Endocrinology. May; 126(3):352-8.
- Moore C.B., Siopes T.D., 2000. Effects of lighting conditions and melatonin supplementation on the cellular and humoral immune responses in Japanese quail Coturnix coturnix japonica. General Comparative Endocrinology. Jul;119(1):95-104.
BS – University of North Carolina at Chapel Hill
MS – North Carolina State University
PhD – North Carolina State University
Postdoctoral – University of North Carolina at Chapel Hill