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Andrew Bowie

Professor
School of Biochemistry and Immunology
Trinity College Dublin
Ireland

Biography

Andrew Bowie obtained his PhD in Biochemistry from Trinity College Dublin in 1997. After postdoctoral training with Prof Luke O'Neill, he was appointed as lecturer in the Department of Pharmacology in UCD, before returning to TCD in 2001 to establish the first and only Immunology undergraduate degree course in Ireland, which he coordinated from 2002 - 2006. He served as Director of Research in the School of Biochemistry and Immunology from 2005 - 2009, and as Head of Immunology from 2011 - 2017. In 2008 he was elected a Fellow of TCD, and in 2014 a member of the Royal Irish Academy. He is actively involved in both undergraduate and postgraduate Immunology teaching, and has graduated 14 PhD students to date. His research discoveries and scholarly activities have significantly contributed to TCD's global reputation as a place of excellence for Immunology teaching and research and in 2017 he was awarded the Irish Society for Immunology Public Lecture Medal for his outstanding contribution to Irish Immunology. He is a global leader in the research fields of innate immunity and viral evasion, and his research occupies a unique space at the interface between virology, immunology and disease pathogenesis. He has raised research funding of >€9m (direct costs to PI) since 2001, from national and international funding agencies including Science Foundation Ireland, the EU and the US National Institutes of Health, and also from private industry. Work in his laboratory has shed light on how pattern recognition receptors (PRRs) recognise pathogens, leading to the induction of interferons and cytokines, which control infection locally as well as coordinating the adaptive immune response. He also investigates how PRRs and other innate immune sensors drive inflammation, and discovered one of the key cellular sensors of DNA in 2010, IFI16, which has subsequently been shown to be critical in understanding viral pathogenesis of diverse viruses including HIV and herpes viruses. He has recently identified novel roles for a number of innate immune proteins in regulating inflammation via cytokine modulation, and is currently exploring their mechanisms of action. His seminal discoveries have redefined our understanding of how pathogens engage with human cells, and he has regularly published research papers, opinion pieces and reviews in leading international journals including Nature Immunology, Immunity, The Journal of Experimental Medicine, Nature Reviews Immunology, PNAS, PLoS Pathogens and The EMBO Journal.

Research Interest

My research focuses on innate immune sensing and signalling mechanisms, and their modulation by viruses. Specifically we are looking at how viruses interact with, and seek to subvert innate immune signalling pathways, such Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs). TLRs and RLRs represent host immune detection systems, in that they have been shown to be involved in recognising pathogens and activating the innate immune response. Through both bioinformatics and functional screens we have identified many poxviral proteins which can antagonise innate immune signalling, and current on-going investigations are seeking to understand the mechanism of action of these proteins and to identify and characterise host target proteins. Further, peptides derived from inhibitory viral proteins are being tested as a route to developing novel anti-inflammatory drugs. Work in my laboratory has shed light on how pattern recognition receptors (PRRs) recognise pathogens, leading to the induction of interferons and cytokines, which control infection locally as well as coordinating the adaptive immune response. We also investigate how PRRs and other innate immune sensors drive inflammation through the recognition of nucleic acid such as mislocalised self-DNA. I have recently identified novel roles for a number of innate immune proteins in regulating inflammation via cytokine modulation, and am currently exploring their mechanisms of action

Publications

  • Horan KA, Hansen K, Jakobsen MR, Holm CK, Søby S, Unterholzner L, Thompson M, West JA, Iversen MB, Rasmussen SB, Ellermann-Eriksen S, Kurt-Jones E, Landolfo S, Damania B, Melchjorsen J, Bowie AG, Fitzgerald KA, Paludan SR, Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors., Journal of immunology (Baltimore, Md. : 1950), 190, (5), 2013, p2311-9

  • Mansur DS, Maluquer de Motes C, Unterholzner L, Sumner RP, Ferguson BJ, Ren H, Strnadova P, Bowie AG, Smith GL, Poxvirus Targeting of E3 Ligase ß-TrCP by Molecular Mimicry: A Mechanism to Inhibit NF-B Activation and Promote Immune Evasion and Virulence., PLoS pathogens, 9, (2), 2013, pe1003183

  • Gürtler, C., Bowie, A.G., Innate immune detection of microbial nucleic acids, Trends in Microbiology, 21, (8), 2013, p413-420

  • Paludan, S., Bowie, A., Immune Sensing of DNA, Immunity , 38, (5), 2013, p870-880

  • Verstak B, Stack J, Ve T, Mangan M, Hjerrild K, Jeon J, Stahl R, Latz E, Gay N, Kobe B, Bowie AG, Mansell A, The TLR signaling adaptor TRAM interacts with TRAF6 to mediate activation of the inflammatory response by TLR4., Journal of leukocyte biology, 96, (3), 2014, p427-36

  • Bowie AG, Rad50 and CARD9, missing links in cytosolic DNA-stimulated inflammation., Nature immunology, 15, (6), 2014, p534-6

  • Wang H, Flannery SM, Dickhöfer S, Huhn S, George J, Kubarenko AV, Lascorz J, Bevier M, Willemsen J, Pichulik T, Schafmayer C, Binder M, Manoury B, Paludan SR, Alarcon-Riquelme M, Bowie AG, Försti A, Weber AN, A coding IRAK2 protein variant compromises Toll-like receptor (TLR) signaling and is associated with colorectal cancer survival., The Journal of biological chemistry, 289, (33), 2014, p23123-31

  • Gürtler C, Carty M, Kearney J, Schattgen SA, Ding A, Fitzgerald KA, Bowie AG, SARM regulates CCL5 production in macrophages by promoting the recruitment of transcription factors and RNA polymerase II to the Ccl5 promoter., Journal of immunology (Baltimore, Md. : 1950), 192, (10), 2014, p4821-32

  • Stack J, Doyle SL, Connolly DJ, Reinert LS, O Keeffe KM, McLoughlin RM, Paludan SR, Bowie AG, TRAM is required for TLR2 endosomal signaling to type I IFN induction., Journal of immunology (Baltimore, Md. : 1950), 193, (12), 2014, p6090-102

  • Stack, J., Doyle, S.L., Connolly, D.J., (...), Paludan, S.R., Bowie, A.G. , TRAM is required for TLR2 endosomal signaling to type I IFN induction, Journal of Immunology, 193, (12), 2014, p6090-6102

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