Medicine

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Level 1
Trinity Biomedical Sciences Institute
Trinity College
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Dr. Gareth Brady

Dr. Gareth Brady

Ussher Assistant Professor, Clinical Medicine

https://www.tcd.ie/medicine/thkc/research/inflammation.php/

Biography

My research career to date has been consistently focused on a strategy of using viruses to understand host immunity since I began post-graduate research, completing a PhD in 2005 on the investigation of novel immunoregulatory sequences in the genome of Vaccinia Virus with Professor Luke O'Neill (TCD). I then accepted a six month industrial placement in Opsona Therapeutics leading an independent project to establish several assays and reagents for screening anti-inflammatory compounds partially based on viral strategies of immune evasion and returned to academia. In late 2006, I began a post-doctoral Leukemia and Lymphoma Research (LLRF) fellowship in the Section of Virology, Imperial College London with Professor Paul Farrell analyzing mechanisms of genetic cross-regulation during Epstein Barr Virus (EBV) immune evasion and discovered a complex regulatory control pathway manipulated by the virus to control Runx1 and Runx3 gene expression. On completion of my EBV research, I wished to pursue a long-standing interest to begin research on the only known human-adapted poxvirus Molluscum Contagiosum Virus (MCV) which, despite the fact that the virus appeared incredibly adept at silencing local immunity and inflammation to go largely unnoticed during long term infections, had remained largely unexplored. To pursue this, I returned to Ireland on a Marie Curie career development IEF fellowship under the mentorship of Professor Andrew Bowie in Trinity College Dublin. I became an Ussher Assistant Professor of Vascular Biology in Trinity College Dublin in 2017 and am continuing my research on inflammation signalling and my group is developing novel anti-inflammatory compounds using autoimmune vasculitis as a model for their activity. Additionally, my recent research involves developing seroassay tools for SARS-CoV2 and understanding both the immune response to this virus in COVID-19 and how the virus evades this response.

Publications and Further Research Outputs

  • Brady G, Haas DA, Farrell PJ, Pichlmair A, Bowie AG, Poxvirus Protein MC132 from Molluscum Contagiosum Virus Inhibits NF-B Activation by Targeting p65 for Degradation., Journal of virology, 89, (16), 2015, p8406-15Journal Article, 2015, DOI , TARA - Full Text
  • Brady, G., Haas, D.A., Farrell, P.F., Pichlmair, A. and Bowie, A.G. , Molluscum Contagiosum Virus protein MC005 inhibits NFκB activation by targeting NEMO-regulated IKK activation, The Journal of Virology, 91, (15), 2017, p00545-17Journal Article, 2017, DOI , TARA - Full Text
  • Brady G, Boggan L, Bowie A, O'Neill L.A.J, Erratum: Schlafen-1 causes a cell cycle arrest by inhibiting induction of cyclin D1 (The Journal of Biological Chemistry (2005) 280 (30723-30734) DOI: 10.1074/jbc.M500435200), Journal of Biological Chemistry, 291, (48), 2016, p25278-Journal Article, 2016, DOI , URL
  • Fitzgerald KA, Palsson-McDermott EM, et al, Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction, Nature, 413, (6851), 2001, p78 - 83Journal Article, 2001
  • Fitzgerald, K. A., Palsson-McDermott, E. M., Bowie, A. G., Jefferies, C. A., Mansell, A. S., Brady, G., Brint, E., Dunne, A., Gray, P., Harte, M. T., McMurray, D., Smith, D. E., Sims, J. E., Bird, T. A., and O'Neill, L. A., Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413, 78-83, Nature, 413, 2001, p73 - 83Journal Article, 2001
  • Lucchesi, W., Brady, G., Dittrich-Breiholz, O., Kracht, M., Russ, R., and Farrell, P. J., Differential gene regulation by Epstein-Barr virus type 1 and type 2 EBNA2. , Journal of virology, 82, 2008, p7456 - 7466Journal Article, 2008
  • Brady, G., Whiteman, H. J., Spender, L. C., and Farrell, P. J., Downregulation of RUNX1 by RUNX3 requires the RUNX3 VWRPY sequence and is essential for Epstein-Barr virus-driven B-cell proliferation., Journal of Virology, 83, 2009, p6909 - 6916Journal Article, 2009
  • Brady, G., and Farrell, P. J., RUNX3-mediated repression of RUNX1 in B cells. , Journal of cellular physiology , 221, 2009, p283-2Review Article, 2009
  • Brady, G., MacArthur, G. J., and Farrell, P. J., Epstein-Barr virus and Burkitt lymphoma., J Clin Pathol., 60(12):13, 2007, p1397-402Review Article, 2007
  • Brady G, C.E. Karstegl and P.J. Farrell, Novel function of the unique N terminal region of RUNX1c in B cell growth regulation, Nucleic Acids Research, Feb 1;41(3), 2013, p1555-68Journal Article, 2013
  • Brady G and Bowie AG , Poxviral inhibitors of NFκB, Cytokine and Growth Factor Reviews, Oct;25(5), 2014, p611-2Review Article, 2014
  • Brady G, Hass DA, Pichlmair A, Farrell PJ, and Bowie AG. , Human Poxvirus protein MC132 from Molluscum Contagiosum Virus inhibits NFκB activation by targeting p65 for degradation., Journal of Virology , (89), 2015, p8406-15Journal Article, 2015, DOI , TARA - Full Text
  • Dearbhaile Dooley, Mirjan M. van Timmeren, Vincent P. O'Reilly, Gareth Brady, Eoin C. O'Brien, Barbara Fazekas, Fionnuala B. Hickey, Emma Leacy, Charles D. Pusey, Frederick W.K. Tam, Thomas Mehrling, Peter Heeringa and Mark A. Little, Alkylating histone deacetylase inhibitors may have therapeutic value in experimental myeloperoxidase-ANCA vasculitis, Kidney International, 94, (5), 2018, p926 - 993Journal Article, 2018, DOI , TARA - Full Text
  • C. Jefferies, A. Bowie, G. Brady, E. L. Cooke, X. Li and L. A. O'Neill, Transactivation by the p65 subunit of NF-kappaB in response to interleukin-1 (IL-1) involves MyD88, IL-1 receptor-associated kinase 1, TRAF-6, and Rac1, Molecular and cellular biology, 21, (14), 2001, p4544-52Journal Article, 2001, URL , TARA - Full Text
  • Phelan T, Little MA, Brady G., Targeting of the cGAS-STING system by DNA viruses., Biochemical Pharmacology, 174:113831, 2020Journal Article, 2020, URL
  • Ui Mhaonaigh, A., Coughlan, A. M., Dwivedi, A., Hartnett, J., Cabral, J., Moran, B., Brennan, K., Doyle, S. L., Hughes, K., Lucey, R., Floudas, A., Fearon, U., McGrath, S., Cormican, S., De Bhailis, A., Molloy, E. J., Brady, G., & Little, M. A., Low Density Granulocytes in ANCA Vasculitis Are Heterogenous and Hypo-Responsive to Anti-Myeloperoxidase Antibodies., Frontiers in immunology, 10, (2603), 2019Journal Article, 2019, DOI , TARA - Full Text
  • Lawler C, Brady G. , Poxviral Targeting of Interferon Regulatory Factor Activation. , Viruses, 12, (10), 2020Journal Article, 2020, DOI , TARA - Full Text
  • David Casserly, Lili Gu, Gareth Brady, Susan Carpenter, Adrian P. Bracken, Katherine A Fitzgerald, Leonie Unterholzner, and Andrew G Bowie., MNDA controls the pathogen-stimulated type I IFN cascade in human monocytes by transcriptional regulation of IRF7., Nature Communications, 2020Journal Article, 2020
  • Leacy E, Brady G, Little MA., Pathogenesis of ANCA-associated vasculitis: an emerging role for immunometabolism., Rheumatology, 59, (Supplement 3), 2020Journal Article, 2020, DOI
  • Emma Leacy, Gareth Brady, Niall Conlon, Jennifer Scott, Jean Dunne, Thomas Phelan, William J McCormack, Matthew D Griffin, Alan Kennedy, Alyssa Verrelli, Eamonn Molloy, Declan O'Sullivan, Julie Power, Michael Clarkson, Lina Zgaga, Michelle O'Saughnessy, Mark A Little, Study Protocol for DeCOmPRESS: Defining the Disease Course and Immune Profile of COVID-19 in the Immunosuppressed Patient, HRB Open Res, 4, (6), 2021Journal Article, 2021, DOI , TARA - Full Text
  • Dyer AH, Noonan C, McElheron M, Batten I, Reddy C, Connolly E, Pierpoint R, Murray C, Leonard A, Higgins C, Reilly P, Boran G, Phelan T, McCormack W, O'Neill D, Fallon A, Brady G, O'Farrelly C, Bourke NM, Kennelly SP., Previous SARS-CoV-2 Infection, Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents, Journal of the American Medical Directors Association, 2022Journal Article, 2022, DOI , URL
  • AL Hamrashdi, M. and Brady, G., Regulation of IRF3 activation in human antiviral signaling pathways, Biochemical Pharmacology, 200, (115026), 2022Journal Article, 2022, DOI , URL
  • Phelan, T. and Dunne, J. and Conlon, N. and Cheallaigh, C.N. and Abbott, W.M. and Faba-Rodriguez, R. and Amanat, F. and Krammer, F. and Little, M.A. and Hughes, G. and Bergin, C. and Kerr, C. and Sundaresan, S. and Long, A. and McCormack, W. and Brady, G., Article dynamic assay for profiling anti-sars-cov-2 antibodies and their ace2/spike rbd neutralization capacity, Viruses, 13, (7), 2021Journal Article, 2021, DOI , URL
  • Maguire, F. and Murphy, M.E. and Rourke, M. and Morgan, F. and Brady, G. and Byrne, E. and O†Callaghan, M.E., A cross-sectional study of antibiotic prescribing for childhood upper respiratory tract infections in irish general practice, Irish Medical Journal, 111, (10), 2018, p835Journal Article, 2018, URL
  • Kusiak, A. and Brady, G., Bifurcation of signalling in human innate immune pathways to NF-kB and IRF family activation, Biochemical Pharmacology, 205, (115246), 2022Journal Article, 2022, DOI , URL
  • McGrath, J. and Kenny, C. and Nielsen, C.S. and Domegan, L. and Walsh, C. and Rooney, P. and Walsh, S. and Conlon, N. and Brady, G. and Ibrahim, A. and Dunne, J. and McCormack, W. and Corcoran, N. and Allen, N. and Fleming, C. and Bergin, C., SARS-CoV-2 epidemiology, antibody dynamics, and neutralisation capacity in Irish healthcare workers in the era of booster COVID-19 vaccinations, Frontiers in Medicine, 10, (1078022), 2023Journal Article, 2023, DOI , URL
  • Phelan, T. and Lawler, C. and Pichlmair, A. and Little, M.A. and Bowie, A.G. and Brady, G., Molluscum Contagiosum Virus Protein MC008 Targets NF-kB Activation by Inhibiting Ubiquitination of NEMO, Journal of Virology, 97, (3), 2023Journal Article, 2023, DOI , URL
  • Gordon Greville, Sinead Cremen, Shauna O'Neill, Sarah Azarian, Gareth Brady, William McCormack, Adam H Dyer, Nollaig M Bourke, Olivier Touzelet, David Courtney, Ultan F Power, Paul Dowling, Tom K Gallagher, Connor G G Bamford, Mark W Robinson, Type 1 interferon auto-antibodies are elevated in patients with decompensated liver cirrhosis, Clin Exp Immunol ., 2023Journal Article, 2023
  • Leacy, E., Batten, I., Sanelli, L., McElheron, M., Brady, G., Little, M.A., Khouri, H., Optimal LC-MS metabolomic profiling reveals emergent changes to monocyte metabolism in response to lipopolysaccharide, Frontiers in Immunology, 14, 2023Journal Article, 2023, DOI
  • McGrath, J. and O'Doherty, L. and Conlon, N. and Dunne, J. and Brady, G. and Ibrahim, A. and McCormack, W. and Walsh, C. and Domegan, L. and Walsh, S. and Kenny, C. and Allen, N. and Fleming, C. and Bergin, C., Point of care detection of SARS-CoV-2 antibodies and neutralisation capacityâ€"lateral flow immunoassay evaluation compared to commercial assay to inform potential role in therapeutic and surveillance practices, Frontiers in Public Health, 11, (1245464), 2023Journal Article, 2023, DOI , URL
  • Leacy EJ, Teh JW, O'Rourke AM, Brady G, Gargan S, Conlon N, Scott J, Dunne J, Phelan T, Griffin MD, Power J, Mooney A, Naughton A, Kiersey R, Gardiner M, O'Brien C, Mullan R, Flood R, Clarkson M, Townsend L, O'Shaughnessy M, Dyer AH, Moran B, Fletcher JM, Zgaga L, Little MA, RITA Ireland Vasculitis Biobank., Effect of Immunosuppression on the Immune Response to SARS-CoV-2 Infection and Vaccination., International journal of molecular sciences, 25, (10), 2024, p5239Journal Article, 2024, DOI
  • Al Hamrashdi, M. and Perez, C.S. and Haas, D.A. and Vishwakarma, J. and Pichlmair, A. and Bowie, A.G. and Brady, G., Molluscum contagiosum virus protein MC089 inhibits interferon regulatory factor 3 activation, Journal of General Virology, 105, (8), 2024Journal Article, 2024, DOI , URL
  • Schaler, L. and Ghanim, M. and Guardiola, J. and Kaulsay, J. and Ibrahim, A. and Brady, G. and McCormack, W. and Conlon, N. and Kelly, V.P. and Wingfield, M. and Glover, L., Impact of COVID-19 vaccination on seminal and systemic inflammation in men, Journal of Reproductive Immunology, 164, (104287), 2024Journal Article, 2024, DOI , URL
  • Townsend, L. and Dunne, J. and Sui, J. and Sanchez Perez, C. and McElheron, M. and Reid, C. and McCormack, W. and Bergin, C. and Fleming, C. and O'Farrelly, C. and Brady, G. and Conlon, N., Immune response in vaccinated healthcare workers with frequent COVID-19 infections is characterised by blunted IFNγ and IL-2 responses to SARS-CoV-2 variants, Clinical Immunology, (110371), 2024Journal Article, 2024, DOI , URL
  • Brady G, Boggan L, Bowie A and O'Neill LA, Schlafen-1 causes a cell cycle arrest by inhibiting induction of cyclin D1, Journal of Biological Chemistry, 280, (35), 2005, p30723 - 30734Journal Article, 2005, DOI , TARA - Full Text
  • Gubster C, Goodbody R, Ecker A, Brady G, O'Neill LA, Jacobs N, Smith GL., Camelpox virus encodes a schlafen-like protein that affects orthopoxvirus, Journal of General Virology, 88, (6), 2007, p1667-1676Journal Article, 2007, DOI , TARA - Full Text
  • Brady, Gareth Bowie, Andrew G., Innate immune activation of NFκB and its antagonism by poxviruses, Cytokine & Growth Factor Reviews, 2014Journal Article, 2014, DOI , TARA - Full Text
  • Brady, G., Macarthur, G. J., and Farrell, P. J., Epstein-Barr virus and Burkitt lymphoma. , Postgraduate medical Journal, 84, 2008, p372-377Review Article

Research Expertise

My interests are centered on Viral Immune Evasion, understanding novel aspects of inflammatory signalling and Innate Immunity an the development of Novel anti-inflammatory therapeutics. My research Group the Translational Inflammation Research Group (TIRG) which currently consists of one research assistant. Since establishing my lab, I graduated 4 PhD students and hosted two post-doctoral researchers, 4 research assistants and a 5-month Spanish Erasmus student. My SFI-Frontiers funded research focuses on understanding how the human-adapted poxvirus Molluscum Contagiosum Virus evades human immunity and the therapeutic potential of peptides derived from the virus. Our Allergan and SFI-funded COVID research is focused on developing seroassay tools for SARS-CoV to monitor pre- and post-vaccination immune responses in the population in addition to understanding how the virus is detected by and evades the immune system. Our Maeth Foundation and Vasculitis UK funded research focuses on understanding the innate immune signalling of autoantibody-stimulated inflammation in monocytes in an ANCA vasculitis model of disease.

Immunology, Genetics, Microbiology,

Recognition

  • Best Basic Science Presentation, Irish Nephrology Society meeting 2018
  • Young Investigator Award International RUNX Conference, Ja Jolla, San Diego 2011
  • Allergan Innovation Award 2020 2020
  • Provost's Award for Excellence in Supervision of Research Students 2022
  • Roche Gold Medal for Best Researcher. 2015
  • National Irish Times Science writing award 2000
  • Best Poster Presentation Prize, Irish Society for Immunology (ISI) meeting 2015
  • Best Research Presentation Prize NF Kappa B 2014 workshop at Pitlochry. 2014
  • Best Research Prize, Irish Society for Immunology (ISI) meeting 2014
  • Irish Society of Immunology (also on the Committee, Head of Outreach) Present
  • Biochemical Society Present