Sarah Doyle


Sarah Doyle

Assistant Professor of Immunology

Sarah completed her PhD on Toll-like Receptor (TLR) signalling pathways under the supervision of Professor Luke O’Neill in the Dept. of Biochemistry, Trinity College Dublin (TCD) in 2007. Since then Sarah’s scientific interests have centred on the molecular dialogue associated with how the immune system recognises injury, reacts, and directs an inflammatory response to resolve insult. One major aspect of her research focuses on elucidating the cellular mechanisms and signalling events that regulate the effects of Pattern Recognition Receptor (PRR) responses, in particular the TLRs and NLRs of the innate immune system, to both pathogen-derived and endogenous damage-associated immunomodulators. Sarah worked as a post-doctoral research fellow in the School of Biochemistry and Immunology in TCD between 2007 – 2012 with time spent in NTNU, Norway in 2008 and again in 2010. In 2012, Sarah was recruited as an Assistant Professor and Lecturer in Immunology in the School of Medicine with a position in the Dept. of Clinical Medicine.

Sarah Doyle

Assistant Professor of Immunology

Dr. Kiva Brennan
Position: Post-Doctoral Research Fellow
kbrenna@tcd.ie

Role:
Kiva studies immune signalling pathways activated after infection or injury in neonates and infants.

Developmental changes in Pattern Recognition Receptor activity as the innate immune system develops from birth through infancy into childhood and adolescence.

Developmental changes in Pattern Recognition Receptor activity as the innate immune system develops from birth through infancy into childhood and adolescence. Summary: Human neonates and young infants are more vulnerable to certain infectious agents than older children and adults, and are especially susceptible to infections with intracellular pathogens. Due to the requirement of the adaptive immune system for immunological experience, the innate immune system, and its Pattern Recognition Receptors (PRRs), represent the critical front-line defense against these pathogens. This project aims to assess which pathways activated by these PRRs are altered in the “immature” innate immune system and furthermore, how, and at what stage, they develop into a mature innate response; information generated should lead to improved age-appropriate therapies for infectious and inflammatory childhood diseases.

Improving vaccine responses in the paediatric population by harnessing Pattern Recognition Receptor responses to promote Th1- and Th17-cell polarisation.

After clean water, vaccination is the most effective public-health intervention, yet despite global efforts, 2 million children die each year from infectious diseases before they reach 1 year. The challenge to early-life vaccination is that immune-responsiveness varies with age with evidence suggesting that responses elicited by the immune system of infants and young children are compromised, when compared with those in adults. This is due to the fact that the molecular rules that govern how the adult immune system responds to certain stimuli, called “adjuvants”, do not necessarily apply to the “developmentally-young” immune system. This project aims to build on our previous NCRC funded research to assess which immune-responses are functional in infants and children and, furthermore, to pinpoint the stimuli that result in a robust immune response. Information generated will lead to improved age-appropriate “adjuvants” for vaccine-preventable diseases potentially eliminating the need for booster injections and closing the “window of vulnerability” preventing life-threatening invasive infection in early life.



The list of publications below is automatically derived from MEDLINE/PubMed. As a result, there may be incorrect or missing publications.

Brennan K, Lyons C, Fernandes P, Doyle S, Houston A, Brint E, 2018 Dec 11, Engagement of Fas differentially regulates the production of LPS-induced pro-inflammatory cytokines and type I Interferons. FEBS J, DOI: 10.1111/febs.14727
Brennan K, O'Leary BD, Mc Laughlin D, Breen EP, Connolly E, Ali N, O'Driscoll DN, Ozaki E, Mahony R, Mulfaul K, Ryan AM, Ni Chianain A, McHugh A, Molloy EJ, Hogan AE, Paran S, McAuliffe FM, Doyle SL, 2018 Aug 15, Type 1 IFN Induction by Cytosolic Nucleic Acid Is Intact in Neonatal Mononuclear Cells, Contrasting Starkly with Neonatal Hyporesponsiveness to TLR Ligation Due to Independence from Endosome-Mediated IRF3 Activation. J Immunol, DOI: 10.4049/jimmunol.1700956
Mulfaul K, Rhatigan M, Doyle S, 2018, Toll-Like Receptors and Age-Related Macular Degeneration. Adv Exp Med Biol, DOI: 10.1007/978-3-319-75402-4_3
Connolly E, Rhatigan M, O'Halloran AM, Muldrew KA, Chakravarthy U, Cahill M, Kenny RA, Doyle SL, 2018 Dec, Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population. Br J Ophthalmol, DOI: 10.1136/bjophthalmol-2017-311673
Theodoropoulou S, Copland DA, Liu J, Wu J, Gardner PJ, Ozaki E, Doyle SL, Campbell M, Dick AD, 2017 Jan, Interleukin-33 regulates tissue remodelling and inhibits angiogenesis in the eye. J Pathol, DOI: 10.1002/path.4816
Husebye H, Doyle SL, 2016, Using Confocal Microscopy to Investigate Intracellular Trafficking of Toll-Like Receptors. Methods Mol Biol, DOI: 10.1007/978-1-4939-3335-8_4
Doyle SL, López FJ, Humphries P, Adamson P, Campbell M, 2015 Dec, Author Response: The Role of IL-18 in the Treatment of AMD. Invest Ophthalmol Vis Sci, DOI: 10.1167/iovs.15-18714
Doyle SL, López FJ, Celkova L, Brennan K, Mulfaul K, Ozaki E, Kenna PF, Kurali E, Hudson N, Doggett T, Ferguson TA, Humphries P, Adamson P, Campbell M, 2015 Aug, IL-18 Immunotherapy for Neovascular AMD: Tolerability and Efficacy in Nonhuman Primates. Invest Ophthalmol Vis Sci, DOI: 10.1167/iovs.15-17264
Celkova L, Doyle SL, Campbell M, 2015 Jan 14, NLRP3 Inflammasome and Pathobiology in AMD. J Clin Med, DOI: 10.3390/jcm4010172
Ozaki E, Campbell M, Doyle SL, 2015, Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives. J Inflamm Res, DOI: 10.2147/JIR.S51250
Doyle SL, Adamson P, López FJ, Humphries P, Campbell M, 2014 Dec 23, Interleukin-18 bioactivity and dose: data interpretation at a crossroads. Invest Ophthalmol Vis Sci, DOI: 10.1167/iovs.14-15786
Doyle SL, Adamson P, López FJ, Humphries P, Campbell M, 2014 Dec, Reply to IL-18 is not therapeutic for neovascular age-related macular degeneration. Nat Med, DOI: 10.1038/nm.3741
Stack J, Doyle SL, Connolly DJ, Reinert LS, O'Keeffe KM, McLoughlin RM, Paludan SR, Bowie AG, 2014 Dec 15, TRAM is required for TLR2 endosomal signaling to type I IFN induction. J Immunol, DOI: 10.4049/jimmunol.1401605
Campbell M, Doyle S, Humphries P, 2014 Oct, IL-18: a new player in immunotherapy for age-related macular degeneration? Expert Rev Clin Immunol, DOI: 10.1586/1744666X.2014.950231
Doyle SL, Ozaki E, Brennan K, Humphries MM, Mulfaul K, Keaney J, Kenna PF, Maminishkis A, Kiang AS, Saunders SP, Hams E, Lavelle EC, Gardiner C, Fallon PG, Adamson P, Humphries P, Campbell M, 2014 Apr 2, IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration. Sci Transl Med, DOI: 10.1126/scitranslmed.3007616
Ozaki E, Campbell M, Kiang AS, Humphries M, Doyle SL, Humphries P, 2014, Inflammation in age-related macular degeneration. Adv Exp Med Biol, DOI: 10.1007/978-1-4614-3209-8_30
Kenny EF, Quinn SR, Doyle SL, Vink PM, van Eenennaam H, O'Neill LA, 2013, Bruton's tyrosine kinase mediates the synergistic signalling between TLR9 and the B cell receptor by regulating calcium and calmodulin. PLoS One, DOI: 10.1371/journal.pone.0074103
Doyle SL, Shirey KA, McGettrick AF, Kenny EF, Carpenter S, Caffrey BE, Gargan S, Quinn SR, Caamaño JH, Moynagh P, Vogel SN, O'Neill LA, 2013 Aug 30, Nuclear factor κB2 p52 protein has a role in antiviral immunity through IκB kinase epsilon-dependent induction of Sp1 protein and interleukin 15. J Biol Chem, DOI: 10.1074/jbc.M113.469122
Campbell M, Doyle SL, 2013 Sep, An eye on the future of inflammasomes and drug development in AMD. J Mol Med (Berl), DOI: 10.1007/s00109-013-1050-0
Doyle SL, Campbell M, Ozaki E, Salomon RG, Mori A, Kenna PF, Farrar GJ, Kiang AS, Humphries MM, Lavelle EC, O'Neill LA, Hollyfield JG, Humphries P, 2012 May, NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components. Nat Med, DOI: 10.1038/nm.2717
Doyle SL, Husebye H, Connolly DJ, Espevik T, O'Neill LA, McGettrick AF, 2012 Feb 28, The GOLD domain-containing protein TMED7 inhibits TLR4 signalling from the endosome upon LPS stimulation. Nat Commun, DOI: 10.1038/ncomms1706
McCoy CE, Sheedy FJ, Qualls JE, Doyle SL, Quinn SR, Murray PJ, O'Neill LA, 2010 Jul 2, IL-10 inhibits miR-155 induction by toll-like receptors. J Biol Chem, DOI: 10.1074/jbc.M110.102111
O'Neill LA, Bryant CE, Doyle SL, 2009 Jun, Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev, DOI: 10.1124/pr.109.001073
Palsson-McDermott EM, Doyle SL, McGettrick AF, Hardy M, Husebye H, Banahan K, Gong M, Golenbock D, Espevik T, O'Neill LA, 2009 Jun, TAG, a splice variant of the adaptor TRAM, negatively regulates the adaptor MyD88-independent TLR4 pathway. Nat Immunol, DOI: 10.1038/ni.1727
Doyle SL, Jefferies CA, Feighery C, O'Neill LA, 2007 Dec 21, Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem, DOI: 10.1074/jbc.M707682200
Doyle SL, O'Neill LA, 2006 Oct 30, Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. Biochem Pharmacol, DOI: 10.1016/j.bcp.2006.07.010
Gray P, Dunne A, Brikos C, Jefferies CA, Doyle SL, O'Neill LA, 2006 Apr 14, MyD88 adapter-like (Mal) is phosphorylated by Bruton's tyrosine kinase during TLR2 and TLR4 signal transduction. J Biol Chem, DOI: 10.1074/jbc.M508892200

Name:Professor Ed Lavelle
DepartmentBiochemistry and Immunology
Institution:TCD
Country:Ireland
Name:Professor Andrew Bowie
DepartmentBiochemistry and Immunology
Institution:TCD
Country:Ireland
Name:Professor Fionnuala McAuliffe
DepartmentObstetrics
Institution:UCD
Country:Ireland
Name:Mr Sri Paran
DepartmentSurgery
Institution:UCD
Country:Ireland
Name:Dr Ricarrdo Natoli
DepartmentCollege of Health and Medicine
Institution:Australian National University
Country:Australia
Name:Professor Rob Mullins
DepartmentMolecular Physiology and Biophysics
Institution:Iowa University
Country:USA
Name:Dr Harald Husebye
DepartmentClinical and Molecular Medicine
Institution:NTNU
Country:Norway