Dr James McLaren
Uwch Ddarlithydd mewn Imiwnoleg
- McLarenJE@caerdydd.ac.uk
- +44 29207 44431
- Adeilad Ymchwil Cardiofasgwlaidd Syr Geraint Evans, Ystafell 2/04, Ysbyty Athrofaol Cymru, Parc y Mynydd Bychan, Caerdydd, CF14 4XN
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwyg
Mae fy niddordebau ymchwil yn canolbwyntio ar ddeall sut mae ymatebion imiwnedd addasol, sy'n cael eu gyrru gan gelloedd T, yn ymateb i heintiau firws a bacteria a hefyd sut mae micro-organebau pathogenig yn defnyddio strategaethau esblygol i osgoi celloedd T. Ar ben hynny, mae gen i ddiddordeb brwd mewn darganfod sut mae'r math hwn o imiwnedd cellog yn cael ei reoleiddio gan signalau biolegol (sytocinau) a sut y gall ansefydlogi pan fydd ymatebion imiwnedd byd-eang yn cael eu anghydbwyso, fel mewn sepsis.
Ar hyn o bryd rwy'n ymwneud â "Project Sepsis", cydweithrediad ymchwil ar draws disgyblaethau meddygaeth a gwyddonol sydd wedi'i sefydlu i fynd i'r afael ag angen meddygol brys am ddiagnosis cywir, cyflym sy'n canfod yr achos heintus sy'n sail i ddechrau sepsis. Yma, nod allweddol yw datgysylltu'r mecanweithiau imiwnolegol sy'n ysgogi atal imiwnedd addasol mewn sepsis gyda'r bwriad o helpu i wella diagnosis ac i lywio dyluniad ymyriadau therapiwtig newydd.
Cyhoeddiad
2024
- Davies, K. and McLaren, J. 2024. Destabilisation of T cell-dependent humoral immunity in sepsis. Clinical Science 138(1), pp. 65-85. (10.1042/CS20230517)
2023
- Oruganti, S. et al. 2023. Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study. BMJ Open 13, article number: e067002. (10.1136/bmjopen-2022-067002)
- Shepherd, F. R. et al. 2023. The superantigens SpeC and TSST-1 specifically activate TRBV12-3/12-4+ memory T cells. Communications Biology 6, article number: 78. (10.1038/s42003-023-04420-1)
2022
- Goncharov, M. et al. 2022. VDJdb in the pandemic era: a compendium of T cell receptors specific for SARS-CoV-2. Nature Methods 19(9), pp. 1017–1019. (10.1038/s41592-022-01578-0)
- Pymm, P. et al. 2022. Epitope length variants balance protective immune responses and viral escape in HIV-1 infection. Cell Reports 38(9), article number: 110449. (10.1016/j.celrep.2022.110449)
- Misheva, M. et al. 2022. Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation. Nature Communications 13(1), article number: 139. (10.1038/s41467-021-27766-8)
2021
- Chakraborty, M. et al. 2021. nSeP: immune and metabolic biomarkers for early detection of neonatal sepsis-protocol for a prospective multicohort study. BMJ Open 11(12), article number: e050100. (10.1136/bmjopen-2021-050100)
- Campion, S. L. et al. 2021. Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial. Journal of Clinical Investigation 131(23), article number: e150823. (10.1172/JCI150823)
- Clement, M. et al. 2021. CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor. Proceedings of the National Academy of Sciences 118(29), article number: e2019639118. (10.1073/pnas.2019639118)
2020
- Narayanan, G. A. et al. 2020. The MAIT TCRβ chain contributes to discrimination of microbial ligand. Immunology and Cell Biology 98(9), pp. 770-781. (10.1111/imcb.12370)
- Shepherd, F. R. and McLaren, J. E. 2020. T cell immunity to bacterial pathogens: mechanisms of immune control and bacterial evasion. International Journal of Molecular Sciences 21(17), article number: 6144. (10.3390/ijms21176144)
- Pearson, F. E. et al. 2020. Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells. Clinical and Translational Immunology 9 (10.1002/cti2.1141)
- Edwards, S. C. et al. 2020. A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans. Journal of Experimental Medicine 217(5), article number: e20190834. (10.1084/jem.20190834)
- Starke, C. E. et al. 2020. SIV-specific CD8+ T cells are clonotypically distinct across lymphoid and mucosal tissues. Journal of Clinical Investigation 130(2), pp. 789-798. (10.1172/JCI129161)
- Brenna, E. et al. 2020. CD4+ T follicular helper cells in human tonsils and blood are clonally convergent but divergent from Non-Tfh CD4+ cells. Cell Reports 30(1), pp. 137-152. (10.1016/j.celrep.2019.12.016)
2019
- Meckiff, B. J. et al. 2019. Primary EBV infection induces an acute wave of activated antigen-specific cytotoxic CD4+ T cells. Journal of Immunology 203(3), article number: ji1900377. (10.4049/jimmunol.1900377)
- Wong, E. B. et al. 2019. TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis. Communications Biology 2(1), pp. -., article number: 203. (10.1038/s42003-019-0442-2)
- Li, N. et al. 2019. Memory CD4+ T cells are generated in the human fetal intestine. Nature Immunology 20, pp. 301-312. (10.1038/s41590-018-0294-9)
- Mayassi, T. et al. 2019. Chronic inflammation permanently reshapes tissue-resident immunity in celiac disease. Cell 176(5), pp. 967-981.e19. (10.1016/j.cell.2018.12.039)
- McLaren, J. et al. 2019. IL-33 augments virus-specific memory T Cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccinea. Journal of Immunology 202(3), pp. 943-955. (10.4049/jimmunol.1701757)
2018
- Pogorelyy, M. V. et al. 2018. Exploring the pre-immune landscape of antigen-specific T cells. Genome Medicine 10, article number: 68. (10.1186/s13073-018-0577-7)
- Wun, K. S. et al. 2018. T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids. Nature Immunology 19, pp. 397-406. (10.1038/s41590-018-0065-7)
- Culina, S. et al. 2018. Islet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Science Immunology 3(20), article number: eaao4013. (10.1126/sciimmunol.aao4013)
- Shugay, M. et al. 2018. VDJdb: a curated database of T-cell receptor sequences with known antigen specificity. Nucleic Acids Research 46(D1), pp. D419-D427. (10.1093/nar/gkx760)
- Lissina, A. et al. 2018. Divergent roles for antigenic drive in the aetiology of primary versus dasatinib-associated CD8+ TCR-Vβ+ expansions. Scientific Reports 8(1), article number: 2534. (10.1038/s41598-017-18062-x)
2017
- Culshaw, A. et al. 2017. Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8+ T cell response. Nature Immunology 18, pp. 1228-1237. (10.1038/ni.3850)
- Davey, M. S. et al. 2017. Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance. Nature Communications 8, article number: 14760. (10.1038/ncomms14760)
- Dockree, T. et al. 2017. CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold. Immunology and Cell Biology 95(1), pp. 68-76. (10.1038/icb.2016.85)
2016
- Clement, M. et al. 2016. Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies. Scientific Reports 6, article number: 35332. (10.1038/srep35332)
- Pearson, J. A. et al. 2016. Proinsulin expression shapes the TCR repertoire but fails to control the development of low-avidity insulin-reactive CD8+ T cells. Diabetes 65(6), pp. 1679-1689. (10.2337/db15-1498)
2015
- Liuzzi, A. R., McLaren, J. E., Price, D. and Eberl, M. 2015. Early innate responses to pathogens: pattern recognition by unconventional human T-cells. Current Opinion in Immunology 36, pp. 31-37. (10.1016/j.coi.2015.06.002)
- Neller, M. A. et al. 2015. Naive CD8+ T-cell precursors display structured TCR repertoires and composite antigen-driven selection dynamics. Immunology and Cell Biology 93, pp. 625-633. (10.1038/icb.2015.17)
- Petersen, J. et al. 2015. Determinants of gliadin-specific T cell selection in celiac disease. The Journal of Immunology 194(12), pp. 6112-6122. (10.4049/jimmunol.1500161)
- Kloverpris, H. N. et al. 2015. CD8+ TCR bias and immunodominance in HIV-1 infection. The Journal of Immunology 194(11), pp. 5329-5345. (10.4049/jimmunol.1400854)
- Roberto, A. et al. 2015. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood 125(18), pp. 2855-2864. (10.1182/blood-2014-11-608406)
- Skowera, A. et al. 2015. β-Cell-specific CD8 T Cell phenotype in Type 1 diabetes reflects chronic autoantigen exposure. Diabetes 64(3), pp. 916-925. (10.2337/db14-0332)
- Costa, A. I. et al. 2015. Complex T-cell receptor repertoire dynamics underlie the CD8+T-cell response to HIV-1. Journal of Virology 89(1), pp. 110-119. (10.1128/JVI.01765-14)
2014
- Pearson, J., Thayer, T. C., McLaren, J. E., Miners, K. L., Ladell, K. I., Price, D. and Wong, F. S. 2014. Analysis of the repertoire of insulin-reactive CD8(+) T cells [Abstract]. Immunology 143(S2), pp. 152-152. (10.1111/imm.12406)
- Bengsch, B. et al. 2014. Identification of a TSCM phenotype HCV-specific CD8+T cell response with superior functionality in chronic HCV infection [Abstract]. Hepatology 60, pp. 1071A-1072A., article number: 1815.
- Kløverpris, H. N. et al. 2014. Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load. AIDS 28(14), pp. 2007-2021. (10.1097/QAD.0000000000000362)
- Gold, M. C. et al. 2014. MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. Journal of Experimental Medicine 211(8), pp. 1601-1610. (10.1084/jem.20140507)
- Davies, T. S., Li, N., McLaren, J., Hughes, T. R. and Ramji, D. P. 2014. Pro- therogenic actions of interferon-gamma on macrophages in atherosclerosis. Cardiology 128(S1), pp. 278-278. (10.1159/000365062)
- Lissina, A. et al. 2014. The link between CD8+ T-cell antigen-sensitivity and HIV-suppressive capacity depends on HLA restriction, target epitope and viral isolate. AIDS 28(4), pp. 477-486. (10.1097/QAD.0000000000000175)
2013
- Ladell, K. I. et al. 2013. A molecular basis for the control of preimmune escape variants by HIV-specific CD8+ T cells. Immunity 38(3), pp. 425-436. (10.1016/j.immuni.2012.11.021)
2012
- Humphreys, I. R. et al. 2012. Avidity of influenza-specific memory CD8+T-cell populations decays over time compromising antiviral immunity. European Journal of Immunology 42(12), pp. 3235-3242. (10.1002/eji.201242575)
- Doherty, T. M. et al. 2012. A T Cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS ONE 7(10), article number: e48322. (10.1371/journal.pone.0048322)
2011
- Sexton, K. J., Balharry, D. C., Brennan, P., McLaren, J. E., Brewis, I. A. and Berube, K. A. 2011. Proteomic profiling of human respiratory epithelia by iTRAQ reveals biomarkers of exposure and harm by tobacco smoke components. Biomarkers 16(7), pp. 567-576. (10.3109/1354750X.2011.608855)
- McLaren, J. E., Michael, D. R., Guschina, I., Harwood, J. L. and Ramji, D. P. 2011. Eicosapentaenoic acid and docosahexaenoic acid regulate modified LDL uptake and macropinocytosis in human macrophages. Lipids 46(11), pp. 1053-1061.
- McLaren, J. E., Michael, D. R., Ashlin, T. G. and Ramji, D. P. 2011. Cytokines, macrophage lipid metabolism and foam cells: implications for cardiovascular disease therapy. Progress in Lipid Research 50(4), pp. 331-347. (10.1016/j.plipres.2011.04.002)
2010
- Li, N., McLaren, J. E., Michael, D. R., Clement, M., Fielding, C. A. and Ramji, D. P. 2010. ERK is integral to the IFN-γ-mediated activation of STAT1, the expression of key genes implicated in atherosclerosis, and the uptake of modified lipoproteins by human macrophages. The Journal of Immunology 185(5), pp. 3041-3048. (10.4049/jimmunol.1000993)
- McLaren, J. E. et al. 2010. IL-33 reduces macrophage foam cell formation. The Journal of Immunology 185(2), pp. 1222-1229. (10.4049/jimmunol.1000520)
- McLaren, J. E. et al. 2010. The TNF-like protein 1A-death receptor 3 pathway promotes macrophage foam cell formation in vitro. Journal of Immunology 184(10), pp. 5827-5834. (10.4049/jimmunol.0903782)
2009
- McLaren, J. E., Zuo, J., Grimstead, J. W., Poghosyan, Z., Bell, A. I., Rowe, M. and Brennan, P. 2009. STAT1 contributes to the maintenance of the latency III viral programme observed in Epstein-Barr virus-transformed B cells and their recognition by CD8+ T cells. Journal of General Virology 90(9), pp. 2239-2250. (10.1099/vir.0.011627-0)
- McLaren, J. E. and Ramji, D. P. 2009. Interferon gamma: A master regulator of atherosclerosis. Cytokine & Growth Factor Reviews 20(2), pp. 125-135. (10.1016/j.cytogfr.2008.11.003)
2007
- McLaren, J. E., Rowe, M. and Brennan, P. 2007. Epstein-Barr virus induces a distinct form of DNA-bound STAT1 compared with that found in interferon-stimulated B lymphocytes. Journal of General Virology 88(7), pp. 1876-1886. (10.1099/vir.0.82741-0)
- McLaren, J. E. 2007. Regulation of the STAT1 by the Epstein-Barr virus.. PhD Thesis, Cardiff University.
2006
- White, P. C., Shore, A. M., Clement, M., McLaren, J. E., Soeiro, I., Lam, E. W. and Brennan, P. 2006. Regulation of cyclin D2 and the cyclin D2 promoter by protein kinase A and CREB in lymphocytes. Oncogene 25(15), pp. 2170-2180. (10.1038/sj.onc.1209255)
Erthyglau
- Davies, K. and McLaren, J. 2024. Destabilisation of T cell-dependent humoral immunity in sepsis. Clinical Science 138(1), pp. 65-85. (10.1042/CS20230517)
- Oruganti, S. et al. 2023. Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study. BMJ Open 13, article number: e067002. (10.1136/bmjopen-2022-067002)
- Shepherd, F. R. et al. 2023. The superantigens SpeC and TSST-1 specifically activate TRBV12-3/12-4+ memory T cells. Communications Biology 6, article number: 78. (10.1038/s42003-023-04420-1)
- Goncharov, M. et al. 2022. VDJdb in the pandemic era: a compendium of T cell receptors specific for SARS-CoV-2. Nature Methods 19(9), pp. 1017–1019. (10.1038/s41592-022-01578-0)
- Pymm, P. et al. 2022. Epitope length variants balance protective immune responses and viral escape in HIV-1 infection. Cell Reports 38(9), article number: 110449. (10.1016/j.celrep.2022.110449)
- Misheva, M. et al. 2022. Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation. Nature Communications 13(1), article number: 139. (10.1038/s41467-021-27766-8)
- Chakraborty, M. et al. 2021. nSeP: immune and metabolic biomarkers for early detection of neonatal sepsis-protocol for a prospective multicohort study. BMJ Open 11(12), article number: e050100. (10.1136/bmjopen-2021-050100)
- Campion, S. L. et al. 2021. Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial. Journal of Clinical Investigation 131(23), article number: e150823. (10.1172/JCI150823)
- Clement, M. et al. 2021. CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor. Proceedings of the National Academy of Sciences 118(29), article number: e2019639118. (10.1073/pnas.2019639118)
- Narayanan, G. A. et al. 2020. The MAIT TCRβ chain contributes to discrimination of microbial ligand. Immunology and Cell Biology 98(9), pp. 770-781. (10.1111/imcb.12370)
- Shepherd, F. R. and McLaren, J. E. 2020. T cell immunity to bacterial pathogens: mechanisms of immune control and bacterial evasion. International Journal of Molecular Sciences 21(17), article number: 6144. (10.3390/ijms21176144)
- Pearson, F. E. et al. 2020. Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells. Clinical and Translational Immunology 9 (10.1002/cti2.1141)
- Edwards, S. C. et al. 2020. A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans. Journal of Experimental Medicine 217(5), article number: e20190834. (10.1084/jem.20190834)
- Starke, C. E. et al. 2020. SIV-specific CD8+ T cells are clonotypically distinct across lymphoid and mucosal tissues. Journal of Clinical Investigation 130(2), pp. 789-798. (10.1172/JCI129161)
- Brenna, E. et al. 2020. CD4+ T follicular helper cells in human tonsils and blood are clonally convergent but divergent from Non-Tfh CD4+ cells. Cell Reports 30(1), pp. 137-152. (10.1016/j.celrep.2019.12.016)
- Meckiff, B. J. et al. 2019. Primary EBV infection induces an acute wave of activated antigen-specific cytotoxic CD4+ T cells. Journal of Immunology 203(3), article number: ji1900377. (10.4049/jimmunol.1900377)
- Wong, E. B. et al. 2019. TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis. Communications Biology 2(1), pp. -., article number: 203. (10.1038/s42003-019-0442-2)
- Li, N. et al. 2019. Memory CD4+ T cells are generated in the human fetal intestine. Nature Immunology 20, pp. 301-312. (10.1038/s41590-018-0294-9)
- Mayassi, T. et al. 2019. Chronic inflammation permanently reshapes tissue-resident immunity in celiac disease. Cell 176(5), pp. 967-981.e19. (10.1016/j.cell.2018.12.039)
- McLaren, J. et al. 2019. IL-33 augments virus-specific memory T Cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccinea. Journal of Immunology 202(3), pp. 943-955. (10.4049/jimmunol.1701757)
- Pogorelyy, M. V. et al. 2018. Exploring the pre-immune landscape of antigen-specific T cells. Genome Medicine 10, article number: 68. (10.1186/s13073-018-0577-7)
- Wun, K. S. et al. 2018. T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids. Nature Immunology 19, pp. 397-406. (10.1038/s41590-018-0065-7)
- Culina, S. et al. 2018. Islet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Science Immunology 3(20), article number: eaao4013. (10.1126/sciimmunol.aao4013)
- Shugay, M. et al. 2018. VDJdb: a curated database of T-cell receptor sequences with known antigen specificity. Nucleic Acids Research 46(D1), pp. D419-D427. (10.1093/nar/gkx760)
- Lissina, A. et al. 2018. Divergent roles for antigenic drive in the aetiology of primary versus dasatinib-associated CD8+ TCR-Vβ+ expansions. Scientific Reports 8(1), article number: 2534. (10.1038/s41598-017-18062-x)
- Culshaw, A. et al. 2017. Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8+ T cell response. Nature Immunology 18, pp. 1228-1237. (10.1038/ni.3850)
- Davey, M. S. et al. 2017. Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance. Nature Communications 8, article number: 14760. (10.1038/ncomms14760)
- Dockree, T. et al. 2017. CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold. Immunology and Cell Biology 95(1), pp. 68-76. (10.1038/icb.2016.85)
- Clement, M. et al. 2016. Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies. Scientific Reports 6, article number: 35332. (10.1038/srep35332)
- Pearson, J. A. et al. 2016. Proinsulin expression shapes the TCR repertoire but fails to control the development of low-avidity insulin-reactive CD8+ T cells. Diabetes 65(6), pp. 1679-1689. (10.2337/db15-1498)
- Liuzzi, A. R., McLaren, J. E., Price, D. and Eberl, M. 2015. Early innate responses to pathogens: pattern recognition by unconventional human T-cells. Current Opinion in Immunology 36, pp. 31-37. (10.1016/j.coi.2015.06.002)
- Neller, M. A. et al. 2015. Naive CD8+ T-cell precursors display structured TCR repertoires and composite antigen-driven selection dynamics. Immunology and Cell Biology 93, pp. 625-633. (10.1038/icb.2015.17)
- Petersen, J. et al. 2015. Determinants of gliadin-specific T cell selection in celiac disease. The Journal of Immunology 194(12), pp. 6112-6122. (10.4049/jimmunol.1500161)
- Kloverpris, H. N. et al. 2015. CD8+ TCR bias and immunodominance in HIV-1 infection. The Journal of Immunology 194(11), pp. 5329-5345. (10.4049/jimmunol.1400854)
- Roberto, A. et al. 2015. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood 125(18), pp. 2855-2864. (10.1182/blood-2014-11-608406)
- Skowera, A. et al. 2015. β-Cell-specific CD8 T Cell phenotype in Type 1 diabetes reflects chronic autoantigen exposure. Diabetes 64(3), pp. 916-925. (10.2337/db14-0332)
- Costa, A. I. et al. 2015. Complex T-cell receptor repertoire dynamics underlie the CD8+T-cell response to HIV-1. Journal of Virology 89(1), pp. 110-119. (10.1128/JVI.01765-14)
- Pearson, J., Thayer, T. C., McLaren, J. E., Miners, K. L., Ladell, K. I., Price, D. and Wong, F. S. 2014. Analysis of the repertoire of insulin-reactive CD8(+) T cells [Abstract]. Immunology 143(S2), pp. 152-152. (10.1111/imm.12406)
- Bengsch, B. et al. 2014. Identification of a TSCM phenotype HCV-specific CD8+T cell response with superior functionality in chronic HCV infection [Abstract]. Hepatology 60, pp. 1071A-1072A., article number: 1815.
- Kløverpris, H. N. et al. 2014. Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load. AIDS 28(14), pp. 2007-2021. (10.1097/QAD.0000000000000362)
- Gold, M. C. et al. 2014. MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. Journal of Experimental Medicine 211(8), pp. 1601-1610. (10.1084/jem.20140507)
- Davies, T. S., Li, N., McLaren, J., Hughes, T. R. and Ramji, D. P. 2014. Pro- therogenic actions of interferon-gamma on macrophages in atherosclerosis. Cardiology 128(S1), pp. 278-278. (10.1159/000365062)
- Lissina, A. et al. 2014. The link between CD8+ T-cell antigen-sensitivity and HIV-suppressive capacity depends on HLA restriction, target epitope and viral isolate. AIDS 28(4), pp. 477-486. (10.1097/QAD.0000000000000175)
- Ladell, K. I. et al. 2013. A molecular basis for the control of preimmune escape variants by HIV-specific CD8+ T cells. Immunity 38(3), pp. 425-436. (10.1016/j.immuni.2012.11.021)
- Humphreys, I. R. et al. 2012. Avidity of influenza-specific memory CD8+T-cell populations decays over time compromising antiviral immunity. European Journal of Immunology 42(12), pp. 3235-3242. (10.1002/eji.201242575)
- Doherty, T. M. et al. 2012. A T Cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS ONE 7(10), article number: e48322. (10.1371/journal.pone.0048322)
- Sexton, K. J., Balharry, D. C., Brennan, P., McLaren, J. E., Brewis, I. A. and Berube, K. A. 2011. Proteomic profiling of human respiratory epithelia by iTRAQ reveals biomarkers of exposure and harm by tobacco smoke components. Biomarkers 16(7), pp. 567-576. (10.3109/1354750X.2011.608855)
- McLaren, J. E., Michael, D. R., Guschina, I., Harwood, J. L. and Ramji, D. P. 2011. Eicosapentaenoic acid and docosahexaenoic acid regulate modified LDL uptake and macropinocytosis in human macrophages. Lipids 46(11), pp. 1053-1061.
- McLaren, J. E., Michael, D. R., Ashlin, T. G. and Ramji, D. P. 2011. Cytokines, macrophage lipid metabolism and foam cells: implications for cardiovascular disease therapy. Progress in Lipid Research 50(4), pp. 331-347. (10.1016/j.plipres.2011.04.002)
- Li, N., McLaren, J. E., Michael, D. R., Clement, M., Fielding, C. A. and Ramji, D. P. 2010. ERK is integral to the IFN-γ-mediated activation of STAT1, the expression of key genes implicated in atherosclerosis, and the uptake of modified lipoproteins by human macrophages. The Journal of Immunology 185(5), pp. 3041-3048. (10.4049/jimmunol.1000993)
- McLaren, J. E. et al. 2010. IL-33 reduces macrophage foam cell formation. The Journal of Immunology 185(2), pp. 1222-1229. (10.4049/jimmunol.1000520)
- McLaren, J. E. et al. 2010. The TNF-like protein 1A-death receptor 3 pathway promotes macrophage foam cell formation in vitro. Journal of Immunology 184(10), pp. 5827-5834. (10.4049/jimmunol.0903782)
- McLaren, J. E., Zuo, J., Grimstead, J. W., Poghosyan, Z., Bell, A. I., Rowe, M. and Brennan, P. 2009. STAT1 contributes to the maintenance of the latency III viral programme observed in Epstein-Barr virus-transformed B cells and their recognition by CD8+ T cells. Journal of General Virology 90(9), pp. 2239-2250. (10.1099/vir.0.011627-0)
- McLaren, J. E. and Ramji, D. P. 2009. Interferon gamma: A master regulator of atherosclerosis. Cytokine & Growth Factor Reviews 20(2), pp. 125-135. (10.1016/j.cytogfr.2008.11.003)
- McLaren, J. E., Rowe, M. and Brennan, P. 2007. Epstein-Barr virus induces a distinct form of DNA-bound STAT1 compared with that found in interferon-stimulated B lymphocytes. Journal of General Virology 88(7), pp. 1876-1886. (10.1099/vir.0.82741-0)
- White, P. C., Shore, A. M., Clement, M., McLaren, J. E., Soeiro, I., Lam, E. W. and Brennan, P. 2006. Regulation of cyclin D2 and the cyclin D2 promoter by protein kinase A and CREB in lymphocytes. Oncogene 25(15), pp. 2170-2180. (10.1038/sj.onc.1209255)
Gosodiad
- McLaren, J. E. 2007. Regulation of the STAT1 by the Epstein-Barr virus.. PhD Thesis, Cardiff University.
- Shepherd, F. R. et al. 2023. The superantigens SpeC and TSST-1 specifically activate TRBV12-3/12-4+ memory T cells. Communications Biology 6, article number: 78. (10.1038/s42003-023-04420-1)
Addysgu
Addysgu:
- MET921 - MSc Imiwnoleg Glinigol Gymhwysol ac Arbrofol
- Gradd MBBCh SSC Blwyddyn 2: Imiwnoleg Ryngweithiol a Chlefydau Heintus - Darlithydd a chyfrannwr ymarferol
- Gradd MBBCh SSC Blwyddyn 1: Adolygiad Llenyddiaeth
- Llwyfan gradd MBBCh Blwyddyn 1 ar gyfer Gwyddoniaeth Glinigol (PCS): Imiwnoleg Gymhwysol - Tiwtor Academaidd
- Tiwtor personol gradd MBBCh
Gwerthuso'r myfyrwyr:
- Arfarnwr Myfyrwyr PhD a Chadeirydd Panel
- PhD ac MSc arholwr myfyrwyr
Bywgraffiad
Dechreuodd fy ngyrfa ymchwil yn 2004 gyda Ph.D. yn labordy yr Athro Martin Rowe a Dr Paul Brennan ym Mhrifysgol Caerdydd. Yn ystod y cyfnod hwn, canolbwyntiodd fy ymchwil ar ddyrannu sut mae Firws Epstein-Barr (EBV) yn rheoleiddio mecanweithiau gwrthfeirysol allweddol (signalau interferon) yn ystod trawsnewidiad celloedd-B. Sbardunodd yr ymchwil hon fy niddordeb mewn modiwleiddio cytokine imiwnedd addasol. O'r fan hon, ymgymerais â'm swydd ôl-ddoethurol gyntaf, dan oruchwyliaeth Dr Dipak Ramji ym Mhrifysgol Caerdydd, lle astudiais sut y mae cytocinau yn trin ffurfio celloedd ewyn sy'n deillio o facroffagau. Mae ffurfio celloedd ewyn yn broses allweddol ym pathogenesis atherosclerosis a chlefyd y galon a phenderfynais y gallai interleukin-33 (IL-33) atal ffurfio celloedd ewyn macrophage, a oedd yn ddarganfyddiad newydd ar y pryd.
Yn 2010, dyfarnwyd Cymrodoriaeth Gwerth Ymddiriedolaeth Wellcome mewn Pobl (VIP) i ymuno â labordy yr Athro David Price ym Mhrifysgol Caerdydd i ehangu fy niddordebau mewn imiwnoleg firaol a bioleg cytokine. Yma, canolbwyntiais ar berfformio dulliau uwch-dechnoleg (cytometreg llif polychromatig, dilyniant derbynnydd celloedd T uwch) i ddeall sut mae ymatebion imiwn celloedd T sy'n benodol i antigen-benodol yn cael eu defnyddio mewn bodau dynol a llygod yn ystod firws (HIV, cytomegalofirws, EBV, firws dengue), coloneiddio microbaidd, llid a chlefyd. Yn ystod y gymrodoriaeth hon a thu hwnt (2010-2018), rwyf wedi gwneud rhai cyfraniadau sylweddol i'r maes imiwnolegol, gan gynnwys nifer o gyhoeddiadau effaith uchel (Cell, Imiwnoleg Natur, Imiwnoleg Gwyddoniaeth, Imiwnedd, Journal of Experimental Medicine), ac rwyf wedi cael gwahoddiad i roi darlithoedd ar yr ymchwil hon mewn cynadleddau, cwmnïau biotechnoleg a sefydliadau academaidd yn y DU ac Awstralia. Yn ogystal, ehangais fy niddordebau mewn cytocinau (ee IL-33) trwy archwilio sut maent yn rheoleiddio imiwnedd celloedd T yn ystod haint firws yn vivo.
Yn 2018, cefais fy recriwtio fel Darlithydd mewn Imiwnedd Systemau ym Mhrifysgol Caerdydd i gymhwyso fy arbenigedd mewn proffilio celloedd T yn ystod yr haint ar gyfer "Project Sepsis", cydweithrediad ymchwil newydd a sefydlwyd i fynd i'r afael ag angen meddygol brys i roi diagnosis cywir o sepsis ac i ddatblygu ymyriadau therapiwtig newydd. Yn 2023, cefais fy nyrchafu i Uwch-ddarlithydd ac mae fy niddordebau ymchwil ar hyn o bryd yn canolbwyntio ar ddeall sut mae celloedd T yn ymateb i heintiau bacteriol a firaol a hefyd sut mae'r organebau mircro-organebau hyn yn defnyddio strategaethau i osgoi celloedd T
Anrhydeddau a dyfarniadau
- Grant Cronfa Deithio Rutherford Prifysgol Caerdydd (2018)
- Gwobr Teithio Cymdeithas Imiwnoleg Prydain – 41ain Gweithfan Rhyngwladol Rhyngwladol Herpesvirus, Madison, WI, UDA (2016)
- Gwobr Cronfa Morgan E Williams Prifysgol Caerdydd (2016)
- Gwobr Cronfa WM Thomas Prifysgol Caerdydd (2016)
- Gwobr 1af am y cyflwyniad gorau yng nghyfarfod blynyddol I3-IRG Prifysgol Caerdydd (2007)
- Cymrodoriaeth Teithio - 12fed cynhadledd ddwyflynyddol y Gymdeithas Ryngwladol ar gyfer Ymchwil ar Firws Epstein-Barr a Chlefydau Cysylltiedig, Boston, MA, UDA (2006)
Aelodaethau proffesiynol
- Aelod o Gymdeithas Imiwnoleg Prydain
Safleoedd academaidd blaenorol
- 2023-presennol: Uwch Ddarlithydd mewn Imiwnoleg, Is-adran Heintiau ac Imiwnedd, Prifysgol Caerdydd, y DU
- 2018-2023: Darlithydd mewn Imiwnedd Systemau, Is-adran Heintiau ac Imiwnedd, Prifysgol Caerdydd, UK
- 2011-2018: Cydymaith Ymchwil, Is-adran Heintiau ac Imiwnedd, Prifysgol Caerdydd, y DU
- 2014: Ysgolhaig Ymweld, Canolfan Ymchwil Brechlynnau, NIAID, NIH, Bethesda, MD 20982, UDA
- 2010-2011: Cymrawd Ymchwil Gwerth mewn Pobl Ymddiriedolaeth Wellcome, Prifysgol Caerdydd, UK
- 2007-2010: British Heart Foundation Research Associate, Ysgol y Biowyddorau, Prifysgol Caerdydd, UK
Pwyllgorau ac adolygu
Pwyllgorau ac adolygu grant:
- Adolygydd grant, Cyngor Ymchwil Meddygol
- Adolygydd grant, Academi Gwyddorau Meddygol
- Adolygydd y grant, Agence Nationale de la Recherche (Ffrainc)
- Adolygydd grant, Sefydliad Gwyddoniaeth Cenedlaethol y Swistir
- Panel grant, Ymddiriedolaeth Wellcome/ISSF Prifysgol Caerdydd
- Adolygydd / panel grant, Cyfrif Cyflymu Effaith Cysoni UKRI
- Panel Arbenigol ECR. Oxford Open Immunology
Adolygiad cyfnodolyn:
- Adolygydd cyfnodolyn, Advanced Science
- Journal Reviewer, European Journal of Immunology
- Adolygydd cyfnodolyn, Frontiers in Immunology
- Adolygydd cyfnodolyn, Frontiers in Virology
- Adolygydd Cyfnodolion, iScience
- Journal Reviewer, International Journal of Molecular Sciences
- Journal Reviewer, Journal of Immunology
- Adolygydd cyfnodolyn, Lancet EBioMedicine
- Adolygydd Cyfnodolion, Cyfathrebu Natur
Bwrdd golygyddol:
- Adran Olygydd, Journal of Immunology
- Bwrdd golygyddol, Frontiers in Genetics
- Bwrdd golygyddol, Frontiers in Medicine
Meysydd goruchwyliaeth
Mae gen i ddiddordeb mewn goruchwylio myfyrwyr PhD sydd â diddordeb cryf mewn imiwnoleg celloedd T ym meysydd:
- Imiwnedd celloedd T sy'n benodol i firws
- Imiwnedd celloedd T sy'n cael ei yrru gan facteria
- modulation sy'n cael ei yrru gan cytokine imiwnedd addasol
- Mecanweithiau atal imiwnedd yn ystod sepsis
Goruchwyliaeth gyfredol
Kate Davies
Myfyriwr ymchwil
Prosiectau'r gorffennol
- Katherine Stanswood (2022) - MSc Imiwnoleg Glinigol Gymhwysol ac Arbrofol (prosiect traethawd hir) - "Mecanweithiau imiwnoteipio camweithrediad celloedd T yn ystod dyfodiad sepsis"
- Annie Bird (2022) - MSc Biowybodeg (prosiect traethawd hir) - "Chwyldroi ffenoteipio cellog: Proffilio trawsgrifiad a phroteipio protein gan ddefnyddio dilyniannu aml-omeg un gell"
- Lucy Sheikh (2023) - Prosiect traethawd hir MSc Imiwnoleg Glinigol Gymhwysol ac Arbrofol - "imiwnedd celloedd T gwrthficrobaidd camweithredol imiwnoteipio yn ystod sepsis"
Ymgysylltu
- Cyfrannwr gweithredol at Wyddoniaeth mewn Iechyd Prifysgol Caerdydd: Wythnos fyw
- Cyfrannwr at Brosiect Allgymorth Rhwydwaith Cymdeithas Ddysgedig Cymru a Seren 2018
Themâu ymchwil
Arbenigeddau
- Imiwnoleg
- Imiwnoleg cellog
- Afiechydon heintus
- Imiwnedd celloedd T