Professor Eoin McKinney is the Versus Arthritis Chair of Rheumatology in the Department of Medicine at the University of Cambridge, an honorary consultant in nephrology and transplantation at Cambridge University Hospitals NHS Foundation Trust and a faculty member of the Cambridge Centre for Artificial Intelligence in Medicine.
His laboratory research explores ‘systems immunology’, studying the interface between immune responses to infection and those driving inflammatory pathology by applying machine learning methods to the integration of multi-omics data. He also explores the building of interpretable predictive models for rapid translation into clinical practice while informing underlying disease biology and identifying novel therapeutic strategies for inflammatory diseases.
Biography
Eoin McKinney is a nephrologist with an interest in the pathways driving and marking severe, relapsing autoimmune disease. He holds a Wellcome Trust Fellowship, and his work explores parallel ways in which the immune response deals with persistent infection and persistent self-antigen during a number of relapsing autoimmune and inflammatory diseases.
The immune response is a powerful and complex system that has evolved to protect us from pathogens and from tumours. Losing control of that system results in immunopathology, manifest in a broad range of diseases including autoimmunity (such as T1D, lupus, multiple sclerosis), autoinflammatory disease (such as Crohn’s disease, Ulcerative colitis), infection and malignancy.
Research
The McKinney Group use a systems immunology approach – modelling a broad range of quantitative traits as a means of discovering previously unsuspected relationships between them – to better understand the dysfunctional immune response in human disease. Our goal is to better understand what shapes that aberrant response and to use that information to indicate novel tests and/or interventions that can help clinicians treating immune pathology.
Using a custom spotted oligo microarray platform to investigate gene expression signatures in autoimmune diseases, specifically ANCA-associated systemic vasculitis and SLE. The highly heterogeneous clinical phenotypes seen in these syndromes make classification and diagnosis problematic and potentially confound attempts to further investigate underlying pathogenesis.
A cell separation step in RNA extraction from whole blood to derive labelled cDNA from 5 cell subsets (CD4,8,14,16 and 19) as well as unseparated PBMC. Samples are collected during active disease and subsequently after 3 and 12 months of therapy, during which time patients undergo close clinical monitoring. This allows correlation of derived expression signatures with extensive clinical data and mining for novel disease biomarkers with both diagnostic and prognostic value.
Publications
Profile on ORCID Connecting research and researchers
- Bashford-Rogers RJM, Bergamaschi L, McKinney EF, Pombal DC, Mescia F, Lee JC, Thomas DC, Flint SM, Kellam P, Jayne DRW, Lyons PA, Smith KGC. 2019. Analysis of the B cell receptor repertoire in six immune-mediated diseases. Nature, 2019 in press.
- Biasci D, Lee JC, Noor NM, Pombal DR, Hou M, Lewis N, Ahmad T, Hart A, Parkes M, McKinney EF, Lyons PA, Smith KGC. 2019. A blood-based prognostic biomarker in IBD. Gut 68: 1386-95
- Hulsen T, Jamuar SS, Moody AR, Karnes JH, Varga O, Hedensted S, Spreafico R, Hafler DA, McKinney EF. 2019. From Big Data to Precision Medicine. Front Med (Lausanne) 6: 34
- McKinney EF, Smith KGC. 2018. Metabolic exhaustion in infection, cancer and autoimmunity. Nat Immunol
- McKinney EF & Smith KGC. T cell exhaustion and immune-mediated disease – the potential for therapeutic exhaustion. Current Opinion in Immunology 2016. DOI: 10.1016/j.coi.2016.09.005
- McKinney EF & Smith KGC. Metabolic exhaustion in cancer, infection and autoimmunity. Nature Immunology 2018. DOI: 10.1038/s41590-018-0045-y
- McKinney EF, Smith KG. 2016. T-cell exhaustion: understanding the interface of chronic viral and autoinflammatory diseases. Immunol Cell Biol 94: 935-42
- Flint SM, Jovanovic V, Teo BW, Mak A, Thumboo J, McKinney EF, Lee JC, MacAry P, Kemeny DM, Jayne DR, Fong KY, Lyons PA, Smith KG. 2016. Leucocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases. RMD Open 2: e000183
- McKinney EF, Lee JC, Jayne DRW, Lyons PA, Smith KGC. 2015. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature 523: 612-6
- Flint SM, McKinney EF, Lyons PA, Smith KG. 2015. The Contribution of Transcriptomics to Biomarker Development in Systemic Vasculitis and SLE. Curr Pharm Des 21: 2225-35
- Flint SM, McKinney EF, Smith KG. 2015. Emerging concepts in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis. Curr Opin Rheumatol 27: 197-203
- McKinney EF, Willcocks LC, Broecker V, Smith KG. 2014. The immunopathology of ANCA-associated vasculitis. Semin Immunopathol 36: 461-78
- Richard AC, Lyons PA, Peters JE, Biasci D, Flint SM, Lee JC, McKinney EF, Siegel RM, Smith KG. 2014. Comparison of gene expression microarray data with count-based RNA measurements informs microarray interpretation. BMC Genomics 15: 649
- Toshner M, Dunmore BJ, McKinney EF, Southwood M, Caruso P, Upton PD, Waters JP, Ormiston ML, Skepper JN, Nash G, Rana AA, Morrell NW. 2014. Transcript analysis reveals a specific HOX signature associated with positional identity of human endothelial cells. PLoS One 9: e91334
- Ferreira RC, Guo H, Coulson RM, Smyth DJ, Pekalski ML, Burren OS, Cutler AJ, Doecke JD, Flint S, McKinney EF, Lyons PA, Smith KG, Achenbach P, Beyerlein A, Dunger DB, Clayton DG, Wicker LS, Todd JA, Bonifacio E, Wallace C, Ziegler AG. 2014. A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes. Diabetes 63: 2538-50
- Ahmed ST, Akirav E, Bradshaw E, Buckner J, McKinney E, Quintana FJ, Waldron-Lynch F, Nepom J. 2013. Immunological biomarkers: catalysts for translational advances in autoimmune diabetes. Clin Exp Immunol 172: 178-85
- Jovanovic V, Abdul Aziz N, Lim YT, Ng Ai Poh A, Jin Hui Chan S, Ho Xin Pei E, Lew FC, Shui G, Jenner AM, Bowen L, McKinney EF, Lyons PA, Kemeny MD, Smith KG, Wenk MR, Macary PA. 2013. Lipid anti-lipid antibody responses correlate with disease activity in systemic lupus erythematosus. PLoS One 8: e55639
- Kain R, Tadema H, McKinney EF, Benharkou A, Brandes R, Peschel A, Hubert V, Feenstra T, Sengolge G, Stegeman C, Heeringa P, Lyons PA, Smith KG, Kallenberg C, Rees AJ. 2012. High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis. J Am Soc Nephrol 23: 556-66
- Lee JC, Lyons PA, McKinney EF, Sowerby JM, Carr EJ, Bredin F, Rickman HM, Ratlamwala H, Hatton A, Rayner TF, Parkes M, Smith KG. 2011. Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis. J Clin Invest 121: 4170-9
- McKinney EF, Lyons PA, Carr EJ, Hollis JL, Jayne DR, Willcocks LC, Koukoulaki M, Brazma A, Jovanovic V, Kemeny DM, Pollard AJ, Macary PA, Chaudhry AN, Smith KG. 2010. A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. Nat Med 16: 586-91
- Lyons PA ME, Rayner TF, Hatton A, Woffendin HB, Koukoulaki M, Freeman TC, Jayne DR, Chaudhry AN, Smith KGC. 2009. Novel expression signatures identified by transcriptional analysis of separated leukocyte subsets in SLE and vasculitis. Ann Rheum Dis Epub ahead of print
- Arnott ID, Nimmo ER, Drummond HE, Fennell J, Smith BR, MacKinlay E, Morecroft J, Anderson N, Kelleher D, O'Sullivan M, McManus R, Satsangi J. 2004. NOD2/CARD15, TLR4 and CD14 mutations in Scottish and Irish Crohn's disease patients: evidence for genetic heterogeneity within Europe? Genes Immun 5: 417-25
- Newport MJ, Allen A, Awomoyi AA, Dunstan SJ, McKinney E, Marchant A, Sirugo G. 2004. The toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia. Tuberculosis (Edinb) 84: 347-52
- Mattsson C, Lai M, Noble J, McKinney E, Yau JL, Seckl JR, Walker BR. 2003. Obese Zucker rats have reduced mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 1 expression in hippocampus-implications for dysregulation of the hypothalamic-pituitary-adrenal axis in obesity. Endocrinology 144: 2997-3003
- Marshall SE, McLaren AJ, McKinney EF, Bird TG, Haldar NA, Bunce M, Morris PJ, Welsh KI. 2001. Donor cytokine genotype influences the development of acute rejection after renal transplantation. Transplantation 71: 469-76
- McKinney EF, Walton RT, Yudkin P, Fuller A, Haldar NA, Mant D, Murphy M, Welsh KI, Marshall SE. 2000. Association between polymorphisms in dopamine metabolic enzymes and tobacco consumption in smokers. Pharmacogenetics 10: 483-91