Research
I have been 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.
I am using 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
https://orcid.org/0000-0003-3516-3072
https://scholar.google.com/citations?view_op=list_works&hl=en&user=Dxn0a...
1. 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.
2. 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
3. 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
4. McKinney EF, Smith KGC. 2018. Metabolic exhaustion in infection, cancer and autoimmunity. Nat Immunol
5. McKinney EF, Smith KG. 2016. T cell exhaustion and immune-mediated disease-the potential for therapeutic exhaustion. Curr Opin Immunol 43: 74-80
6. McKinney EF, Smith KG. 2016. T-cell exhaustion: understanding the interface of chronic viral and autoinflammatory diseases. Immunol Cell Biol 94: 935-42
7. 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
8. 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
9. 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
10. Flint SM, McKinney EF, Smith KG. 2015. Emerging concepts in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis. Curr Opin Rheumatol 27: 197-203
11. McKinney EF, Willcocks LC, Broecker V, Smith KG. 2014. The immunopathology of ANCA-associated vasculitis. Semin Immunopathol 36: 461-78
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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
25. 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
