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Research
Immune regulation, autoimmune disease and infection
Studying immune regulation and autoimmune disease in patient cohorts and model systems, focusing on the biology of clinical outcome.
The Smith laboratory studies immunological mechanisms underlying immune-mediated disease and immunodeficiency in humans. The lab runs a translational program in autoimmune disease (particularly SLE, vasculitis and IBD) that has led to the discovery of a prognosis-predicting biomarker entering clinical trials, and to the identification of new pathways driving disease outcomes in autoimmunity and infection. It leads the NIHR BioResource Rare Diseases Primary immunodeficiency programme. By integrating genetics with human and animal studies and using advanced bioinformatic methodology, the laboratory tries to explore fundamental immunological mechanisms that are relevant to human disease, and to translate these results into applications of direct benefit to patients. During the pandemic the lab has led a programme focussed on immune responses to SARS-CoV-2.
Top 10 SELECTED PAPERS since 2000
- Thaventhiran, J.E.D., Lango Allen, H., Burren O.S., et al., and Smith, K.G.C., “Genetics of primary immunodeficiency revealed by genome sequencing a sporadic cohort.” Nature, 2020;583:90-95. doi:10.1038/s41586-020-2265-1.
- Lyons, P.A., Peters, J.E., Alberici, .F., et al., and Smith, K.G.C. "Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status." Nature Communications, 2019;5120. doi:10.1038/s41467-019-12515-9.
- Bashford-Rogers, R.J.M., Bergamaschi, L., McKinney, E.F., Pombal, D.C., Mescia, F., Lee, J.C., Thomas, D.C., Flint, S.M., Kellam, P., Jayne, D.R.W., Lyons, P.A., and Smith, K.G.C. "Analysis of the B cell receptor repertoire in six immune-mediated diseases" Nature, 2019;574:122-126. doi:10.1038/s41586-019-1595-3.
- Lee, J.C., Biasci, D., Roberts, R., Gearry, R.B., Mansfield, J.C., Ahmad, T., Prescott, N.J., Satsangi, J., Wilson, D.C., Jostins, L., Anderson, C.A., Consortium, U.I.G., Traherne, J.A., Lyons, P.A., Parkes, M. and Smith, K.G.C. "Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease." Nature Genetics, 2017;49:262-268. doi:10.1038/ng.3755.
- Thomas, D.C., Clare, S., Sowerby, J.M., Pardo, M., Juss, J.K., Goulding, D.A., van der Weyden, L., Storisteanu, D., Prakash, A., Espeli, M., Flint, S., Lee, J.C., Hoenderdos, K., Kane, L., Harcourt, K., Mukhopadhyay, S., Umrania, Y., Antrobus, R., Nathan, J.A., Adams, D.J., Bateman. A., Choudhary, J.S., Lyons, P.A., Condliffe, A.M., Chilvers, E.R., Dougan, G. and Smith, K.G.C. "Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity." Journal of Experimental Medicine, 2017;214:1111-1128. doi:10.1084/jem.20161382.
- McKinney, E.F., Lee, J.C., Jayne, D.R., Lyons, P.A. and Smith, K.G.C. "T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection." Nature, 2015;523:612-616. doi:10.1038/nature14468.
- Lee, J.C., Espeli, M., Anderson, C.A., et al., and Smith, K.G.C. "Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway." Cell, 2013;155:57-69. doi:10.1016/j.cell.2013.08.034.
- Lyons, P.A., Rayner, T.F., Trivedi, et al., and Smith, K.G.C. "Genetically distinct subsets within ANCA-associated vasculitis." New England Journal of Medicine, 2012;367:214-223. doi:10.1056/NEJMoa1108735.
- , Divekar, D.P., Beaton, L., Hogan, J.J., Fagarasan, S., Liston, A., Smith, K.G.C.* and Vinuesa, C.G.* (equal senior authors). "Foxp3+ follicular regulatory T cells control the germinal center response." Nature Medicine, 2011;17:975-982. doi:10.1038/nm.2425.
- McKinney, E.F., Lyons, P.A., Carr, E.J., Hollis, J.L., Jayne, D.R., Willcocks, L.C., Koukoulaki, M., Brazma, A., Jovanovic, V., Kemeny, D.M., Pollard, A.J., Macary, P.A., Chaudhry, A.N. and Smith, K.G.C. "A CD8+ T cell transcription signature predicts prognosis in autoimmune disease." Nature Medicine, 2010;16:586-591. doi:10.1038/nm.2130.