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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 combines genetics, genomics, immunology and clinical medicine, integrating detailed laboratory analysis of mechanisms of immune regulation with a prospective translational medicine programme in major autoimmune and inflammatory diseases.
The main focus of the group is investigation of the biology underlying clinical outcome in immune-mediated disease. Western medicine has focused on categorising disease into defined diagnostic categories, but what determines patient outcome is the long-term course the disease takes following diagnosis.
Significant Publications
Thomas DC, Clare S, Sowerby JM, Pardo M, Juss JK, Goulding DA, van der Weyden L, Storisteanu D, Prakash A, Espéli M, Flint S, Lee JC, Hoenderdos K, Kane L, Harcourt K, Mukhopadhyay S, Umrania Y, Antrobus R, Nathan JA, Adams DJ, Bateman A, Choudhary JS, Lyons PA, Condliffe AM, Chilvers ER, Dougan G and Smith KGC (2017). “Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity.” J Exp Med. 214(4):1111-1128. doi: 10.1084/jem.20161382
Lee JC, Biasci D, Roberts R, Gearry RB, Mansfield JC, Ahmad T, Prescott NJ, Satsangi J, Wilson DC, Jostins L, Anderson CA; UK IBD Genetics Consortium., Traherne JA, Lyons PA, Parkes M and Smith KGC (2017). “Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease.” Nat Genet. 49(2):262-268. doi: 10.1038/ng.3755
Peters JE, Lyons PA, Lee JC, Richard AC, Fortune MD, Newcombe PJ, Richardson S and Smith KGC (2016). “Insight into genotype-phenotype associations through eQTL mapping in multiple cell types in health and immune-mediated disease.” PLoS Genet. 12(3):e1005908. doi: 10.1371/journal.pgen.1005908
McKinney EF, Lee, JC, Jayne DRW, Lyons PA and Smith KGC (2015). T cell exhaustion, costimulation and clinical outcome in autoimmunity and infection. Nature 523(7562): 612-616. doi: 10.1038/nature14468.
Linterman, MA, Denton, AE, Divekar, DP, Zvetkova, I, Kane, L, Ferreira, C, Veldhoen, M, Clare, S, Dougan G, Espéli, M, and Smith, KGC (2014). CD28 expression is required after T cell priming for helper T cell responses and protective immunity to infection. ELIFE, 3. doi:10.7554/eLife.03180
Lee, J. C., M. Espeli, C. A. Anderson, M. A. Linterman, J. M. Pocock, N. J. Williams, R. Roberts, S. Viatte, B. Fu, N. Peshu, T. T. Hien, N. H. Phu, E. Wesley, C. Edwards, T. Ahmad, J. C. Mansfield, R. Gearry, S. Dunstan, T. N. Williams, A. Barton, C. G. Vinuesa, U. I. G. Consortium, M. Parkes, P. A. Lyons and K. G. Smith (2013). "Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway." Cell 155(1): 57-69.
Espeli, M., M. R. Clatworthy, S. Bokers, K. E. Lawlor, A. J. Cutler, F. Kontgen, P. A. Lyons and K. G. Smith (2012). "Analysis of a wild mouse promoter variant reveals a novel role for FcgammaRIIb in the control of the germinal center and autoimmunity." J Exp Med 209(12): 2307-2319.
Lyons, P. A., T. F. Rayner, S. Trivedi, J. U. Holle, R. A. Watts, D. R. Jayne, B. Baslund, P. Brenchley, A. Bruchfeld, A. N. Chaudhry, J. W. Cohen Tervaert, P. Deloukas, C. Feighery, W. L. Gross, L. Guillevin, I. Gunnarsson, L. Harper, Z. Hruskova, M. A. Little, D. Martorana, T. Neumann, S. Ohlsson, S. Padmanabhan, C. D. Pusey, A. D. Salama, J. S. Sanders, C. O. Savage, M. Segelmark, C. A. Stegeman, V. Tesar, A. Vaglio, S. Wieczorek, B. Wilde, J. Zwerina, A. J. Rees, D. G. Clayton and K. G. Smith (2012). "Genetically distinct subsets within ANCA-associated vasculitis." N Engl J Med 367(3): 214-223.
Lee, J. C., P. A. Lyons, E. F. McKinney, J. M. Sowerby, E. J. Carr, F. Bredin, H. M. Rickman, H. Ratlamwala, A. Hatton, T. F. Rayner, M. Parkes and K. G. Smith (2011). "Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis." J Clin Invest 121(10): 4170-4179.
Linterman, M. A., W. Pierson, S. K. Lee, A. Kallies, S. Kawamoto, T. F. Rayner, M. Srivastava, D. P. Divekar, L. Beaton, J. J. Hogan, S. Fagarasan, A. Liston, K. G. Smith and C. G. Vinuesa (2011). "Foxp3+ follicular regulatory T cells control the germinal center response." Nat Med 17(8): 975-982.
McKinney, E. F., P. A. Lyons, E. J. Carr, J. L. Hollis, D. R. Jayne, L. C. Willcocks, M. Koukoulaki, A. Brazma, V. Jovanovic, D. M. Kemeny, A. J. Pollard, P. A. Macary, A. N. Chaudhry and K. G. Smith (2010). "A CD8+ T cell transcription signature predicts prognosis in autoimmune disease." Nat Med 16(5): 586-591, 581p following 591.
Xiang, Z., A. J. Cutler, R. J. Brownlie, K. Fairfax, K. E. Lawlor, E. Severinson, E. U. Walker, R. A. Manz, D. M. Tarlinton and K. G. Smith (2007). "FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis." Nat Immunol 8(4): 419-429.
Floto, R. A., M. R. Clatworthy, K. R. Heilbronn, D. R. Rosner, P. A. MacAry, A. Rankin, P. J. Lehner, W. H. Ouwehand, J. M. Allen, N. A. Watkins and K. G. Smith (2005). "Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts." Nat Med 11(10): 1056-1058.