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.

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1. McKinney EF, Lee JC, Jayne DR, Lyons PA and Smith KGC. “T-cell exhaustion, costimulation and clinical outcome in autoimmunity and infection.” Nature, 2015; 523: 612- 616; PMC4623162.
2. Biasci D, Lee JC, Noor NM, Pombal DR, Hou M, Lewis N, Ahmad T, Hart A, Parkes M, McKinney EF, Lyons PA, and Smith KGC. “A blood-based prognostic biomarker in inflammatory bowel disease.”  Gut, 2019; 10.1136/gutjnl-2019-318343.
3. McKinney EF, Lyons PA, Carr EJ, Hollis JL, Jayne DRW, Willcocks LC, Koukoulaki M, Hatton A, MacAry PA, et al. and Smith KGC. “A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.” Nature Medicine, 2010; 16:586-589; PMC3504359.
4. Lee JC, Lyons PA, McKinney EF, Sowerby JM, Carr EJ, Bredin F, Rickman HM, Ratlamwala H, Hatton A, et al. and Smith KGC. “Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis.” Journal of Clinical Investigation, 2011; 121:4170-4179; PMC3196314.
5. Lee JC, Espéli M, Anderson CA, Linterman MA, Pocock JM, Williams NJ, Roberts R, Viatte S, Fu B, Peschu N, et al, and Smith KGC. “Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway.” Cell, 2013; 155: 57-69; PMC3790457.
6. Lee JC, Biasci D, Roberts R, Gearry RB, Mansfield JC, Ahmad T, Prescott NJ, Satsangi J, Wilson DC, Jostins L, Anderson CA, Consortium UIG, Traherne JA, Lyons PA, Parkes M and Smith KGC. "Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease." Nature Genetics, 2017; 49:262268; PMC5730041.
7. Peters JE, Lyons PA, Lee JC, Richard AC, Fortune MD, Newcombe PJ, Richardson S and Smith KGC. "Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease." PLoS Genetics, 2016; 12:e1005908
8. Richard AC, Peters JE, Lee JC, Vahedi G, Schaffer AA, Siegel RM, Lyons PA and Smith KGC. "Targeted genomic analysis reveals widespread autoimmune disease association with regulatory variants in the TNF superfamily cytokine signalling network." Genome Medicine, 2016; 8:76
9. Richard AC, Peters JE, Savinykh N, Lee JC, Hawley ET, Meylan F, Siegel RM, Lyons PA and Smith KGC. "Reduced monocyte and macrophage TNFSF15/TL1A expression is associated with susceptibility to inflammatory bowel disease". PLoS Genetics, 2018; 14.9:e1007458
10. Lyons PA, Peters JE, Alberici F, Liley J, et al. Wallace C and Smith KGC. “Genetically distinct clinical subsets, and associations with asthma and eosinophil abundance, within Eosinophilic Granulomatosis with Polyangiitis.” Nature Communications 2019; in press and BioRxiv doi: https://doi.org/10.1101/491837.
11. Bashford-Rogers RJM, Bergamaschi L, McKinney EF, Pombal DC, Mescia F, Lee JC, Thomas DC, Flint SM, Kellam P, Jayne DRW, Lyons PA and Smith KGC. “B cell receptor repertoire analysis in six immune-mediated diseases”. Nature 2019; under revision
12. Espéli M, Bashford-Rogers RJM, Sowerby JM, Alouche N, Wong L, Denton AE, Linterman MA and Smith KGC. “FcgRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human.” Nature Communications, 2019;10:1970; PMC6488660.
13. Thaventhiran JED, Allen HL, Burren OS, et al., Ouwehand WL, Thrasher AJ and Smith KGC. “Whole Genome Sequencing of Primary Immunodeficiency reveals a role for common and rare variants in coding and non-coding sequences.” Nature 2019;under revision and BioRxiv doi: https://doi.org/10.1101/499988.

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