Professor Smith’s group works on immune regulation and autoimmune and inflammatory disease. This has focused on how naturally occurring variants in immune molecules such as FcγRIIB alter immune function and predispose to autoimmunity. The accumulation of these risk variants in the population has been shown to be, at least in part, due to their ability to protect against infections such as malaria. With Dr Lyons and in collaboration with Addenbrooke’s Vasculitis & SLE Clinic and the Division of Gastroenterology, Smith runs a translational programme studying the pathogenesis of human disease at the same time as looking for biomarkers. A CD8T cell transcriptional signature has been found which predicts prognosis in autoimmune disease. The European Vasculitis Genetics Consortium is also led from the laboratory.
Dr Clatworthy’s group is based within the Department of Medicine facility in the new LMB. We are interested in understanding how IgG antibodies and their receptors contribute to disease pathogenesis in autoimmunity, and to pathogen-associated and sterile inflammation, particularly in acute kidney injury. Dr Clatworthy has also established a two-photon imaging facility, and is using this technology to investigate how IgG can impact on the dynamic behaviour of leucocytes. Clatworthy’s clinical interests are in antibody-mediated rejection and B cell modulation in renal transplantation.
Professor Patrick Maxwell’s group is based in CIMR and works on genetic renal diseases and cellular oxygen sensing. He is supported by a Wellcome Trust Senior Investigator Award and is also Head of the School of Clinical Medicine.
Dr Bradley’s group has been studying the pathways involved in signaling by TNF-alpha family members in endothelial cells and their relevance to renal inflammation and transplant rejection. He coordinates the Yale-Cambridge Research Initiative, and is the Director of the NIHR Cambridge Biomedical Research Centre.
Professor Ashcroft's group is based in the Clifford Allbutt Building, and primarily focuses on elucidating the key regulatory mechanisms involved in hypoxia signalling in mammalian cells. The Ashcroft group has a strong interest in the hypoxia inducible factor (HIF) family of transcription factors and understanding their role in cancer, renal disease and other diseases. In particular, the Ashcroft group has been elucidating the role of mitochondria in oxygen sensing. In addition, Prof Ashcroft takes multidisciplinary collaborative approaches for leading the therapeutic development of novel small molecule hypoxia signalling targeting agents.
McKinney EF, Lee JC, Jayne DR, Lyons PA, Smith KGC. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature. 2015 Jul 30;523(7562):612-6. doi: 10.1038/nature14468.
Al-Lamki RS, Lu W, Wang J, Yang J, Sargeant TJ, Wells R, Suo C, Wright P, Goddard M, Huang Q, Lebastchi AH, Tellides G, Huang Y, Min W, Pober JS, Bradley JR. TNF, acting through inducibly expressed TNFR2, drives activation and cell cycle entry of c-Kit+ cardiac stem cells in ischemic heart disease. Stem Cells. 2013 Sep;31(9):1881-92.
Lyons PA, Rayner TF, Trivedi S, Holle JU, Watts RA, Jayne DRW, Baslund B, Brenchley P, Bruchfeld A, Chaudhry AN, Cohen Tervaert JW, Deloukas P, Feighery C, Gross WL, Guillevin L,Gunnarsson I, Harper L, Hrušková Z, Little MA, Martorana D, Neumann T, Ohlsson S, Padmanabhan S, Pusey CD, Salama AD, Sanders J-S F, Savage CO, Segelmark M, Stegeman CA, Tesař V, Vaglio A, Wieczorek S, Wilde B, Zwerina J, Rees AJ, Clayton DG and Smith KGC. “Genetically Distinct Subsets within ANCA-Associated Vasculitis.” New England Journal of Medicine, 2012; 367:214-223.
Lee JC, Espéli M, Anderson CA, Linterman MA, Pocock JM, Williams NJ, Roberts R, Viatte S, Fu B, Peshu N, Hien TT, Phu NH, Wesley E, Edwards C, Ahmad T, Mansfield JC, Gearry R, Dunstan S, Williams TN, Barton A, Vinuesa CG; UK IBD Genetics Consortium, Parkes M, Lyons PA, Smith KGC. “Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway.” Cell. 2013; 155:57-69.
Gale DP, de Jorge EG, Cook HT, Martinez-Barricarte R, Hadjisavvas A, McLean AG, Pusey CD, Pierides A, Kyriacou K, Athanasiou Y, Voskarides K, Deltas C, Palmer A, Fremeaux-Bacchi V, de Cordoba SR, Maxwell PH*, Pickering MC. Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet. :376:794-801. 2010. [*corresponding author + joint senior author].
Takeda Y, Costa S, Delamarre E, Roncal C, De Oliveira RL, Squadrito ML, Finisguerra V, Bruyère F, Deschoemaeker S, Wenes M, Hamm A, Serneels J, Magat J, Bhattacharrya T, Anisimov A, BJordan BF, Alitalo K, Maxwell P, Gallez B, Zhuang ZW, Saito Y, Simons M, De Palma M, and Mazzone M. Macrophage skewing by PHD2 haplodeficiency prevents ischemia by inducing arteriogenesis. Nature 479:122-6. 2011.
Yang, J., Staples, O., Thomas, L.W., Briston, T., Robson, M., Poon, E., Simões, M.L., El-Emir, E., Buffa FM., Ahmed, A., Annear, N., Shukla, D., Pedley, B., Maxwell, P. H., Harris, A. L., Ashcroft, M. (2012). Human CHCHD4/MIA40 mitochondrial proteins regulate cellular oxygen consumption rate and metabolism, and provide a critical role in hypoxia signalling and tumour progression. J Clin Invest 122(2):600-11. doi: 10.1172/JCI58780. Feature article and front cover.
Al-Lamki RS, Sadler TJ, Wang J, Reid MJ, Warren AY, Movassagh M, Lu W, Mills IG, Neal DE, Burge J, Vandenebeele P, Pober JS, Bradley JR. Tumor necrosis factor receptor expression and signaling in renal cell carcinoma. Am J Pathol 2010; 177:943-54.
Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010; 363:211-20.
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. A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. Nature Med 2010; 16:586-591.
Willcocks LC, Carr EJ, Niederer HA, Rayner TF, Williams TN, Yang W, Scott JA, Urban BC, Peshu N, Vyse TJ, Lau YL, Lyons PA, Smith KG. A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus. Proc Natl Acad Sci USA 2010; 107:7881-5.
Clatworthy MR, Watson CJ, Plotnek G, Bardsley V, Chaudhry AN, Bradley JA, Smith KG. B-cell-depleting induction therapy and acute cellular rejection. N Engl J Med 2009; 360:2683-5.