Professor of Clinical Immunology Honorary Consultant Immunologist at King’s College Hospital NHS Foundation Trust
Lead for Cluster 1 (Experimental Medicine and Therapeutics) in the NIHR Biomedical Research Centre
Our work focuses on type 1 diabetes, a disease that is widely considered to be the result of a chronic autoimmune process that leads to the death of insulin-producing β-cells in the islets of Langerhans. Type 1 diabetes is an important clinical burden worldwide, exemplified by its cost to the UK economy of £1.9 billion/year. The UK has ~400,000 patients (>50% diagnosed as children) and the world’s 5th highest incidence, still predicted to rise annually by 2-3%. Beyond being a life-changing diagnosis, the disease carries a burden of chronic complications (renal failure, loss of sight, cardiovascular disease) and early mortality (average 11-year reduction in life-expectancy). Understanding immune pathways that lead to disease and its progression could foster new therapeutic approaches, leading to early prevention or intervention strategies that maximize preservation of β-cells.
At its heart, type 1 diabetes is a result of a poorly-regulated immune system, in which autoreactive CD4 and CD8 effector T cells and B cells are able to combine to form an inflammatory focus in the islets (insulitis) that directly leads to β-cell death. The research in our group tries to understand what might precipitate this process; the role of genetic predisposition; the molecular and cellular requirements for β-cell killing (especially in terms of epitope recognition) and how healthy immune regulation to β-cells operates. At a more translational level we are aiming to develop new therapeutic strategies and better ways to monitor disease through immunological biomarkers and surrogates.
Arif, S., P. Leete, V. Nguyen, K. Marks, N. M. Nor, M. Estorninho, D. Kronenberg-Versteeg, P. J. Bingley, J. A. Todd, C. Guy, D. B. Dunger, J. Powrie, A. Willcox, A. K. Foulis, S. J. Richardson, E. de Rinaldis, N. G. Morgan, A. Lorenc and M. Peakman (2014). "Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes." Diabetes 63(11): 3835-3845. doi: 10.2337/db14-0365
Bulek, A. M., D. K. Cole, A. Skowera, G. Dolton, S. Gras, F. Madura, A. Fuller, J. J. Miles, E. Gostick, D. A. Price, J. W. Drijfhout, R. R. Knight, G. C. Huang, N. Lissin, P. E. Molloy, L. Wooldridge, B. K. Jakobsen, J. Rossjohn, M. Peakman, P. J. Rizkallah and A. K. Sewell (2012). "Structural basis for the killing of human beta cells by CD8(+) T cells in type 1 diabetes." Nat Immunol 13(3): 283-289. doi: 10.1038/ni.2206
Collison, J. L., L. M. Carlin, M. Eichmann, F. Geissmann and M. Peakman (2015). "Heterogeneity in the Locomotory Behavior of Human Monocyte Subsets over Human Vascular Endothelium In Vitro." J Immunol 195(3): 1162-1170. doi: 10.4049/jimmunol.1401806
Gibson, V. B., T. Nikolic, V. Q. Pearce, J. Demengeot, B. O. Roep and M. Peakman (2015). "Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized model." Clin Exp Immunol 182(3): 251-260. doi: 10.1111/cei.12687
Peakman, M. and A. K. Sewell (2015). "Reversed-polarity T(reg) cell TCRs provide a shock." Nat Immunol 16(11): 1105-1107. doi: 10.1038/ni.3289
Skowera, A., K. Ladell, J. E. McLaren, G. Dolton, K. K. Matthews, E. Gostick, D. Kronenberg-Versteeg, M. Eichmann, R. R. Knight, S. Heck, J. Powrie, P. J. Bingley, C. M. Dayan, J. J. Miles, A. K. Sewell, D. A. Price and M. Peakman (2015). "beta-cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure." Diabetes 64(3): 916-925. doi: 10.2337/db14-0332
Sobolev, O., E. Binda, S. O'Farrell, A. Lorenc, J. Pradines, Y. Huang, J. Duffner, R. Schulz, J. Cason, M. Zambon, M. H. Malim, M. Peakman, A. Cope, I. Capila, G. V. Kaundinya and A. C. Hayday (2016). "Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events." Nat Immunol 17(2): 204-213. doi: 10.1038/ni.3328