The Centre of Diabetes is located in the Blizard Building. The Centre Lead is currently Prof. Malcolm Alison (rotating position).

The Centre has a major interest in genetic susceptibility to diabetes and related disorders and has developed excellent collaborations and unique clinical resources that allow it to continue to maintain a leading position. We are at the forefront of the international gene discovery programs in these disorders (including genome-wide association scans, candidate genes, functional genomics and applied physiology) and many seminal discoveries have been made. The establishment and activities of the Diabetes Local Research Network (LRN) will ensure the Centre is a major force in the delivery of a translational agenda of this discipline in East London.

A significant effort is focussed on immunomodulation studies that utilize an impressive clinical resource. We are focusing on genes important to inflammation and pancreatic beta cells from a number of major resources including British/Irish as part of the Diabetes UK/MRC Warren2 collections and from the South Asian subcontinent including younger adult patients from Bangladesh. We also study unique patient cohorts of British twins with diabetes and European adults with autoimmune diabetes. Focusing on genotype-epigenotype-phenotype relationships between and within these cohorts including studies of cellular and humoral immunity. We wish to understand how epigenetic mechanisms influence complex phenotypes and diseases and we are using functional genomics to explore the notion of the ‘epiallele' – loci at which the epigenetic state varies as a result of genetic and/or environmental influences.

Principal Investigators lead individual but overlapping key areas namely; genomic medicine (Prof. Graham Hitman), epigenetic medicine and biology (Dr. Vardhman Rakyan, Prof. David Leslie, Prof. Graham Hitman), trafficking in insulin secreting b-cells and protein sorting in the secretory phase (Dr. Mark Turner), immunogenetic, immunotherapy and autoimmune aspects of diabetes (Prof. David Leslie, Prof Paolo Pozzilli, Dr. Vardhman Rakyan, Dr. Mark Turner & Prof. Graham Hitman), insulin resistance and secretion (Prof. Mary Sugden & Dr. Mark Holness), obesity research and diabetes prevention strategies (Dr Simon Coppack & Prof. Graham Hitman), insulin signalling in muscles, b cells and pancreatic cancer (Prof. Marco Falasca & Dr. Tania Maffucci) and stem cells in pancreatic pathology (Prof. Malcolm Alison). We have new developments in PI3 kinase signalling pathways regulating intracellular processes including insulin production and secretion, insulin action in muscles and adipocytes, lipids and lipoprotein action on endothelial cells and growth factor-dependent effects on cell proliferation, survival and migration. Studies of insulin action and secretion in metabolic and cardiovascular disease focus on abnormalities of metabolic homeostasis introduced by lifestyle factors  (altered dietary composition, non-genetic obesity, pregnancy, exposure to cytokines) that increase the risk of developing T2D, gestational diabetes and cardiovascular disease. Research in stem cell biology exploits novel techniques based on mitochondrial mutations to identify stem cell-derived clonal populations of cells in the human tissues.

Major Achievements

• Discovery, as part of a consortium, of novel genes associated with type 2 diabetes using a genome wide association scan. (Nat Genet 2008; 40:638-45).

• Set up with NPRI and DOH support a diabetes prevention program involving the local Bangladeshi population.

• Identification of adult onset autoimmune diabetes as the most prevalent form of the disease.
(Centre Lead for Acton LADA EU project).

•  Development of vaccination strategies to limit islet cell damage in autoimmune diabetes.

• Identification of novel intracellular signalling pathways in b-cell function

• Identification of the role of a key enzyme (phospholipase Cg1) in pancreatic adenocarcinoma metastasis development.

•  The most downloaded dataset in the ENSEMBL genome browser. ‘An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Rakyan VK, et al. Genome Res 2008; 18:1518-1529’.

Future Objectives

We aim to expand our basic research in genomic and epigenetic medicine, cell biology and translational medicine into clinical research that will have direct benefit to patients, e.g. recently funded primary prevention programs in type 2 diabetes and autoimmune diabetes. Priorities for our basic research program are to develop an integrative approach to genomic medicine making use of our rich clinical resources and combined expertise in gene discovery, epigenetics and functional genomics (including cell signalling).

Enquiries in the first place should be addressed to Mrs Irene Smith, Administrator, Centre for Diabetes, Blizard Institute, 4 Newark Street, London E1 2AT. Email: i.m.smith@qmul.ac.uk; Tel: 020 7882 2369.

Forthcoming invited lectures:
Malcolm Alison is guest of the Taiwanese Gastroenterology Society in Taipei (March 4-7th), and invited lecturer at the 8th European Neuroendocrine Tumour Society in Lisbon (March 10-11th) and ‘Spotlight’ speaker at the 10th ESO Masterclass in Clinical Oncology in Ermatingen, Switzerland (2-7 April).

David Leslie is guest of Chinese Immunology of Diabetes Symposium in Changsha, China (April 28-30th); Immunology of Diabetes Society committee member on LADA; examiner MB final exams, Chinese University, Hong Kong (May 23-30th).