Cambridge Institute for Medical Research

Professor John Todd

Professor John Todd

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Identification of Molecular and Cellular Mechanisms in Autoimmune Disease

Our aim is to further characterise the molecular basis for the autoimmune inflammatory disease type 1 diabetes.  We use an integrated combination of genetics, in large collections of type 1 diabetic families and case/control, statistics, genome informatics and data mining, and gene expression and immunological studies.  Our major effort now is to correlate susceptibility genotypes with biomarkers and phenotypes e.g. we have associated flow cytometric phenotypes of T lymphocytes with disease-predisposing genotypes of the IL-2RA (CD25) gene (Dendrou, C. et al.  Nat. Genet. 41, 1011-1015, 2009).  This is a first step towards identifying disease precursors that could be used in future therapeutic studies to stratify patients.  To achieve this we have helped build a local biobank of volunteers and patients in whom we can study the effects of disease-associated genotypes and environmental factors (Cambridge BioResource: www.cambridgebioresource.org.uk/).  These immunology studies are underpinning the next major phase of our research: undertaking clinical studies and trials in patients with type 1 diabetes.  Our first clinical investigations will be to assess the effects and mechanisms of ultra-low dose IL-2 on the immune system, with a focus on T regulatory cell activities.  Our research efforts are part of the JDRF/Wellcome Trust Diabetes and Inflammation Laboratory (DIL), which has three other principal investigators, Linda Wicker (Co-director, DIL), Frank Waldron-Lynch (Clinical Research) and Chris Wallace (Head of Statistics group).

Funding

  • JDRF
  • National Institutes of Health (USA)
  • National Institute for Health Research Cambridge Biomedical Research Centre via University NHS Foundation Trust
  • Medical Research Council (MRC Next Generation Sequencing Hub Facility)
  • European Union (FP7 Framework Programme)
  • Wellcome Trust.

 

Group Members

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Charlie Bell
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Xaquin Castro Dopico
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Jason Cooper
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Nicholas Cooper
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Tony Cutler
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Marina Evangelou
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Ricardo Ferreira
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Saleha Hassan
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Marcin Pekalski
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Corina Shtir
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Austin Swafford
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Whitney Thompson

 

JDRF/Wellcome Trust Diabetes and Inflammation Laboratory

The JDRF/Wellcome Trust Diabetes and Inflammation Laboratory (DIL) has four Principal Investigators and is composed of four integrated research efforts: John Todd (human genetics and immunology), Linda Wicker (mouse modelling, human immunology), Chris Wallace (statistics) and Frank Waldron-Lynch (clinical studies and trials).  In the last five years we have been  correlating the presence of the identified susceptibility alleles with their functions to determine which molecules and pathways are underlying the pathogenesis of type 1 diabetes.  Our recent results have shown how important the interleukin-2 pathway is in autoimmunity and type 1 diabetes, and we are exploring further these mechanisms and their possible implications for new, mechanism-based therapeutic strategies.  Our clinical translational research is significantly enabled by the NIHR Biomedical Research Centre in the Clinical School (http://www.cambridge-brc.org.uk/), including key core facilities such as state-of-the-art flow cytometry, the Cambridge BioResource for recruitment of patients to our studies, Clinical Trials Unit and a Clinical Research Facility. Immunological and gene-phenotype studies have been strengthened by collaboration with a second JDRF Centre in the UK: Diabetes Genes, Autoimmunity and Prevention (D-GAP), which supports collaborations with Mark Peakman, Tim Tree, David Dunger and Polly Bingley. Investigations of therapeutic strategies in type 1 diabetes are also supported by a collaborative project funded by the European Union’s 7th Framework Programme (FP7), Natural immunomodulators as novel immunotherapies for type 1 diabetes (NAIMIT), and funding for a Phase II trial of ultra-low dose IL-2 in newly diagnosed type 1 diabetes in collaboration with Professor David Klatzmann (Paris).

Group Members

Administration and Research Management
Judy Brown (Head)
Louise Bell
Jenny Newton
Bart Philipczyk
Anna Simpson
Niall Taylor

Clinical Research
Frank Waldron-Lynch

Data Services
Neil Walker (Head)
Nigel Ovington
Helen Schuilenburg

Genome Informatics
Oliver Burren (Head)
Premanand Achuthan
Richard Coulson
Ellen Schofield

Research Group (Todd)
Charlie Bell
Xaquin Castro Dopico
Jason Cooper
Nicholas Cooper
Tony Cutler
Marina Evangelou
Ricardo Ferreira
Saleha Hassan
Marcin Pekalski
Corina Shtir
Austin Swafford
Whitney Thompson

Research Group (Wicker)
Jan Clark
Laura Esposito
Sarah Howlett
Dan Rainbow
Kara Rainbow

Research Group (Wallace)
Hui Guo
Nikolas Pontikos
Xin Yang

 

Sample Informatics
Matt Woodburn (Head)
Matthias Haimel
Carola Kanz
Krishna Mohan
Jakub Pawlinski

Sample Processing
Helen Stevens (Head)
Pamela Clarke
Gillian Coleman
Sarah Dawson
Jennifer Denesha
Simon Duley
Meeta Maisuria-Armer
Trupti Mistry

Statistics
Chris Wallace (Head)
Jason Cooper
Marina Evangelou
Hui Guo
Nikolas Pontikos
Corina Shtir
Xin Yang

Systems Management
Vin Everett (Head)
Wojciech Giel
Sundeep Singh Nanuwa

Genotyping and Sequencing
Debbie Smyth

Affiliates

Cambridge BioResource
Sarah Nutland (Head)
Kelly Beer
Chris Coner
Tracy Cook
Simon Hacking
Alison Hayday
Jamie Rice
Rachel Simpkins
Hannah Stark