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John Todd

John Todd

Research groups

Collaborations

John Todd

FRS, FMedSci, FRCP (Hon), PhD


Professor of Precision Medicine

JDRF/Wellcome Diabetes and Inflammation Laboratory (DIL)

John Todd is Professor of Precision Medicine at the University of Oxford and Director of the Wellcome Centre for Human Genetics and of the JDRF/Wellcome Diabetes and Inflammation Laboratory (DIL). He is also an Emeritus Senior Investigator of the National Institute for Health Research. Until 2016 he was Professor of Medical Genetics at the University of Cambridge and prior to this, Professor of Human Genetics and a Wellcome Trust Principal Research Fellow at the University of Oxford. His PhD was in Biochemistry at the University of Cambridge, followed by a postdoctoral fellowship at Stanford University. Todd helped pioneer genome-wide genetic studies in common diseases and then went on to study the associations between disease-associated genetic variants and phenotypes in T1D by founding and deploying the Cambridge BioResource. He researches type 1 diabetes (T1D) genetics and disease mechanisms with the goal of delivering clinical interventions.

In the latest phase of his research, to translate basic genetic and immunological knowledge to treatment and prevention, the DIL is testing the efficacy of ultra-low doses of interleukin-2 in newly-diagnosed children with T1D to preserve the remaining pancreatic islet beta-cell insulin production and investigating the role of the microbiome in T1D. Todd is also part of the international consortium, Global Platform for the Prevention of Autoimmune Diabetes (GPPAD), aiming to establish primary preventions of T1D in randomised placebo-controlled trials, initially by testing the possibility that daily oral insulin given to children at high genetic risk of T1D can inhibit the autoimmunity that causes T1D. His research in genetics and diabetes has received several awards and prizes, including the 1995 Minkowski Prize of the European Association for the Study of Diabetes (EASD) and the 2021 EASD/Novo Nordisk Foundation Diabetes Prize for Excellence. Todd has supervised 40 PhD and MSc students with three in progress and has an h-index of 131 and over 80,000 citations.

Further details about the DIL: The DIL is led by John Todd (Director) and Linda Wicker (Co-Director). We are researching the causes of the autoimmune disease type 1 diabetes (T1D) in order to treat and prevent the disease by modulating the causative pathways.  We achieve this by linking genetic determinants of disease with phenotypes and pathways in cells and in patients, using a wide range of molecular, metabolic, immunological, computational and statistical approaches.

Genetics: identification of T1D genes and their pathways is essential for understanding the biology underpinning disease susceptibility. We are integrating the latest and emerging genomics data - genetic variation, RNA and protein gene expression, methylation, transcription factor binding sites and chromatin phenotypes – to better define the T1D causal genes. 

Phenotypes and mechanisms: identify aberrant cellular interactions and pathways caused by susceptibility genes that mediate a loss of immune tolerance to insulin-producing beta cells culminating in their destruction.  These will provide potential targets for therapeutic intervention, as demonstrated by our work in the IL-2 pathway. This knowledge will contribute to understanding cell interactions altered by disease genes, an essential step for prioritizing potential immune-modulating agents to be investigated in experimental studies in T1D patients. 

Experimental medicine: our hypothesis is that determination of the optimal dosing regimen of a potential therapeutic in terms of its molecular and cellular responses in vivo will greatly improve the likelihood of a beneficial outcome in future clinical trials. We are testing the utility of this approach in the ongoing investigation of the effects of ultra-low doses of IL-2 in patients with T1D, and will consider and evaluate other potential therapeutics.  Secondly, we are part of an randomised control trial for primary prevention T1D in children in the population by feeding newborn children oral insulin every day for three years to promote immune tolerance to insulin, the primary autoantigen in T1D.  Thirdly, we are planning investigation of the enhancing the healthy state, including improving tolerance to insulin through cross reactivity with a commensal antigen that we have discovered, of the intestinal microbiome using combinations of bacterial probiotics and prebiotics, in the context of deep microbiome genome sequencing and interactions with the HLA class II genotypes that increase and decrease risk of autoimmune responses to insulin and to T1D.

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