Diabetes and Inflammation Laboratory
The JDRF/Wellcome Trust Diabetes and Inflammation Laboratory (DIL) is led by John Todd (Director) and Linda Wicker (Co-Director). The lab is researching the causes of the autoimmune disease type 1 diabetes (T1D) with the aim of modulating the causative pathways to treat and prevent the disease. Our strategy is to link genetic determinants of disease with phenotypes and pathways in cells and in patients, extending this to experimental medicine/translational studies that evaluate potential therapeutics. Many of our approaches, methods and results provide paradigms for more precise interventions in other common diseases.
Genetic 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 to better define the T1D causal genes. From the susceptibility genes, we can identify aberrant cellular interactions and pathways that lead to a loss of immune tolerance to beta cells culminating in their destruction, thereby providing potential targets for therapeutic intervention, as demonstrated by our work in the IL-2 pathway. In addition, we are developing and using single-cell platforms to phenotype immune cells and investigate immune cell populations in tissues. Our interest in other possible mechanistic pathways extends to those that involve the gut microbiome as well as the potential mechanistic similarities between neuronal loss in neurodegenerative diseases and beta-cell dysfunction in T1D.
We actively participate in clinical studies. Our first two trials established the dose and frequency for the drug for human IL-2, aldesleukin, and have informed the current IL-2 Therapy in Autoimmune Diabetes (ITAD) trial to test whether the aldesleukin dosing regimen can slow the decline of insulin secretion in newly-diagnosed children. We are part of an international consortium, GPPAD, which provides the infrastructure to conduct trials to prevent T1D. Its first trial, ‘POInT’, is based on the daily administration of oral insulin in children at high genetic risk of T1D to determine if this can inhibit the autoimmunity that causes T1D. We are also part of the pan-European Consortia Innodia and Innodia Harvest. We collaborate with companies Bristol Myers Squibb and UCB.
The DIL is organised around teams carrying out specific tasks related to the above activities as well as project-focused groups of researchers. We work collaboratively within DIL and with Oxford-based and international researchers.
Core support of the DIL is provided by a Strategic Award jointly funded by Wellcome and the JDRF. We are grateful for recent additional support provided by the 2021 EASD/Novo Nordisk Foundation Diabetes Prize for Excellence which was awarded to Professor John Todd. The DIL relocated to Oxford from Cambridge in March 2016.
Potential project areas: Diabetes, autoimmunity, genomics, single cell omics, genetics, statistics, bioinformatics, immunology, experimental medicine, clinical trials.
Trzupek D. et al, (2021), Wellcome Open Research, 6, 149 - 149
Robertson CC. et al, (2021), Nature genetics
Ahern DJ. et al, (2021)
Collier DA. et al, (2021), Nature, 593, 136 - 141