Our mission is to improve understanding of pancreatic islet cell dysfunction in type 2 diabetes using human genetics as a tool to uncover causal disease mechanisms and shed light on potential targets for therapeutic development.
The group is based jointly at the Oxford Centre for Diabetes, Endocrinology & Metabolism and the Wellcome Trust Centre for Human Genetics. Working very closely with the team of Professor Mark McCarthy, we aim to understand the genetic basis of diabetes and related metabolic conditions and to use this to leverage a better understanding of what causes diabetes and how we can improve treatment options for patients. Our work is predominantly focused on understanding what causes pancreatic islets to release insufficient insulin to control blood glucose levels after a meal in patients with type 2 diabetes, but often extends to efforts to relate this to metabolic dysfunction in other relevant tissues such as fat and liver.
We are an inter-disciplinary team of basic and clinical scientists with shared interests in using molecular genetics as a tool to uncover novel biology. We use a variety of different approaches to address important challenges in the field, which range from studies that work genome wide to those which are focused on specific genes and even precise nucleotide changes to understand their impact on pancreatic islet biology.
We have developed a series of pipelines that use primary human islets and authentic beta-cell models which allow us to generate and then integrate complex genomic, transcriptomic and cellular datasets. We use state-of-the art genome engineering approaches combined with induced pluripotent stem-cells to study the impact of T2D-associated genetic variants on islet cell development and function. We are also funded to investigate the impact of T2D risk variants on pancreatic beta-cell function in vivo. We are able to recruit individuals with specific genotypes from the Oxford BioBank for detailed physiological investigations that we perform in the Oxford NIHR BRC funded Diabetes & Metabolism Clinical Research Unit in OCDEM. These studies allow us to study the impact of T2D-risk variants on beta-cell dysfunction in humans.
We are a highly collaborative team and work with multiple national and international consortia involved in efforts to understand the genetic basis of type 2 diabetes (eg DIAGRAM , NIDDK Funded Accelerated Medicines Partnership) and related glycaemic traits (MAGIC). We are also part of several Innovative Medicines Initiatives (IMIs) efforts including STEMBANCC and RHAPSODY and Horizon 2020 initiatives (eg T2DSYSTEMS), which are working to develop tools and frameworks to capitalise on genetic and genomic data.