Decio L. Eizirik
Beta cell splicing signature in diabetes.
diabetes • endocrinology • alternative splicing
Decio L. Eizirik is professor at the ULB Center for Diabetes Research, Université libre de Bruxelles. His research aims to understand the pathogenesis of type-1 diabetes (T1D), more specifically the role of diabetes genes, endoplasmic reticulum stress and alternative splicing in pancreatic β cell deficiencies.
His project is focused on alternative splicing, a process that affects more than 90% of human genes. This provides cells with an extraordinary capacity to modify their transcriptome and proteome in response to intra- and extra-cellular signals. By producing new proteins, the cells can generate new epitopes, which may contribute to triggering an immune response. During his previous WELBIO project, Decio L. Eizirik has shown that the pro-inflammatory cytokines interleukin beta and interferon gamma, which are released by immune cells in pancreatic islets at the advanced stages of insulitis, change the expression of alternative splicing-regulating proteins. Consequently, a large amount of splicing variants are produced in β cells. This leads to the generation of neo-antigens, which are recognised by cytotoxic T lymphocytes invading the islets of patients with type-1 diabetes, thus amplifying the autoimmune assault.
This new project aims to characterise the alternative splicing regulatory networks and to identify the mRNA splice variants acting as neo-epitopes for T-cell activation. These variants will be validated as biomarkers for disease and as potential targets for new treatments based on splicing modulations.