Research Projects

Type I Diabetes (T1D) is a complex autoimmune disease characterized by high blood glucose level due to destruction of insulin-secreting pancreatic beta-cells, mediated primarily by T cells. It mainly affects children, adolescents and young adults, and is an incurable lifelong disease. Despite several advances in insulin therapy, T1D management has not improved, patients still suffer from fluctuating glucose levels and its consequences including hypoglycemia, ketoacidosis, retinopathy, nephropathy, other microvascular complications, depression and reduced life-years. The disease etiology is not fully understood, it is thought to be triggered by environmental factors on a predisposed genetic background. India has the highest prevalence of T1D in children among South-East Asian countries, with about 10.5 cases/100,000 children annually. Genetic studies on T1D show conflicting reports between Caucasian and Asian populations, and due to limited studies among North and South Indian cohorts, further region-specific genetic research is needed in Indian context. Despite distinct environmental conditions, dietary habits, and infectious disease prevalence in the Indian subcontinent, epigenetic factors like DNA methylation and chromatin accessibility remain unstudied in Indian T1D patients. In the present study, we aim to study genetic association of immune-related genes with T1D in an Eastern Indian cohort. The recent increase in global incidence of T1D3 and the fact that ~85% cases arise without family history, motivated us to study epigenetic modifications associated with the disease. We plan to profile genome-wide chromatin accessibility patterns and DNA methylation, along with their transcriptome, in T cells from T1D compared to healthy individuals. Recent-onset cases will be evaluated for possible triggering epigenetic events. Long-standing cases will be assessed for epigenetic changes associated with T1D-related microvascular complications. Finally, genetic, epigenetic and transcriptome data from T cells of T1D and healthy control individuals will be integrated to improve understanding of T1D pathogenesis. T1D cases and matched healthy individuals will be recruited by our clinician collaborator, 5ml of blood sample will be collected. DNA extracted will be used in genetic association study. T cells isolated will be used for DNA methylation and chromatin accessibility studies, while RNA will be used for transcriptome analysis. Since T1D is clinically diagnosed after substantial beta-cell loss, identifying risk factors may enable early diagnosis and intervention. As genetic and DNA methylation changes linked to T1D can be detected before autoantibodies arise, they can serve to identify predisposed individuals among Indian context, and can also be related to complications in long-term cases. Combined genetic, epigenetic and transcriptome study will thus enhance understanding of T1D, and can benefit disease management.