Circulating Extracellular Vesicles in the Pathogenesis of Type 1 Diabetes

  • Vasavada, Rupangi R.C (PI)
  • Sahoo, Susmita (CoPI)
  • Sahoo, Susmita S (CoPI)
  • Vasavada, Rupangi (CoPI)

Project Details

Description

SUMMARY: Circulating Extracellular Vesicles in the Pathogenesis of Type 1 Diabetes Type 1 diabetes (T1D) is an autoimmune disease, characterized by death, dedifferentiation or dysfunction of functional beta cells. However, precise molecular events that initiate beta cell loss and dysfunction or mediate autoimmunity is a major gap in knowledge that remains unaddressed. Emerging evidence suggests that circulating extracellular vesicles (EVs), known mediators of intercellular microcommunication, may play important roles in the pathogenesis of T1D. However, their precise function and molecular contents, especially in the initiation of beta cell loss and dysfunction in humans are largely undefined. Here, we hypothesize that circulating EVs in T1D, through their distinct molecular characteristics, are cytotoxic to beta cell health, thus contributing to the pathogenesis of T1D, with the potential to serve as biomarkers for early disease diagnosis. Our preliminary data suggests that EVs, but not EV-depleted fraction in the humoral factors in T1D are cytotoxic, particularly to human beta cells, but not to alpha cells. Specifically, EVs from T1D subjects, but not from control subjects, induce human beta cell death suggesting that circulating T1D-EVs are key components contributing to humoral cytotoxicity. Therefore, characterizing T1D EVs at various stages of the disease and control could identify important biomarkers for early detection of the disease that correlate with beta cell loss and dysfunction. Our research plan has the following Specific Aims: AIM 1: To determine the functional effects of circulating EVs from pre-disease to late stage T1D subjects on human beta and alpha cell health. We will characterize circulating EVs from the plasma of T1D subjects at i) early (1-5 years), ii) late (>10 year) and iii) pediatric (
StatusActive
Effective start/end date24/08/2131/05/23

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases: $480,618.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $461,618.00

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