The overall objective of this project is to develop a deep learning based imaging analysis and informatics tool for better understanding of pathogenic mechanisms in T1D, using existing data which has been collected for 14 years by Network for Pancreatic Organ Donors with Diabetes (nPOD) study. The central hypothesis of this proposal is that modifications […]
Category: Current nPOD Projects
Role of myosin-I in insulin secretion
In pancreatic beta cells, insulin is produced as proinsulin and packaged into secretory granules at a region of the cell called the trans-Golgi network (TGN). After maturation which includes the conversion of proinsulin to insulin, insulin granules are trafficked to the cell membrane where their contents are released through a process known as exocytosis. Actin […]
Evaluating senescence induction in human beta cells upon transplantation
We are interested in cell replacement therapy as a potential practical cure for patients suffering from diabetes. Using stem cell derived beta cell clusters and cadaveric human islets transplantation in preclinical animal models we find distinct changes to the beta cell phenotype. This project will test if our observations hold true in islet recipients. We […]
To identify T1D epitope using highly specific autoantibodies
DQ8/InsB:R3 was identified as an antigen by functional analysis of reactive T cells from peripheral blood, but direct evidence of antigenicity in islets is missing. The hypothesis is that the endogenous DQ8/InsB:R3 appear at the core organs of T1D in a disease stage-related timing. CODEX is a highly multiplexed tissue imaging platform enabling >50 markers […]
Identification and characterization of Coxsackievirus-reactive CD8+ T cells in pancreatic lymph nodes
Despite accumulating epidemiological and histopathological evidence for an association between Coxsackievirus B (CVB) and type 1 diabetes (T1D), a causal link is missing. Very little is known about the T-cell response mounted against CVB infection and the epitopes targeted. Moreover, the ongoing CVB vaccination trials require: 1) the development of T-cell biomarkers to follow vaccination […]
Therapeutic targeting of senescent β cells in Type 1 Diabetes
A growing body of evidence has implicated various forms of beta cell dysfunction in the pathogenesis of Type 1 Diabetes (T1D). Recently we discovered that during the natural history of T1D, a subpopulation of β cells become senescent. Senescence is a cell type-specific form of permanent growth arrest, which occurs during aging, tissue damage or […]
Changes in pericyte phenotype and function during type 1 diabetes
Endocrine cells in pancreatic islets are embedded in a network of blood vessels that support adequate nutrient sensing, efficient release of hormones, and timely responses to changes in glycemia. This network of islet blood vessels consists of capillary tubes made of endothelial cells that are covered by pericytes. Compelling evidence indicates that significant structural alterations […]
VDAC1 a Common Denominator of Pancreatic β-cell and Vascular Endothelial Cell Apoptosis in T1D and its Organ Complications
Impaired insulin secretion from the β-cells characterizes both type 2 and the initial phase of type 1 diabetes (T1D). Although the two sub-forms have different causes, we postulate that the rapidly developing β-cell defect and death in T1D as well as the slowly progressing β-cell dysfunction associated with T2D share a common cellular mechanism. Long-term […]