Quality control–the removal of immune cells that have the ability to attack our own tissues–is a central tenet of the immune system. In type 1 diabetes (T1D), impaired quality control in the thymus, leads to release of beta cell–reactive immune cells (called T cells) into the blood; such cells facilitate destruction of insulin–producing beta cells […]
Year: 2024
Determination of RFX3 and RFX6 expression in human fetal, neonatal, childhood and young adult pancreas
The human pancreas is a vital organ responsible for both endocrine and exocrine functions, playing a crucial role in glucose metabolism and digestion. It originates from the foregut endoderm, with the dorsal and ventral buds forming and eventually fusing to develop into a mature pancreas. Key stages of pancreas development include specification, branching morphogenesis, and […]
Stromal sentinel cells are activated in T1D and organize tertiary lymphoid structures
Preliminary data indicates that stromal cells within the vicinity of islets acquire properties that can organize ectopic lymph node like structures (known as tertiary lymphoid structures or TLS) in NOD mice. These properties include differentiating of stromal cells into specific cell types that can secrete chemokines to organize infiltration of T and B cells and […]
Investigating the role of Hippo pathway in Type 1 Diabetes
The prevalence of type 1 diabetes (T1D) is on the rise, posing a significant burden on healthcare systems. T1D results from the immune system mistakenly attacking insulin–producing pancreatic β–cells, necessitating lifelong insulin treatment and continuous monitoring of blood sugar levels. The complex inflammatory nature of T1D, coupled with substantial gaps in our understanding of the […]
nPOD Data Portal
DATE: Friday, September 6th, 2024 TIME: 11:00AM EST Meeting Recording: Dropbox link to view recording Discussion led by: Helmut Hiller, MS & Maria Beery, MS In this webinar, we guided you through the nPOD Data Portal website, and showed you how to navigate, access, and download our new genetic data, including SNPs-genes and immunophenotyping data. […]
Defining the link between Islet prohormone accumulation and secretion in type 1 diabetes
An improved understanding of the pathophysiologic mechanisms contributing to insulin deficiency in type 1 diabetes (T1D) is crucial to optimize approaches to disease prevention and treatment. Multiple groups have described increases in beta cell prohormones in individuals at different stages of T1D development, both at the level of the islet and in circulation. These findings […]
Investigating the role of iron metabolism in beta cell function and the immunopathology of type 1 diabetes
Insulin release from beta cells depends on ATP energy generated by mitochondrial. The electron transport chain is the primary group of proteins that make ATP energy and they require iron to do so. Consequently, iron is essential for insulin release, and iron deficiency inhibits beta cell function. Conversely, excess cellular iron leads to an increase […]
Do enteroviruses trigger diabetes progression?
Identification of the driver of autoimmunity and early intervention before established disease is urgently needed. As in many autoimmune diseases, viral infections have been associated with T1D, recently confirmed by large and highly sensitive screenings using well–characterized material from autopsy and biopsy. We looked closer into the pancreases from organ donors with early T1D–associated autoimmunity […]
The Heterogeneity of Type 1 Diabetes: An Islets Story
When a person is diagnosed with Type 1 diabetes (T1D), the amount of beta–cell mass each individual loses is highly variable despite their clinical need for insulin therapy. Attempts to detect robust markers in the blood that precisely describe disease activity in the islets are ongoing, but without a full understanding of the disease course […]
The role of human ductal cells in propagating pathogenesis of type 1 diabetes
Type 1 diabetes (T1D) is a pancreatic disease marked by the autoimmune destruction of insulin–secreting beta cells within the endocrine compartment, leading to chronic hyperglycemia and long–term complications. Despite extensive studies into the autoimmunity that targets beta cells, a complete understanding of the pathogenesis of T1D remains unclear. A recent study by Fasolino et al. […]
T cell autoreactivity in pancreatic draining lymph nodes (pLN) of donors with cystic fibrosis-related diabetes (CFRD) and type 1 diabetes (T1D)
Many individuals with cystic fibrosis (CF) develop diabetes or CF–related diabetes (CFRD).Some published data indicates that CFRD shares autoimmune phenotypes in common with type 1 diabetes (T1D). These include a higher prevalence of islet autoantibodies for CFRD patients than the general population and signs of broad immune dysregulation (including a Th17 signature). Notably, in autoantibody–positive […]
Uridine in the pathogenesis of T1D
Blood uridine levels are elevated in T1D. However, its significance to the disease pathogenesis remains largely unexplored. Our pilot studies indicate uridine regulates glucose–stimulated insulin secretion (GSIS) in mouse and human islets. We will use human pancreas tissue sections and live pancreas slices to study how chronic elevation in blood uridine might affect beta cell […]
Leveraging heterogeneity to identify markers of resilient β-cells in T1D
We aim to identify factors contributing to the destruction ofβ–cells in diabetes. In this project, we took advantage of publicly available bulk and single cell gene expression datasets from human islets of healthy and diabetic donors(T1D and T2D). We used deep transfer learning platform DEGAS1 combinedwith this data to identify subsets of β–cells within human […]
Role of p21-activated secretory phenotype (PASP) in initiating type 1 diabetes pathogenesis
Type 1 diabetes (T1D) results from autoimmune insulitis destruction of insulin-secreting β cells. β cell senescence with upregulated expression of P21 has been observed in the adult NOD mice and new-onset patients. However, it remains unclear whether the beta cell senescence is an outcome of persistent insulitis, and the factors trigger insulitis remains unclear. The […]
De-differentiation of cryopreserved splenocytes to iPSC as an isogenic resource for differentiation to sc-islets. Addendum: De-differentiation of cryopreserved islet-derived T cell lines to iPSC as a resource for differentiation to sc-islets
In collaboration with the New York Stem Cell Foundation (NYSCF, see letter of collaboration), we will attempt de-differentiation of cryopreserved splenocytes to iPSC: this has not been attempted before to our knowledge. If successful, these iPSC may be differentiated into sc-islets and serve as an isogenic sources of sc-islets for interactions with the islet-derived T […]
Immediate-early gene transcription factor (IEG-TF) expression within human pancreatic islets during pregnancy and gestational diabetes
Pregnancy is a unique physiologic state in adult females that occurs and resolves over a defined time period. The acute metabolic stress it causes on the mother triggers adaptations with maternal pancreatic islets. Failure of normal islet adaptation is a major contributor to gestational diabetes (GDM).In rodents, insulin-producing beta-cells proliferate causing expansion of beta-cell mass. […]
The insulin secretory granule components and its immune recognition in type 1 diabetes
Our parent project studies the intracellular accumulation and molecular interaction of proinsulin, insulin and the proinsulin processing enzymes PC1/3, PC2 and CPE, which may be dysregulated during the development of the disease and lead to processing errors. Our interest was focused on proinsulin and insulin, as these are the most abundant molecules of the insulin […]
Spatio-temporal visualization of immune and non-immune islet injury in Type 1 Diabetes
Type 1 Diabetes (T1D) generally results from a poorly understood autoimmune process that leads to selective destruction of pancreatic beta cells. Interestingly, beta cell function is often not correlated with mass and declines very early in the disease before symptom onset, but the mechanisms driving this are not known. Islet beta cells existing in a […]