Our research aims to investigate how a group of adult stem cells, known as mesenchymal stem /stromal cells(MSCs), located in the pancreas may be involved in helping to protect people from developing type 1 diabetes(T1D). MSCs are found in most parts (tissues) of the body, including the pancreas, bone marrow, fat and kidney. When samples […]
Category: Current nPOD Projects
Quantitative proteomic profiling of human islets in healthy and diabetes associated pregnancy
Normal pregnancy is associated with a rise in insulin secretion, which begins at placental implantation and increases progressively in parallel with placental growth. Following placenta delivery there is a sharp postpartum decline in insulin secretion. Gestational diabetes (GDM),the development of diabetes for the first time during pregnancy, is associated with pancreatic beta-cell dysfunction. Rodent models […]
Identification of protective niches in T1D pancreata
Type 1 diabetes (T1D) is caused by an autoimmune attack mediated by cytotoxic T cells. However as the attack unfolds, many other cell types participate–and some play an anti-inflammatory, regulatory, role. Interestingly, in the early stages of the disease, attacked islets often reside next to non-attacked islets. We hypothesized that the “tranquil” islets harbor elements […]
Changes in human islet microvasculature during the progression of type 1 diabetes
The pancreatic islet is surrounded by an extracellular matrix (ECM) composed of laminin, collagen IV, and proteoglycans, that support islet function and viability. Type 1 diabetes (T1D) is characterized by the immunemediated loss of insulin-producing β-cells in the islet. Islet infiltration by activated immune cells results in the degradation of the peri-islet ECM eliminating critical […]
Age-related heterogeneity of type 1 diabetes: a multi-omics, spatially resolved, exploration of the human pancreas at disease onset
Type 1 diabetes (T1D) is a chronic autoimmune disease long thought to primarily affect children and adolescents. However, recent data suggest that nearly 70 percent of new T1D cases occur in adults. Striking differences in genetic, metabolic, and immune features as well as in diabetes management have been described between childhood- and adult-onset T1D, but […]
Pathogenic Action of Autoantibodies on Islet Function and Viability in Type 1 Diabetes
Type 1 Diabetes (T1D) is known to develop over time when autoimmune processes attack and destroy beta cells thereby reducing the capacity to secrete adequate amounts of insulin. The relatively gradual progression of the disease offers an opportunity for therapeutic intervention to slow or prevent destruction of beta cells before the disease has reached symptomatic […]
Mapping islet B cells in the pancreas on a single-cell level
Recent evidence suggests a role for B cells in the pathogenesis of type 1 diabetes (T1D), particularly in individuals who develop T1D at a younger age and demonstrate rapid progression. However, little is known regarding the specificity, phenotype, and function of B cells in young-onset T1D. Recently we performed a cross-sectional analysis comparing insulin-reactive to […]
Unraveling the Role of CD45RA+CCR7+CD4 T Cells in the Pathogenesis of Type 1 Diabetes
This study aims to investigate the role of CD45RA+CCR7+CD4 T cells in the pathogenesis of type 1 diabetes (T1D). Historically, naïve T cells were deemed irrelevant in T1D development due to their presumed lack of antigen experience. However, distinct subsets of naïve T cells with varying phenotypes and functions have been identified, with recent literature […]
Unbiased single cell resolution spatial proteomics: defining the antigenic landscape in the context of HLA-I expression during type 1 diabetes progression
Diabetes is a complex metabolic disease in which patients experience high blood glucose levels leading to a plethora of symptoms and long-term complications. In type 1 diabetes (T1D), this happens likely due to an autoimmune reaction targeting the insulin producing cell population, so-called beta cells, within the pancreatic islets. CD8+ T-cells are considered the main […]
CD6 and its ligands in Type 1 Diabetes
Type 1 diabetes mellitus (T1D) results from the autoimmune attack of pancreatic β-cells, resulting in a loss of functional β-cell mass. The CD6 molecule is a membrane glycoprotein predominantly expressed on T cells and is implicated in lymphocyte adhesion, activation, and proinflammatory commitment. The CD6 ligand CD166/ALCAM is upregulated in mature dendritic cells and the […]
Targeting the innate immune system to discover new therapeutic pathways for the prevention of type 1 diabetes
Type 1 diabetes (T1D) is an autoimmune disease, where immune cells (T cells) of the body attack and destroy the insulin-producing beta cells. T1D is, if left untreated, a devastating and life-threatening disease and despite intensive research in the field, there are still missing pieces in the pathogenetic puzzle of the disease. With this project, […]
IAPP and innate immunity in T1D
Islet amyloid polypeptide (IAPP) is a beta-cell peptide hormone that forms toxic and pro-inflammatory aggregates in pathological states, including T2D and islet transplants. Recent evidence suggests the presence of fibrillar aggregates of IAPP (islet amyloid) in some T1D pancreatic islets. In T2D and mouse models of islet amyloid formation, aggregates of human IAPP recruit and […]
Analysis of innate immune response of myeloid cells in human Type 1 diabetes
Type 1 diabetes (T1D) is a multifactorial autoimmune disease that requires genetic susceptibility as well as environmental triggers to induce disease onset. Genetic association studies have implicated the IFIH1 gene, encoding for melanoma differentiation-associated protein 5 (MDA5), a cytosolic sensor of dsRNA, to be involved in T1D susceptibility and resistance. Stimulation of the MDA5 signaling […]
Role of Alpha Cells in Pathogenesis of Type 1 Diabetes
Multiple islet autoantibodies (AAb+) predict type 1 diabetes (T1D) and hyperglycemia within 10 years. By contrast, T1D develops in just ~15% of single AAb+ (generally against glutamic acid decarboxylase, GADA+) individuals; hence the single AAb+ state may represent an early stage of T1D. We previously discovered the functional defects in suppression of glucagon secretion in […]
Congruence of lab versus histopathologic findings of acute pancreatitis in the nPOD consortium
Acute pancreatitis is the cause of more than 200,000 hospital admissions in the United States each year (1). Acute pancreatitis presents very broadly, hence diagnosis can be difficult and requires confirmatory tests. Serum amylase and lipase levels have been established as markers for disease. However, they lack adequate specificity and sensitivity which might make their […]
Stellate cells in type 1 diabetes research (STELLAR)
The loss of insulin-producing β-cells is central to the pathogenesis of type 1 diabetes (T1D). More recently, the contribution of the exocrine pancreatic cellular components is becoming evident in determining the β-cells well-being. Other pancreatic cell types could be acting by reducing β-cell resistance to the autoimmune attack or inducing a stressful condition that will […]
Redoxins in the pathogenesis of type 1 diabetes
We plan to quantify redoxin expression levels and the frequency and type of redoxin expressing pancreatic cells by imaging procedures established in our group. For this purpose we propose a pilot study with samples from #3 cases ideally with rapid (pre-type 1 or type 1 diabetes) or more chronic (type 2 diabetes) ongoing beta cell […]