Improving adipose tissue (AT) insulin resistance and induce adipocyte browning are key therapeutic aims in the management of obesity associated insulin resistance (IR) and in type 2 diabetes (T2DM). Our laboratory has recently identified neuropeptide FF (NPFF) as a pancreatic hormone, which selectively improves IR in the AT and controls AT browning, especially in infancy […]
Category: Current nPOD Projects
Role of Monogenic Diabetes, Integrated Stress Response, mTOR and NR4A genes in Type 1 Diabetes
To date, over 60 loci have been identified, including the HLA and insulin regions and various single nucleotide polymorphisms (SNPs), conferring genetic susceptibility for type 1 diabetes (T1D); however, a number of these loci do not correspond to specific genes and as such, do not infer disease mechanisms or etiology. We have taken an innovative […]
Persistence of Pancreatic Insulin mRNA Expression and Proinsulin Protein and the Autoantigens GAD, IA-2 and ZnT8 in Type 1 Diabetes Pancreata
The canonical notion that type 1 diabetes (T1D) results following a complete destruction of β cells has recently been questioned as small amounts of C-peptide are detectable in patients with long-standing disease. Previously, we analyzed protein and gene expression levels for proinsulin, insulin, C-peptide, and islet amyloid polypeptide within pancreatic tissues from T1D, autoantibody positive […]
Role of bacterial biofilms in the onset of pancreas inflammation in T1D
Even though the immunopathogenic triggering event(s) in type 1 diabetes (T1D) remain enigmatic, there is accumulating evidence, mainly in rodent models of the disorder, suggesting that pancreas-resident antigen-presenting cells (APC) are activated very early post-natally. This results in the recruitment of innate immune cells like neutrophils into the pancreas even before adaptive immune cells that […]
Using Emerging Techniques to Identify Novel Islet Signatures in Type 1 and Type 2 Diabetes
Though the pancreatic islets are known to play critical roles in both Type 1 diabetes (T1D) and Type 2 diabetes (T2D), the distinct mechanisms are poorly understood. Recent findings demonstrate that chemical heterogeneity exists within the classic islet endocrine cell types, even in the normal/healthy pancreas setting. For example, there are subtypes of beta cells […]
Human T cell repertoire profiling in Type 1 Diabetes
Current strategies of studying islet autoantigen-specific T cells rely heavily on fluorescence labeled tetramers and are limited in the throughput of antigens that can be analyzed simultaneously. The profile of islet autoantigen-specific T cells that can be obtained is limited. We recently developed a new technology, Tetramer associated TCR sequencing (TetTCR-Seq), that is capable of […]
Highly Multiplexed Imaging Mass Cytometry of the Human Pancreas Affected by Type 1 Diabetes
Despite extensive efforts, understanding of the mechanisms of type 1 diabetes (T1D) development in human patients is collectively lacking, particularly with regard to contributions of islet endocrine cells, the immune system, and their interplay in the disorder’s development. Until recently, these questions have been particularly challenging to address due to technical limitations in the number […]
Analysis of cellular proteins in β cells from patients with type 1 diabetes and healthy
Our objective is to identify characteristics of β cells that survive immune attack. Our hypothesis is that these residual cells express immune inhibitory molecules and/or decrease expression of diabetes associated antigens. In addition, these cells may show changes consistent with dedifferentiated β cells. Our studies of protein modifications have also shown that there are post-translational […]
The role of protein kinase C delta in beta-cell death and dysfunction in type 1 diabetes
The goal of this study is identify novel mechanisms of immune-mediated β-cell death and dysfunction such that these mechanisms can be exploited to protect against the onset and progression of T1D. To achieve this goal, we propose the following aims: 1) Determine if reduced electrical coupling, altered calcium signaling, and activation of protein kinase C […]