A5004980895- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Genomics and Chromatin Dynamics
- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- Cannabis and Cannabinoid Research
- Hearing Loss and Rehabilitation
- Bioinformatics and Genomic Networks
- Genetics and Neurodevelopmental Disorders
- Ear Surgery and Otitis Media
- Schizophrenia research and treatment
- Immune Cell Function and Interaction
- Regulation of Appetite and Obesity
- Functional Brain Connectivity Studies
- Diet, Metabolism, and Disease
- Diabetes Treatment and Management
- Hearing, Cochlea, Tinnitus, Genetics
University of California, Davis
2016-2024
Indiana Biosciences Research Institute
2024
Indiana University – Purdue University Indianapolis
2024
Indiana University School of Medicine
2024
Center for Neurosciences
2016
Complex local crosstalk amongst endocrine cells within the islet ensures tight coordination of their output. This is illustrated by recent demonstration that negative feedback control delta pancreatic islets determines homeostatic set-point for plasma glucose during mouse postnatal development. However, close association facilitates paracrine also complicates distinction between effects mediated directly on beta from indirect via intermediates, such as somatostatin cells.To resolve this...
Islet gene expression has been widely studied to better understand the transcriptional features that define a healthy β-cell. Transcriptomes of FACS-purified α-, β-, and δ-cells using bulk RNA-sequencing have facilitated our understanding complex network cross talk between islet cells its effects on β-cell function. However, these approaches were by design not intended resolve heterogeneity individual cells. Several recent studies used single-cell RNA sequencing (scRNA-Seq) report...
Abstract Aims/hypothesis Type 2 diabetes is characterised by islet amyloid and toxic oligomers of polypeptide (IAPP). We posed the questions, (1) does IAPP toxicity induce an response comparable to that in humans with type diabetes, if so, (2) what are key transcriptional drivers this response? Methods The transcriptome was evaluated five groups mice: beta cell specific transgenic for human IAPP, rodent (3) calpastatin, (4) calpastatin (5) wild-type mice. RNA sequencing data analysed...
Mitochondrial dysfunction plays a central role in type 2 diabetes (T2D); however, the pathogenic mechanisms pancreatic β-cells are incompletely elucidated. Succinate dehydrogenase (SDH) is key mitochondrial enzyme with dual functions tricarboxylic acid cycle and electron transport chain. Using samples from human mouse model of β-cell–specific SDH ablation (SDHBβKO), we define deficiency as driver β-cell failure insulinopenic diabetes. β-Cell impairs glucose-induced respiratory oxidative...
Abstract Background High throughput sequencing has enabled the interrogation of transcriptomic landscape glucagon-secreting alpha cells, insulin-secreting beta and somatostatin-secreting delta cells. These approaches have furthered our understanding expression patterns that define healthy or diseased islet cell types helped explicate some intricacies between major crosstalk glucose regulation. All three endocrine derive from a common pancreatic progenitor, yet cells partially opposing...
Type 2 diabetes (T2D) is associated with compromised identity of insulin-producing pancreatic islet β cells, characterized by inappropriate production other cell-enriched hormones. Here, we examined how hormone misexpression was influenced the MAFA and MAFB transcription factors, closely related proteins that maintain cell function. Mice specifically lacking MafA in cells demonstrated broad, population-wide changes gene expression an overall signature resembling gastrin+ (Gast+) generated...
ABSTRACT Diabetes affects >10% of adults worldwide and is caused by impaired production or response to insulin, resulting in chronic hyperglycemia. Pancreatic islet β-cells are the sole source endogenous insulin our understanding β-cell dysfunction death type 2 diabetes (T2D) incomplete. Single-cell RNA-seq data supports heterogeneity as an important factor function survival. However, it difficult identify which phenotypes critical for T2D etiology progression. Our goal was prioritize...
Abstract While continued cannabis use and misuse in individuals with schizophrenia is associated a variety of negative outcomes, history tend to show higher cognitive performance compared non-users. this replicated the literature, few studies have used task-based functional magnetic resonance imaging (fMRI) evaluate whether brain networks underpinning these features are similarly impacted. Forty-eight first-episode (FES) (FES + CAN), 28 FES no (FES-CAN), 59 controls (CON) performed...
Diabetes affects >10% of adults worldwide and is caused by impaired production or response to insulin, resulting in chronic hyperglycemia. Pancreatic islet β-cells are the sole source endogenous insulin our understanding β-cell dysfunction death type 2 diabetes (T2D) incomplete. Single-cell RNA-seq data supports heterogeneity as an important factor function survival. However, it difficult identify which phenotypes critical for T2D etiology progression. Our goal was prioritize specific...
Diabetes affects >10% of adults worldwide and is caused by impaired production or response to insulin, resulting in chronic hyperglycemia. Pancreatic islet β-cells are the sole source endogenous insulin our understanding β-cell dysfunction death type 2 diabetes (T2D) incomplete. Single-cell RNA-seq data supports heterogeneity as an important factor function survival. However, it difficult identify which phenotypes critical for T2D etiology progression. Our goal was prioritize specific...
Abstract Summary epiRomics is an R package designed to integrate multi-omics data in order identify and visualize enhancer regions alongside gene expression other epigenomic modifications. Regulatory network analysis can be done using combinatory approaches infer of significance such as enhancers, when combining ChIP histone data. Downstream co-occurrence these interest with user-supplied data, chromatin availability or expression. Finally, this allows for results visualized at high...
Islets in humans with T2D, and the brain neurodegenerative disease, share many changes including protein misfolding of amyloidogenic proteins, inflammation, activation vascular endothelium dedifferentiation. Islet amyloid characteristic T2D is derived from IAPP, most aggregate prone toxic known proteins. To address question, does IAPP misfolding-induced stress initiate wide-ranging islets we compared transcriptome human transgenic mice before diabetes onset T2D. Beta cell toxicity reproduces...
<p>Mitochondrial dysfunction plays a central role in Type 2 Diabetes (T2D); however, the pathogenic mechanisms pancreatic β-cells are incompletely elucidated. Succinate dehydrogenase (SDH) is key mitochondrial enzyme with dual functions TCA cycle and electron transport chain (ETC). Using human diabetic samples mouse model of β-cell-specific SDH ablation (SDHBβKO), we define deficiency as driver β-cell failure insulinopenic diabetes. β-Cell impairs glucose-induced respiratory oxidative...
Diabetes is first and foremost a disease of insulin impairment, but often accompanied by aberrant glucagon secretion. Uncontrolled alpha cell activity leads to further complications such as diabetic hyperglycemia, we currently lack good options manage this aspect the disease. Within healthy pancreatic islets, delta cells exert an inhibitory influence over beta via somatostatin; thus, they are uniquely positioned principal source local control preventing hormone signaling from going awry....