A5010160807- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- FOXO transcription factor regulation
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Diabetes Treatment and Management
- Effects of Radiation Exposure
- Genetics and Neurodevelopmental Disorders
- Regulation of Appetite and Obesity
- Metabolism, Diabetes, and Cancer
- Glutathione Transferases and Polymorphisms
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Pediatric Hepatobiliary Diseases and Treatments
- Cardiovascular Effects of Exercise
- Ultrasound and Hyperthermia Applications
- Pancreatitis Pathology and Treatment
- Genetic Associations and Epidemiology
- Management of metastatic bone disease
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Cardiomyopathy and Myosin Studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
Johns Hopkins University
2020-2024
University of Pennsylvania
2007-2023
Johns Hopkins Medicine
2021-2023
Institute of Nutrition, Metabolism and Diabetes
2022
Pancreas Centre (Canada)
2021
VA Tennessee Valley Healthcare System
2014-2015
Vanderbilt University
2011-2015
Vanderbilt University Medical Center
2014
Duke Medical Center
2002-2005
Duke University Hospital
2005
Human pancreatic islets consist of multiple endocrine cell types. To facilitate the detection rare cellular states and uncover population heterogeneity, we performed single-cell RNA sequencing (RNA-seq) on from deceased organ donors, including children, healthy adults, individuals with type 1 or 2 diabetes. We developed a robust computational biology framework for annotation. Using this framework, show that α- β-cells children exhibit less well-defined gene signatures than those in adults....
Background & AimsIntestinal epithelial stem cells that express leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) and/or B cell specific Moloney murine leukemia virus integration site 1 (Bmi1) continuously replicate and generate differentiated throughout life. Previously, Paneth were suggested to constitute an epithelium-intrinsic niche regulates the behavior of these cells. However, ablating has no effect on maintenance functional Here, we show definitively a small subset...
BACKGROUNDMultiple islet autoantibodies (AAbs) predict the development of type 1 diabetes (T1D) and hyperglycemia within 10 years. By contrast, T1D develops in only approximately 15% individuals who are positive for single AAbs (generally against glutamic acid decarboxylase [GADA]); hence, GADA+ state may represent an early stage T1D.METHODSHere, we functionally, histologically, molecularly phenotyped human islets from nondiabetic donors.RESULTSSimilar to few remaining β cells islets, donor...
Targeted gene ablation studies of the endocrine pancreas have long suffered from suboptimal Cre deleter strains. In many cases, lines purportedly specific for beta cells also displayed expression in other islet or a subset neurons brain. Several and experienced silencing mosaicism over time. addition, transgenic constructs were designed to include hGH mini-gene, which by itself increases beta-cell replication decreases function. More recently, driver with CreER inserted into Ins1 locus...
Acute RT-induced damage to the lung is characterized by inflammatory changes, which proceed development of fibrotic lesions in late phase injury. Ultimately, complete structural ablation will ensue, if source inflammatory/fibrogenic mediators and oxidative stress not removed or attenuated. Therefore, purpose this study determine whether overexpression extracellular superoxide dismutase (EC-SOD) mice ameliorates acute radiation induced injury inhibiting activation TGFbeta1 downregulating Smad...
Type 2 diabetes mellitus (T2DM) is characterized by the inability of insulin-producing β-cells to overcome insulin resistance. We previously identified an imprinted region on chromosome 14, DLK1-MEG3 locus, as being downregulated in islets from humans with T2DM. In this study, using targeted epigenetic modifiers, we prove that increased methylation at promoter Meg3 mouse βTC6 results decreased transcription maternal transcripts associated locus. As a result, sensitivity cytokine-mediated...
We tested the hypothesis that targeted transgenic overexpression of human extracellular superoxide dismutase (EC-SOD) would preserve alveolar development in hyperoxia-exposed newborn mice. exposed and wild-type mice to 95% oxygen (O2) or air x 7 days measured bronchoalveolar lavage cell counts, lung homogenate EC-SOD, oxidized reduced glutathione, myeloperoxidase. found total EC-SOD activity was approximately 2.5x activity. Hyperoxia-exposed had less pulmonary neutrophil influx glutathione...
Enzymatic activity of glucokinase was demonstrated, quantitated, and characterized kinetically in rat mouse pituitary extracts using a highly specific sensitive spectrometric assay. A previously proposed hypothesis that the gene might be expressed corticotrophic cells therefore reexamined mRNA situ hybridization immunohistochemical techniques. No evidence found corticotrophs are positive, identity glucokinase-expressing remains to determined. The findings do, however, suggest novel critical...
Type 2 diabetes incidence increases with age, while β-cell replication declines. The transcription factor FoxM1 is required for in various situations, and its expression declines age. We hypothesized that increased activity aged β-cells would rejuvenate proliferation. Induction of an activated form was sufficient to increase mass proliferation 12-month-old male mice after just weeks. Unexpectedly, at months induction improved glucose homeostasis unchanged mass. Cells expressing demonstrated...
Type 1 diabetes (T1D) is an autoimmune disease in which pathogenic lymphocytes target autoantigens expressed pancreatic islets, leading to the destruction of insulin-producing β-cells. Zinc transporter 8 (ZnT8) a major autoantigen abundantly present on β-cell surface. This unique molecular offers potential shield β-cells against attacks T1D. Our previous work showed that monoclonal antibody (mAb43) cell-surface ZnT8 could home islets and prevent autoantibodies from recognizing study...
The forkhead box transcription factor FoxM1, a positive regulator of the cell cycle, is required for β-cell mass expansion postnatally, during pregnancy, and after partial pancreatectomy. Up-regulation full-length however, unable to stimulate increases in unstressed mice or pancreatectomy, probably due lack posttranslational activation. We hypothesized that expression an activated form FoxM1 could aid recovery injury. therefore derived transgenic inducibly express version β-cells...
β-Cell mass is a parameter commonly measured in studies of islet biology and diabetes. However, the rigorous quantification pancreatic β-cell using conventional histological methods time-consuming process. Rapidly evolving virtual slide technology with high-resolution scanners newly developed image analysis tools has potential to transform measurement. To test effectiveness accuracy this new approach, we assessed pancreata from normal C57Bl/6J mice mouse models ablation...
Abstract We investigated the potential role of sleep-trait associated genetic loci in conferring a degree their effect via pancreatic α- and β-cells, given that both sleep disturbances metabolic disorders, including type 2 diabetes obesity, involve polygenic contributions complex interactions. determined commonalities between conducting linkage disequilibrium correlation analyses with publicly available GWAS summary statistics. Then we possible enrichment SNPs promoter-interacting open...
Abstract A three‐step model for myofibrillogenesis has been proposed the formation of myofibrils [Rhee et al., 1994 : Cell Motil. Cytoskeleton 28:1–24; Sanger 2002 Adv. Exp. Med. 481:89–105]: premyofibril to nascent myofibril mature myofibril. We have found two chemically related inhibitors that will arrest development at both first and second step. Cultured quail embryonic skeletal myoblasts were treated with ethyl methane sulfonate (EMS) or 2‐aminoethyl‐methanesulfonate (MTSEA + ). When...
Abstract Type 1 diabetes (T1D) is an autoimmune disease of only partially defined etiology in which immune cells destroy insulin-producing beta cells. Using single-cell transcriptomics and advanced analytical strategy to assess pancreatic islets T1D, autoantibody-positive, non-diabetic organ donors, we identified both canonical cell types rare insulin-expressing with a hybrid mixture endocrine exocrine gene signatures within all donors. We further found elevated expression MHC Class II...