Synthesis and Biological Validation of a Harmine-based, Central Nervous System (CNS)-Avoidant, Selective, Human β-Cell Regenerative Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) Inhibitor

Consortia: CTAR

Kumar K, Wang P, Wilson J, Zlatanic V, Berrouet C, Khamrui S, Secor C, Swartz E, Lazarus MB, Sanchez R, Stewart AF, Garcia-Ocana A, DeVita RJ.
J Med Chem. 2020 Jan 31. doi: 10.1021/acs.jmedchem.9b01379. PMID:32003560

All Intrinsically disordered domain of transcription factor TCF-1 is required for T cell developmental fidelity Alpha cell receptor for advanced glycation end products associate with glucagon expression in type 1 diabetes SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells m 6 A mRNA Methylation Regulates Early Pancreatic β-Cell Differentiation Pericyte dysfunction and impaired vasomotion are hallmarks of islets during the pathogenesis of type 1 diabetes Protein disorder in the regulatory control of mitophagy Human immune phenotyping reveals accelerated aging in type 1 diabetes Stromal Interaction Molecule 1 Maintains β Cell Identity and Function in Female Mice through Preservation of G Protein-Coupled Estrogen Receptor 1 Signaling The pathogenic “symphony” in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas Inferring regulators of cell identity in the human adult pancreas Generation of the NeoThy mouse model for human immune system studies GLP-1R agonists demonstrate potential to treat Wolfram syndrome in human preclinical models Plasma protein biomarkers predict the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity Protocol to generate and utilize pancreatic tissue slices to study endocrine and exocrine physiology in situ from mouse and human tissue Major β cell-specific functions of NKX2.2 are mediated via the NK2-specific domain Human circulating and tissue-resident memory CD8(+) T cells Universal open MHC-I molecules for rapid peptide loading and enhanced complex stability across HLA allotypes Pancreatic regional blood flow links the endocrine and exocrine diseases Excess pancreatic elastase alters acinar-β cell communication by impairing the mechano-signaling and the PAR2 pathways Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response Analysis of a macrophage carbamylated proteome reveals a function in post-translational modification crosstalk Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing Title: β Cell microRNAs Function as Molecular Hubs of Type 1 Diabetes Pathogenesis and as Biomarkers of Diabetes Risk Enrichment of stem cell-derived pancreatic beta-like cells and controlled graft size through pharmacological removal of proliferating cells Acrylic-based culture plate format perfusion device to establish liver endothelial-epithelial interface cytoviewer: an R/Bioconductor package for interactive visualization and exploration of highly multiplexed imaging data m (6) A mRNA Methylation in Brown Adipose Tissue Regulates Systemic Insulin Sensitivity via an Inter-Organ Prostaglandin Signaling Axis Mapping genetic effects on cell type-specific chromatin accessibility and annotating complex immune trait variants using single nucleus ATAC-seq in peripheral blood Immune engineered extracellular vesicles to modulate T cell activation in the context of type 1 diabetes Simultaneous evaluation of treatment efficacy and toxicity for bispecific T-cell engager therapeutics in a humanized mouse model Quantitative control of Ets1 dosage by a multi-enhancer hub promotes Th1 cell differentiation and protects from allergic inflammation Immunotherapy With Low-Dose IL-2/CD25 Prevents β-Cell Dysfunction and Dysglycemia in Prediabetic NOD Mice Modeling cell-mediated immunity in human type 1 diabetes by engineering autoreactive CD8(+) T cells A genomic data archive from the Network for Pancreatic Organ donors with Diabetes Integrating genetics with single-cell multiomic measurements across disease states identifies mechanisms of beta cell dysfunction in type 2 diabetes Senescence: a double-edged sword in beta-cell health and failure? Functional interrogation of twenty type 2 diabetes-associated genes using isogenic hESC-derived β-like cells β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT Strong ubiquitous micro-promoters for recombinant adeno-associated viral vectors Extrahepatic transplantation of 3D cultured stem cell-derived islet organoids on microporous scaffolds Single-cell expression profiling of islets generated by the Human Pancreas Analysis Program Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue Interpreting non-coding disease-associated human variants using single-cell epigenomics Human pluripotent-stem-cell-derived organoids for drug discovery and evaluation Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes Rediscovering Primary Cilia in Pancreatic Islets The human α cell in health and disease Stomach-derived human insulin-secreting organoids restore glucose homeostasis Deletion of the Unfolded Protein Response Transducer IRE1α Is Detrimental to Aging Photoreceptors and to ER Stress-Mediated Retinal Degeneration Ca(2+) Release or Ca(2+) Entry, that is the Question: What Governs Ca(2+) Oscillations in Pancreatic Beta Cells?
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