grant
Epigenomic mechanisms of cardiac fibrosis and heart failure
Organization J. DAVID GLADSTONE INSTITUTESLocation SAN FRANCISCO, UNITED STATESPosted 12 Sept 2025Deadline 31 May 2029
NIHUS FederalResearch GrantFY2025AffectArchitectureAutomobile DrivingBET bromodomain inhibitorBET inhibitorBETiBasal Transcription FactorBasal transcription factor genesBeta Proprotein Interleukin 1BiP geneBiP proteinBindingBlood VesselsBody TissuesBone-Derived Transforming Growth FactorBromodomainBromodomain and Extra-Terminal motif inhibitorBromodomains and extra-terminal domain inhibitorCRISPR interferenceCRISPR-dCas9-mediated repressionCRISPR/dCas9 interferenceCRISPR/dCas9-mediated transcriptional inhibitionCRISPRiCardiacCardiac Muscle CellsCardiac MyocytesCardiocyteCell BodyCell Communication and SignalingCell Growth in NumberCell LineCell MultiplicationCell ProliferationCell SignalingCell-Extracellular MatrixCellLineCellsCellular ProliferationChromatinChromosome MappingChronicChronic DiseaseChronic IllnessClinicalClustered Regularly Interspaced Short Palindromic Repeats interferenceCre driverDNADataData SetDeoxyribonucleic AcidDevelopmentDiagnosisDiseaseDisease ProgressionDisorderDistalECMElementsEngineering / ArchitectureEnhancersExtracellular MatrixFibroblastsFibrosisFibrosis in the heartFibrosis in the myocardiumFibrosis within the heartFibrosis within the myocardiumFibrotic myocardiumGRP78GRP78 geneGene LocalizationGene MappingGene Mapping GeneticsGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGenesGeneticGenetic TranscriptionGerm LinesGlucose-Regulated Protein, 78-kDGoalsHSPA5HeartHeart Muscle CellsHeart failureHeart myocyteHeat-Shock 70-kD Protein 5HistonesHumanIL-1 betaIL-1 βIL-1-bIL-1βIL1-BetaIL1-βIL1B ProteinIL1F2IL1βImmuneImmunesIn VitroInflammatoryIntegrinsIntegrins Extracellular MatrixInterleukin 1betaInterleukin-1 betaInterleukin-1βIntracellular Communication and SignalingKnowledgeLinkLinkage MappingMapsMediatorMethodsMiceMice MammalsMilk Growth FactorModelingModern ManMolecularMolecular InteractionMorbidityMorbidity - disease rateMurineMusMyocardial depressionMyocardial dysfunctionNucleic Acid Regulator RegionsNucleic Acid Regulatory SequencesOutcomePathogenesisPathologicPatientsPeptide DomainPlatelet Transforming Growth FactorPreinterleukin 1 BetaPreventiveProtein DomainsProteinsQOLQuality of lifeRNA ExpressionRegulationRegulator GenesRegulatory ElementRegulatory RegionsRepressionResearchRoleSeverity of illnessSignal PathwaySignal TransductionSignal Transduction SystemsSignalingStrains Cell LinesStressTGF BTGF-betaTGF-βTGFbetaTGFβTertiary Protein StructureTestingTimeTissuesTotal Human and Non-Human Gene MappingTranscriptionTranscription Factor Proto-OncogeneTranscription factor genesTranscriptional Regulatory ElementsTransforming Growth Factor betaTransforming Growth Factor-Beta Family GeneUpregulationaorta constrictionbiological signal transductionbromodomain extra-terminal inhibitorcardiac dysfunctioncardiac failurecardiac fibrosiscardiac functioncardiomyocytecell typechronic disordercoronary fibrosiscultured cell linedevelopmentaldisease severitydrivingepigenomicsfibrotic heartfunction of the heartgene networkgene regulatory networkgenetic mappinggenetic regulatory elementgenetic trans acting elementgenome scalegenome-widegenomewideheart dysfunctionheart fibrosisheart functionhiPSChistone modificationhuman diseasehuman iPShuman iPSChuman induced pluripotent cellhuman induced pluripotent stem cellshuman inducible pluripotent stem cellshuman inducible stem cellsimmunoglobulin heavy chain-binding proteinimprovedin vivoinduced human pluripotent stem cellsinnovateinnovationinnovativeinsightmortalitymouse modelmurine modelmyocardial fibrosisnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynovelnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachpharmacologicprogramsregulatory generepressing CRISPR-dCas9 systemsingle cell analysissingle cell genomicssmall moleculesocial rolestandard of caretargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic targettooltrans acting elementtranscription factortranscriptomicsvascular
Description preview
PROJECT SUMMARY
A heart failure diagnosis leads to poor quality of life and a 5-year mortality nearing 50%, underscoring the urgent
need for innovative treatments. Clinical evidence strongly links myocardial fibrosis, driven by pathological
activation of cardiac fibroblasts, with unfavorable outcomes in heart failure patients. Prior efforts to…
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