grant
The role of EZH1 in neuronal differentiation and neurological disorders
Organization CHILDREN'S HOSP OF PHILADELPHIALocation PHILADELPHIA, UNITED STATESPosted 5 May 2022Deadline 30 Apr 2027
NIHUS FederalResearch GrantFY20260-11 years old21+ years oldActivator AppliancesActivator Orthodontic AppliancesAdultAdult HumanAutoregulationBehavioralBindingBiologic ModelsBiological ModelsCell BodyCell LineCell NucleusCellLineCellsCerebral cortexChildChild YouthChildren (0-21)ChromatinChromatin Remodeling ComplexChromatin Remodeling FactorCognitiveComplexDNA mutationDataDate of birthDefectDevelopmentDevelopmental ProcessDifferential Gene ExpressionDifferentiated GeneDiseaseDisorderDysfunctionEC 2.1.1ENX-1ES cell differentiationESC differentiationEZH1EZH2EZH2 geneEnhancer of Zeste 2 Polycomb Repressive Complex 2 SubunitEnhancersEnzyme GeneEnzymesEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessFore-BrainForebrainFunction ActivatorFunctional disorderGene Down-RegulationGeneHomologGenetic ChangeGenetic EngineeringGenetic Engineering BiotechnologyGenetic Engineering Molecular BiologyGenetic defectGenetic mutationGenetic studyGenomicsGoalsHistonesHomeostasisHomologHomologous GeneHomologueHumanImmunoblottingIntellectual disabilityIntellectual functioning disabilityIntellectual limitationKMT6KMT6AKnock-outKnockoutKnowledgeL-LysineLaboratoriesLifelong disabilityLysineMaintenanceMeasuresMediatingMethylationMethyltransferaseModel SystemModern ManMolecularMolecular InteractionMorphologyMutationNerve CellsNerve UnitNervous SystemNervous System DiseasesNervous System DisorderNeural CellNeural DevelopmentNeural Stem CellNeuritesNeurobiologyNeurocyteNeurodevelopmental DisorderNeurologic Body SystemNeurologic DisordersNeurologic Organ SystemNeurological Development DisorderNeurological DisordersNeuronal DifferentiationNeuronsNucleusOrganoidsPathogenesisPathogenicityPatientsPermanent disabilityPhysiological HomeostasisPhysiopathologyPolycombProsencephalonProtocolProtocols documentationRNA SeqRNA sequencingRNAseqRecombinant DNA TechnologyRegulationRoleStrains Cell LinesSyndromeTechnologyTestingTimeTissue-Specific Differential Gene ExpressionTissue-Specific Gene ExpressionTranscription ActivationTranscription ActivatorTranscription CoactivatorTranscription Factor CoactivatorTranscription RepressionTranscriptional ActivationTranscriptional Activator/CoactivatorTranscriptional ControlTranscriptional RegulationUpregulationWestern BlottingWestern ImmunoblottingWorkadulthoodbrain atrophycell typecerebral atrophychromatin modifiercompare to controlcomparison controlcortical atrophycultured cell linedesigndesigningdevelopmentaldifferentiation in embryonic stem cellsembryonic precursor differentiationembryonic stem cell differentiationepigeneticallyexperimentexperimental researchexperimental studyexperimentsgain of functiongain of function mutationgene repressiongenetically engineeredgenome mutationhESChuman ES cellhuman ESChuman embryonic stem cellinhibitorinsightintellectual and developmental disabilitykidslimited intellectual functioningloss of functionloss of function mutationmethylasemonolayermutantnerve stem cellnervous system developmentneural precursorneural precursor cellneural progenitorneural progenitor cellsneural stem and progenitor cellsneurobiologicalneurodevelopmentneurodevelopmental diseaseneurogenesisneurogenic progenitorsneurogenic stem cellneurological diseaseneuron progenitorsneuronalneuronal progenitorneuronal progenitor cellsneuronal stem cellsneuroprogenitornew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetpathophysiologypostmitoticprematureprematuritypreservationprogenitor and neural stem cellsprogenitor cell fate specificationprogenitor cell markersprogenitor cell proliferationprogenitor fate specificationprogenitor markersprogenitor proliferationprogenitor specificationprogenitor stem cell markersprotein blottingrecruitscRNA sequencingscRNA-seqself organizationsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial rolestem and progenitor cell proliferationstem cell biomarkersstem cell fate specificationstem cell markersstem cell proliferationstem cell specificationtranscriptome sequencingtranscriptomic sequencingtransmethylaseyoungster
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PROJECT SUMMARY
Intellectual disabilities (ID) are lifelong conditions caused by neurodevelopmental errors. We recently identified
gain and loss of function (GOF and LOF) mutations in the chromatin modifier Enhancer of Zeste Homologue 1
(EZH1) as the cause a previously undiagnosed intellectual disability syndrome in ten children. EZH1 is one of…
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