grant
Novel Roles of TAZ and YAP in DNA Damage Repair with 3D Genome Organization and the Therapeutic Resistance in Glioblastoma
Organization MAYO CLINIC ARIZONALocation SCOTTSDALE, UNITED STATESPosted 3 Jun 2024Deadline 31 May 2028
NIHUS FederalResearch GrantFY202521+ years old3-D3-Dimensional3DAP-1AP-1 Enhancer-Binding ProteinAP1AP1 proteinActivator Protein-1AdultAdult HumanAffectAggressionAggressive behaviorAmericanArchitectureAssayBPD verteporfinBPD-MABasal Transcription FactorBasal transcription factor genesBenzoporphyrin Derivative Monoacid Ring ABindingBioassayBiochemicalBiologicalBiological AssayBiologyBrain CancerBrain NeoplasiaBrain NeoplasmsBrain TumorsCRISPRCRISPR/Cas systemCatalytic CoreCatalytic DomainCatalytic RegionCatalytic SiteCatalytic SubunitCell BodyCellsChIP SequencingChIP-seqChIPseqChromatinChromatin StructureClinical TrialsClustered Regularly Interspaced Short Palindromic RepeatsComplexCytotoxic ChemotherapyCytotoxic TherapyDNADNA DamageDNA Damage RepairDNA Double Strand BreakDNA InjuryDNA Molecular BiologyDNA RepairDNA lesionDNA- PKcs proteinDNA-Activated Protein Kinase Catalytic SubunitDNA-PKDNA-activated protein kinaseDNA-dependent protein kinaseDNA-dependent protein serine-threonine kinaseDataDeoxyribonucleic AcidDevelopmentDiseaseDisorderDouble Strand Break RepairEngineering / ArchitectureEnhancer-Binding Protein AP1EnhancersGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGeneralized GrowthGenesGenetic TranscriptionGenomeGlial Cell TumorsGlial NeoplasmGlial TumorGlioblastomaGliomaGrade IV Astrocytic NeoplasmGrade IV Astrocytic TumorGrade IV AstrocytomaGrowthHeterochromatinHeterograftHeterologous TransplantationHi-CHyper-Radiosensitivity Of Murine SCID Mutation, Complementing 1In VitroIonizing Electromagnetic RadiationIonizing radiationKineticsKnowledgeKu Antigen, 80-kD SubunitKu80Ku86L-SerineL-ThreonineMalignant Tumor of the BrainMalignant neoplasm of brainMediatingMesenchymalMiceMice MammalsMolecularMolecular BiologyMolecular InteractionMurineMusNHEJNecrosisNecroticNeighborhoodsNerve CellsNerve UnitNeural CellNeurocyteNeuroglial NeoplasmNeuroglial TumorNeuronal DifferentiationNeuronsNon-Homologous End JoiningNon-homologous DNA End JoiningNonhomologous DNA End JoiningNonhomologous End JoiningNuclear TranslocationOncogenicOutcomePRO-seqPathway interactionsPatientsPhosphorylationPlayPre-Clinical ModelPrecision Run-On SequencingPrecision nuclear run-on sequencingPreclinical ModelsProtein PhosphorylationProteinsRNA ExpressionRadiation therapyRadiation-Ionizing TotalRadioresistanceRadiosensitizationRadiotherapeuticsRadiotherapyRecurrent NeoplasmRecurrent tumorReducing AgentsReductantsReporterResistanceRoleSCID proteinScaffolding ProteinSerineSiteStructureSurvival AnalysesSurvival AnalysisTechnologyTestingTherapeuticThreonineTissue GrowthTranscriptionTranscription Factor AP-1Transcription Factor Proto-OncogeneTranscription factor genesUnscheduled DNA SynthesisVerteporfinVisudyneX-Ray Repair, Complementing Defective, In Chinese Hamster, 5XRCC5XRCC5 geneXRCC7 proteinXenograftXenograft procedureXenotransplantationadulthoodbenzoporphyrin Dbiologiccancer clinical trialcancer progressioncancer typecheck point blockadecheckpoint blockadechemo-/radio-sensitizationchromatin immunoprecipitation coupled with sequencingchromatin immunoprecipitation followed by sequencingchromatin immunoprecipitation with sequencingchromatin immunoprecipitation-seqchromatin immunoprecipitation-sequencingclinical relevanceclinically relevantcofactorcohesincohesionconfocal imagingdevelopmentalepigenomicsglial-derived tumorglioblastoma multiformeglioma cancer stem cellglioma cancer stem like cellglioma progenitorglioma stem cellsglioma stem like cellimmune check point blockadeimmune checkpoint blockadeimprovedin vitro Assayin vivoinhibitorionizing outputirradiationmouse modelmurine modelneoplasm progressionneoplasm recurrenceneoplastic progressionneuroglia neoplasmneuroglia tumorneuronalnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generationnext generation therapeuticsnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapyoncology clinical trialontogenyoverexpressoverexpressionp460 proteinparalogparalogous genepathwaypharmacologicprogramsprotein complexradiation resistanceradiation sensitizationradiation treatmentradio resistanceradio-/chemo-sensitizationradio-sensitizationradiotherapy sensitizationrecruitresistance to therapyresistantresistant to therapyresponsesocial rolespongioblastoma multiformestemtargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic resistancetherapeutic targettherapy resistantthree dimensionaltranscription factortransdifferentiationtreatment resistancetreatment with radiationtumor ablationtumor growthtumor progressiontumors in the brainverteporphinxeno-transplantxeno-transplantation
Description preview
PROJECT SUMMARY
Glioblastoma (GBM) is an aggressive type of brain cancer that arises de novo and is therapy resistant. A key
contributor to poor outcomes in GBM is a subpopulation of cells called glioma stem-like cells (GSCs) that evade
conventional cytotoxic therapies and repopulate as recurrent tumors. A fuller understanding of the molecular…
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