grant
Brain microenviornment-dependent lineage plasticity drives adaptation to targeted therapy in malignant gliomas
Organization UNIVERSITY OF CALIFORNIA LOS ANGELESLocation LOS ANGELES, UNITED STATESPosted 1 Jul 2024Deadline 30 Jun 2028
NIHUS FederalResearch GrantFY202521+ years oldAblationAdultAdult HumanAffectAmericanAstrocytesAstrocytusAstrogliaAutomobile DrivingB-raf KinasesB-raf-1BRAFBRAF KinasesBRAF geneBar CodesBrainBrain CancerBrain NeoplasiaBrain NeoplasmsBrain Nervous SystemBrain TumorsCancer GenesCancer-Promoting GeneCancersCell BodyCell Communication and SignalingCell FunctionCell PhysiologyCell ProcessCell SignalingCellsCellular FunctionCellular PhysiologyCellular ProcessClinicalCombined Modality TherapyComplexCoupledCytotoxic ChemotherapyCytotoxic TherapyDNA TherapyDNA mutationDataDevelopmentDiseaseDisease ProgressionDisorderDown-RegulationDrug TargetingDrug TherapyDrug resistanceDrugsEGF ReceptorEGFRERBB ProteinEncephalonEnvironmentEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor KinaseEpidermal Growth Factor Receptor Protein-Tyrosine KinaseEpidermal Growth Factor-Urogastrone ReceptorsEvolutionExtracellular Signal-Regulated Kinase GeneGene ExpressionGene TranscriptionGene Transfer ClinicalGeneticGenetic ChangeGenetic InterventionGenetic TranscriptionGenetic defectGenetic mutationGliaGlial Cell TumorsGlial CellsGlial NeoplasmGlial TumorGlioblastomaGliomaGoalsGrade IV Astrocytic NeoplasmGrade IV Astrocytic TumorGrade IV AstrocytomaHER1HeterogeneityHeterograftHeterologous TransplantationHumanIn VitroIndividualIntracellular Communication and SignalingIntratumoral heterogeneityKolliker's reticulumLineage TracingLinkMAP Kinase GeneMAPKMalignantMalignant - descriptorMalignant CellMalignant Glial NeoplasmMalignant Glial TumorMalignant GliomaMalignant NeoplasmsMalignant Neuroglial NeoplasmMalignant Neuroglial TumorMalignant TumorMalignant Tumor of the BrainMalignant neoplasm of brainMediatingMedicationMitogen-Activated Protein Kinase GeneModelingModern ManMolecularMultimodal TherapyMultimodal TreatmentMultipotent Stem CellsMutateMutationNPCNerve CellsNerve UnitNeural CellNeural DevelopmentNeural Stem CellNeurocyteNeurogliaNeuroglial CellsNeuroglial NeoplasmNeuroglial TumorNeuronsNon-neuronal cellNonneuronal cellNuclear Pore ComplexOligodendrocytesOligodendrocytusOligodendrogliaOligodendroglia CellOncogenesOncogenicOrganoidsPDX modelPatient derived xenograftPatientsPharmaceutical PreparationsPharmacological TreatmentPharmacotherapyPhenotypePlayPre-Clinical ModelPreclinical ModelsProcessProgenitor CellsProliferatingProtein-Serine KinaseProtein-Serine-Threonine KinasesProtein-Threonine KinaseProteomicsProto-Oncogene Proteins B-rafRAFB1RNA ExpressionRadialRadiusReceptor InhibitionReceptor SignalingRegulationReporterResistanceResolutionRoleSerine KinaseSerine-Threonine KinasesSerine/Threonine Protein Kinase GeneSignal PathwaySignal TransductionSignal Transduction SystemsSignalingStem Cell likeSubcellular ProcessSystemTGF-alpha ReceptorTechniquesTherapeuticTherapeutic InterventionThreonine KinaseTranscriptionTransforming GenesTransforming Growth Factor alpha ReceptorTumor CellUrogastrone ReceptorWorkXenograftXenograft procedureXenotransplantationadulthoodastrocytic gliabarcodebiological signal transductionc-erbB-1c-erbB-1 Proteincancer cellcell lineage analysiscell lineage mappingcell lineage tracingcell lineage trackingcellular lineage mappingcellular lineage trackingclinical developmentcohortcombination therapycombined modality treatmentcombined treatmentdevelopmentaldrivingdrug interventiondrug resistantdrug treatmentdrug/agenterbB-1erbB-1 Proto-Oncogene ProteinerbBlgene repair therapygene therapygene-based therapygenetic therapygenome mutationgenomic therapyglial-derived tumorglioblastoma multiformeheterogeneity in tumorsin vitro Modelindividualized therapeuticinnovateinnovationinnovativeinsightintervention therapyintra-tumoral heterogeneityintratumor heterogeneitymalignancymolecular targeted therapeuticsmolecular targeted therapiesmolecular targeted treatmentmulti-modal therapymulti-modal treatmentmultipotent progenitormultipotent progenitor cellneoplasm/cancerneoplastic cellnerve cementnerve stem cellneuralneural precursorneural precursor cellneural progenitorneural progenitor cellsneural stem and progenitor cellsneurodevelopmentneurogenic progenitorsneurogenic stem cellneuroglia neoplasmneuroglia tumorneuron progenitorsneuronalneuronal progenitorneuronal progenitor cellsneuronal stem cellsneuroprogenitornon-geneticnongeneticnoveloligodendrocyte precursoroligodendrocyte precursor celloligodendrocyte progenitoroligodendrocyte stem cellpatient derived xenograft modelpediatric low grade gliomapersonalized therapeuticpharmaceutical interventionpharmacologicpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticspre-clinicalpreclinicalpressureprogenitorprogenitor and neural stem cellsprogenitor capacityprogenitor cell likeprogenitor-likeprogramsproto-oncogene protein c-erbB-1rational designreceptor expressionresistance to Drugresistance to therapyresistantresistant to Drugresistant to therapyresolutionsresponsescRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial rolespongioblastoma multiformestem cell characteristicsstem cellsstem-likestemnesssubcutaneoussubdermalsuccesstargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic resistancetherapy resistanttranscriptomicstreatment resistancetreatment strategytumortumor heterogeneitytumor initiationtumors in the brainv-raf Murine Sarcoma Viral Oncogene Homolog B1xeno-transplantxeno-transplantation
Description preview
PROJECT SUMMARY/ABSTRACT
Malignant gliomas are the most common primary adult brain cancer, affecting over 20,000 Americans each year.
While molecularly targeted therapies have demonstrated tremendous successes in other malignancies, there is
a lack of effective and personalized therapeutic approaches for these deadly brain cancers. The goal of…
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