grant
Analyzing DNA replication and damage vulnerability in IDH mutant glioma
Organization MASSACHUSETTS GENERAL HOSPITALLocation BOSTON, UNITED STATESPosted 1 Mar 2024Deadline 28 Feb 2029
NIHUS FederalResearch GrantFY202621+ years oldAccelerationAdenosine 5'-(trihydrogen diphosphate), P'-5-ester with D-ribose, homopolymerAdultAdult HumanAfter CareAfter-TreatmentAftercareAlkylating AgentsAlkylatorsAutomobile DrivingBRCA1BRCA1 Gene ProductBRCA1 ProteinBRCA1 geneBreast Cancer 1 GeneBreast Cancer 1 Gene ProductBreast Cancer Type 1 Susceptibility GeneBreast Cancer Type 1 Susceptibility ProteinBreast-Ovarian Cancer ProteinCancersCaspaseCaspase GeneCausalityCell BodyCell Communication and SignalingCell DeathCell Death SignalingCell Death Signaling ProcessCell SignalingCell-Death ProteaseCellsClinicClinicalClinical TreatmentCombined Modality TherapyConsumptionCysteine EndopeptidasesCysteine ProteaseCysteine ProteinasesDNA AlterationDNA DamageDNA InjuryDNA ReplicationDNA Sequence AlterationDNA SynthesisDNA analysisDNA biosynthesisDNA dependent protein kinase catalytic subunitDNA mutationDNA replication forkDNA- PKcs proteinDNA-Activated Protein Kinase Catalytic SubunitDNA-PKDNA-PKcsDNA-activated protein kinaseDNA-dependent protein kinaseDNA-dependent protein serine-threonine kinaseDependenceDiffuseDihydronicotinamide Adenine DinucleotideDiphosphopyridine NucleotideDoseEarly Onset Gene Breast Cancer 1Early Onset Protein Breast Cancer 1Enzyme GeneEnzymesEtiologyGenesGeneticGenetic AlterationGenetic ChangeGenetic defectGenetic mutationGlial Cell TumorsGlial NeoplasmGlial TumorGliomaGlycohydrolasesGlycosidasesGlycoside HydrolasesGoalsHematologyHereditary Breast Cancer 1Hyper-Radiosensitivity Of Murine SCID Mutation, Complementing 1ICE-like proteaseIntermediary MetabolismIntracellular Communication and SignalingInvestigationIonizing Electromagnetic RadiationIonizing radiationIsocitrate DehydrogenaseKnowledgeLaboratoriesLinkLytotoxicityMalignant CellMalignant Glial NeoplasmMalignant Glial TumorMalignant GliomaMalignant NeoplasmsMalignant Neuroglial NeoplasmMalignant Neuroglial TumorMalignant TumorMediatingMediatorMetabolicMetabolic ProcessesMetabolismMissionModalityModelingMolecularMultimodal TherapyMultimodal TreatmentMutationNadideNatural HistoryNeuroglial NeoplasmNeuroglial TumorNicotinamide adenine dinucleotideNicotinamide-Adenine DinucleotideNormal CellPARP InhibitorPARP PolymerasePARP proteinPARP-1 inhibitorPARPiPARSPathway interactionsPatientsPhenotypePoly Adenosine Diphosphate RibosePoly(ADP-ribose) Polymerase InhibitorPoly(ADP-ribose) PolymerasesPoly(ADP-ribose) polymerase 1 inhibitorPoly(ADPribose) PolymerasePoly-ADPRPolymerasePolymersPre-Clinical ModelPreclinical ModelsPredispositionPublic HealthRNF53RadiationRadiation therapyRadiation-Ionizing TotalRadiotherapeuticsRadiotherapyResearchRoleSCID proteinSequence AlterationSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSupplementationSusceptibilityTemodalTemodarTestingTherapeuticTherapeutic EffectToxic effectToxicitiesTranslationsTumor CellWorkX-Ray Repair, Complementing Defective, in Chinese Hamster, 1XRCC1XRCC1 geneXRCC7 proteinadult youthadulthoodaggressive therapyaggressive treatmentanalyze DNAbiological adaptation to stressbiological signal transductionbrca 1 genecancer cellcausationclinical developmentclinical interventionclinical therapyclinical translationclinically translatablecombination therapycombinatorialcombined modality treatmentcombined treatmentcystein proteasecystein proteinasecysteine endopeptidasecytotoxicitydetermine efficacydisease causationdrivingefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationevaluate efficacyexamine efficacygenome mutationgenomic alterationgenotoxicityglial-derived tumorhomologous recombination deficiencyhomologous recombination repair deficiencyimprovedin vitro Modelin vivoinhibitorinnovateinnovationinnovativeionizing outputmalignancymethazolastonemulti-modal therapymulti-modal treatmentmutantnecrocytosisneoplasm/cancerneoplastic cellneuroglia neoplasmneuroglia tumornew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynovelnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachp460 proteinpathwaypharmacologicpoly (ADP-ribose)poly ADP polymerasepoly ADP ribose synthetasepolymerpolymericpost treatmentradiation effectradiation treatmentreaction; crisisrecruitreplication forkreplication stressresponsesocial rolestandard carestandard treatmentstress responsestress; reactionsynthetic lethal interactionsynthetic lethalitysystemic toxicitytemozolomidetranslationtreatment with radiationtrial regimentrial treatmenttumoryoung adultyoung adult ageyoung adulthood
Description preview
Project Summary
Adult diffuse gliomas that harbor mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are
common in younger adults, and universally evade the current aggressive therapies and remain lethal. Our team
led by Co-PIs Drs. Cahill and Wakimoto have identified unique metabolic dependencies and combinatorial
therapeutic…
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