grant
Neuro-immune mechanisms in mutant IDH1 gliomas
Organization UNIVERSITY OF MICHIGAN AT ANN ARBORLocation ANN ARBOR, UNITED STATESPosted 1 Aug 2025Deadline 30 Jun 2029
NIHUS FederalResearch GrantFY20252-ketoglutarate2-oxoglutarate21+ years oldActive SitesAdultAdult HumanAffectAggressionAggressive behaviorAntigen ReceptorsAstrocytic GliomaAstrocytic NeoplasmAstrocytic TumorAstrocytomaAstrogliomaBone MarrowBone Marrow Reticuloendothelial SystemCell BodyCell DifferentiationCell Differentiation processCell IsolationCell LocomotionCell MigrationCell MovementCell SegregationCell SeparationCell Separation TechnologyCellsCellular MigrationCellular MotilityClassificationCombination immunotherapyDNADNA DamageDNA InjuryDNA TherapyDNA mutationDataData AnalysesData AnalysisDeoxyribonucleic AcidDevelopmentDioxygenasesDysfunctionEnzyme GeneEnzymesEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEventExhibitsFunctional disorderGEM modelGEMM modelGene Transfer ClinicalGene set enrichment analysisGeneralized GrowthGeneticGenetic ChangeGenetic EngineeringGenetic Engineering BiotechnologyGenetic Engineering Molecular BiologyGenetic InterventionGenetic defectGenetic mutationGenetically Engineered MouseGenomic DNAGlial Cell TumorsGlial NeoplasmGlial TumorGliomaGliomagenesisGoalsGrowthHistonesHumanHypermethylationImmuneImmune mediated therapyImmune memoryImmune responseImmune systemImmunesImmunityImmunocompetentImmunologic MemoryImmunological MemoryImmunologically Directed TherapyImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyIntracranial Central Nervous System NeoplasmsIntracranial Central Nervous System TumorsIntracranial NeoplasmsIntracranial TumorIsocitrate DehydrogenaseL-LysineLeadLesionLymphatic cellLymphocyteLymphocyticLysineMediatingMetabolicMethylationMiceMice MammalsModelingModern ManMolecular FingerprintingMolecular ProfilingMurineMusMutationMyelogenousMyeloidMyeloid CellsNeighborhoodsNeural Stem CellNeuroglial NeoplasmNeuroglial TumorNeuroimmune MechanismsNeuroimmune ProcessesNeuroimmunomodulationPathway interactionsPatientsPb elementPhenotypePhysiopathologyPlayProductionPrognosisPropertyRNA SeqRNA sequencingRNAseqReceptor ActivationRecombinant DNA TechnologyRecurrenceRecurrentRegulationSamplingSignal PathwaySleeping BeautySystemSystematicsTherapeuticTherapeutic InterventionTissue GrowthTransposaseTreatment EfficacyTumor-infiltrating immune cellsadulthoodalpha ketoglutarateanamnestic reactioncancer microenvironmentcell motilitycell sortingcellular differentiationcombination gene therapycombinatorial immunotherapycytokinedata interpretationdemethylationdevelopmentaldual immunotherapyepigeneticallygDNAgain of functiongene functiongene repair therapygene therapygene-based therapygenetic therapygenetically engineeredgenetically engineered mouse modelgenetically engineered murine modelgenome mutationgenomic therapyglial-derived tumorglioma genesisglobal gene expressionglobal transcription profileheavy metal Pbheavy metal leadhost responseimmune cell infiltration of tumorsimmune cells infiltrating the tumorimmune cells that infiltrate the tumorimmune competentimmune microenvironmentimmune suppressionimmune suppressive activityimmune suppressive functionimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunoneurologyimmunoresponseimmunosuppressive activityimmunosuppressive functionimmunosuppressive microenvironmentimmunosuppressive responseimmunosuppressive tumor microenvironmentin vivoinfiltration of tumors by immune cellsinhibitorintervention efficacyintervention therapyintratumoral immune cellintratumoral immune infiltratelymph cellmolecular profilemolecular signaturemutantnerve stem cellneural precursorneural precursor cellneural progenitorneural progenitor cellsneural stem and progenitor cellsneurogenic progenitorsneurogenic stem cellneuroglia neoplasmneuroglia tumorneuroimmunologyneuron progenitorsneuronal progenitorneuronal progenitor cellsneuronal stem cellsneuroprogenitorontogenypathophysiologypathwayprogenitor and neural stem cellsrecruitresponsescATAC sequencingscATAC-seqscRNA sequencingscRNA-seqsecondary immune responsesingle cell ATAC-seqsingle cell ATAC-sequencingsingle cell Assay for Transposase Accessible Chromatin sequencingsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell sequencing assay for transposase accessible chromatinsingle cell transcriptomic profilingsingle-cell Assay for Transposase-Accessible Chromatin with sequencingsingle-cell RNA sequencingsingle-cell assay for transposase-accessible chromatin using sequencingsingle-cell assay for transposase-accessible chromatin-seqtherapeutic efficacytherapy efficacytranscriptometranscriptome sequencingtranscriptomic sequencingtranscriptomicstumortumor immune celltumor immune infiltratetumor immune microenvironmenttumor infiltration of immune cellstumor microenvironmenttumor-immune system interactionsα-ketoglutarateα-oxoglutarateαKG
Description preview
Molecular profiling of gliomas led to their genetic classification and a better understanding of their
pathophysiology. Adult mutant IDH1 gliomas are characterized by a mutation in the metabolic enzyme isocitrate
dehydrogenase 1 (IDH1) at active site residue R132. The mutation imparts a gain-of-function catalytic activity
which leads to the…
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