grant
MECHANISMS OF POL II ELONGATION IN DIFFUSE MIDLINE GLIOMA
Organization BAYLOR COLLEGE OF MEDICINELocation HOUSTON, UNITED STATESPosted 15 Feb 2023Deadline 31 Jan 2028
NIHUS FederalResearch GrantFY20250-11 years old21+ years oldAblationAdultAdult HumanAnti-Cancer AgentsAntineoplastic AgentsAntineoplastic DrugsAntineoplasticsAutomobile DrivingBindingBinding SitesBrain CancerBrain NeoplasiaBrain NeoplasmsBrain TumorsCRISPRCRISPR editing screenCRISPR screenCRISPR-based screenCRISPR/Cas systemCRISPR/Cas9 screenCancer DrugCancer GenesCancer TreatmentCancer-Promoting GeneCancersCell BodyCellsChemicalsChildChild YouthChildhoodChildren (0-21)ChromatinChromatin StructureClinical TrialsClustered Regularly Interspaced Short Palindromic RepeatsCombining SiteComplexDIPGDNA Polymerase IIDNA Polymerase epsilonDNA mutationDNA-Dependent DNA Polymerase IIDNA-Dependent RNA Polymerase IIDataDefectDependenceDevelopmentDiagnosisDiffuseDiffuse intrinsic pontine gliomaDiseaseDisorderDrugsElongation FactorExhibitsExpression SignatureGene AbnormalityGene Action RegulationGene ExpressionGene Expression ProfileGene Expression RegulationGene RegulationGene Regulation ProcessGene TargetingGene TranscriptionGeneralized GrowthGenesGeneticGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGenomicsGlial Cell TumorsGlial NeoplasmGlial TumorGliomaGliomagenesisGoalsGrowthH3 K27M mutantH3 K27M mutationH3K27M mutantH3K27M mutationHeterograftHeterologous TransplantationHistone H3HistonesInvestigationKnock-outKnockoutKnowledgeLinkMalignantMalignant - descriptorMalignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMalignant Tumor of the BrainMalignant neoplasm of brainMeasuresMedicationMiceMice MammalsMolecularMolecular InteractionMurineMusMutationNGS MethodNGS systemNeoplastic Disease Chemotherapeutic AgentsNeuroglial NeoplasmNeuroglial TumorNormal CellNormal TissueNormal tissue morphologyOncogenesOncogenesisOncogenicOutputPathway interactionsPatientsPatternPharmaceutical PreparationsPol IIPolymerasePonsPons CerebelliPons VaroliiPontinePontine structureProliferatingProteinsRNA ExpressionRNA Polymerase BRNA Polymerase IIRNA SeqRNA sequencingRNAseqReactive SiteRegulationRegulatory PathwayRegulatory ProteinResearchRoleSIII elongation factorSomatic MutationTF-SIIITissue GrowthTranscriptionTranscription ElongationTransforming GenesTumor Suppressor ProteinsTumor-Specific Treatment AgentsVHL Tumor Suppressor ProteinVHL gene productVHL proteinVon Hippel-Lindau Tumor Suppressor ProteinWorkXenograftXenograft ModelXenograft procedureXenotransplantationadulthoodanti-cancer druganti-cancer therapybrain tissuecancer cellcancer progressioncancer therapycancer-directed therapycell typechromatin modificationclustered regularly interspaced short palindromic repeats screendevelopmentaldiffuse midline gliomadrivingdrug/agenteffective therapyeffective treatmentelonginelongin Bepigenomegene expression patterngene expression signaturegenetic regulatory proteingenome mutationgenome scalegenome-widegenomewideglial-derived tumorglioma genesisimprovedinhibitorinsightkidsmalignancymouse modelmurine modelmutantneoplasm progressionneoplasm/cancerneoplastic progressionneuroglia neoplasmneuroglia tumornext gen sequencingnext generation sequencingnextgen sequencingnon-synonymous mutationnonsynonymous mutationnonsynonymous single nucleotide polymorphismnonsynonymous single nucleotide variantnonsynonymous single-nucleotide substitutionnonsynonymous variantnovelontogenyoverexpressoverexpressionpathwaypediatricpre-clinicalpreclinicalprogramsregulatory gene productsocial rolesomatic varianttargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttissue culturetranscription factor SIIItranscriptional profiletranscriptional signaturetranscriptome sequencingtranscriptomic sequencingtranscriptomicstreatment strategytumortumor growthtumor initiationtumor progressiontumor suppressortumorigenesistumors in the brainvon Hippel Lindau disease gene productvon Hippel Lindau disease proteinvon Hippel Lindau gene productvon Hippel Lindau proteinxeno-transplantxeno-transplantationxenograft transplant modelxenotransplant modelyoungster
Description preview
Project Summary/Abstract
Diffuse midline gliomas (DMGs) are aggressive brain tumors in both children and adults with no effective
therapies. Over 80% of pediatric DMG and a majority of adult DMG harbor non-synonymous mutations in histone
H3 (H3.3K27M and H3.1K27M), which dysregulate chromatin and result in aberrant Pol II transcription in brain…
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