grant
Chromosomal instability as a driver of non-small cell lung cancer immune evasion and brain metastasis
Organization COLUMBIA UNIVERSITY HEALTH SCIENCESLocation NEW YORK, UNITED STATESPosted 1 Jul 2023Deadline 30 Jun 2028
NIHUS FederalResearch GrantFY2025AdenosineAntioncogene Protein p53BBB permeabilizationBBB permeableBehaviorBiologyBody TissuesBrainBrain MetastasisBrain Nervous SystemCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCancer BiologyCancer CauseCancer EtiologyCancer PatientCancersCas nuclease technologyCell BodyCell Communication and SignalingCell LineCell SignalingCellLineCellsCellular Tumor Antigen P53CephalicCessation of lifeCharacteristicsChromosomal InstabilityChromosome ArmChromosome InstabilityChromosome SegregationChronicClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCoupledCranialCytosolDNADNA mutationData BasesData SetDatabasesDeathDeoxyribonucleic AcidDevelopmentDiseaseDisorderDouble-Stranded DNADrug resistanceEncephalonEnvironmentEvolutionFailureFutureGENIEGenerationsGeneticGenetic ChangeGenetic EngineeringGenetic Engineering BiotechnologyGenetic Engineering Molecular BiologyGenetic defectGenetic mutationGoalsHumanImageImmune EvasionImmune mediated therapyImmunoglobulin Enhancer-Binding ProteinImmunologically Directed TherapyImmunomodulationImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapeutic agentImmunotherapyIn SituIn VitroInjectionsInterferon Type IIntracellular Communication and SignalingInvestigationKRAS(G12D)KRASG12DKinasesLKB1LKB1/STK11 GeneLabelLinkM PhaseMalignantMalignant - descriptorMalignant CellMalignant MelanomaMalignant NeoplasmsMalignant TumorMalignant Tumor of the LungMalignant neoplasm of lungMedical centerMelanomaMentorsMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic Neoplasm to the BrainMetastatic TumorMetastatic Tumor to the BrainMetastatic malignant neoplasm to brainMethodsMiceMice MammalsMitosisMitosis StageModelingModern ManMolecularMurineMusMutateMutationNF-kBNF-kappa BNF-kappaBNFKBNSCLCNSCLC - Non-Small Cell Lung CancerNeoplasm MetastasisNon-Small Cell Lung CancerNon-Small-Cell Lung CarcinomaNuclear Factor kappa BNuclear Transcription Factor NF-kBOncoprotein p53OutputP53Pathway interactionsPhosphoprotein P53Phosphoprotein pp53Phosphotransferase GenePhosphotransferasesPhysiciansPrimary NeoplasmPrimary TumorProcessProductionProtein TP53ProteinsPulmonary CancerPulmonary malignant NeoplasmRecombinant DNA TechnologyRecyclingResearchResistanceRiskRoleRuptureSTK11STK11 geneScientistSecondary NeoplasmSecondary TumorSignal TransductionSignal Transduction SystemsSignalingStimulator of Interferon GenesStrains Cell LinesSurfaceSystemTCGATP53TP53 geneTRP53TailTestingThe Cancer Genome AtlasTissuesTranscription Factor NF-kBTransphosphorylasesTumor CellTumor EscapeTumor Immune EscapeTumor PromotionTumor Protein p53Tumor Protein p53 GeneTumor SubtypeUniversitiesUpregulationValidationVeinsWorkbiological signal transductionblood-brain barrier permeabilizationblood-brain barrier permeablebloodbrain barrier permeabilizationbloodbrain barrier permeablebrain micrometastasiscGAMP STINGcGAMP-STINGcGAMP/STINGcGAS/STINGcancer cellcancer evasioncancer immune escapecancer immune evasioncancer metastasiscancer microenvironmentcancer progressioncancer typecareercheck point blockadecheckpoint blockadechromosome divisionchromosome losscombinatorialcultured cell linecyclic GMP-AMP synthase/STINGdata basedevelopmentaldrug resistantds-DNAdsDNAecto-nucleotidaseexperimentexperimental researchexperimental studyexperimentsgenetically engineeredgenome mutationgenome sequencinggenomic datagenomic datasetimagingimmune check point blockadeimmune checkpoint blockadeimmune drugsimmune evasiveimmune microenvironmentimmune modulationimmune regulationimmune suppressionimmune suppressive activityimmune suppressive functionimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapeuticsimmune-based therapiesimmune-based treatmentsimmuno therapyimmunologic reactivity controlimmunologic therapeuticsimmunomodulatoryimmunoregulationimmunoregulatoryimmunosuppressive activityimmunosuppressive functionimmunosuppressive microenvironmentimmunosuppressive responseimmunosuppressive tumor microenvironmentimmunotherapeuticsimmunotherapy agentin vivokappa B Enhancer Binding Proteinliver kinase B1lung cancermalignancymicronucleusmouse modelmulti-modalitymultimodalitymurine modelmutantneoplasm progressionneoplasm/cancerneoplastic cellneoplastic progressionnuclear factor kappa betap53 Antigenp53 Genesp53 Tumor Suppressorpathwayprotein p53refractory cancerresistance to Drugresistantresistant cancerresistant to Drugresponsesocial rolespatial and temporalspatial temporalspatiotemporaltherapeutic agent developmenttherapeutic developmenttranscriptomicstumortumor behaviortumor cell metastasistumor evasiontumor immune evasiontumor immune microenvironmenttumor microenvironmenttumor progressiontumor-immune system interactionsvalidations
Description preview
PROJECT SUMMARY/ABSTRACT
Brain metastasis (BM) frequently arises from non-small cell lung cancer (NSCLC) and represents the most
common cause of cancer related death in the US, yet our understanding of BM biology is rudimentary. Our group
has recently identified excessive chromosomal instability (CIN) as a hallmark of BM19. In in vitro studies, in…
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