2022
Double knockout CRISPR screen for cancer resistance to T cell cytotoxicity
Park J, Codina A, Ye L, Lam S, Guo J, Clark P, Zhou X, Peng L, Chen S. Double knockout CRISPR screen for cancer resistance to T cell cytotoxicity. Journal Of Hematology & Oncology 2022, 15: 172. PMID: 36456981, PMCID: PMC9716677, DOI: 10.1186/s13045-022-01389-y.Peer-Reviewed Original ResearchMeSH KeywordsClustered Regularly Interspaced Short Palindromic RepeatsHumansImmunotherapyMutationNeoplasmsT-LymphocytesConceptsT cell cytotoxicityCell cytotoxicityT cell killingTumor suppressorCancer patientsImmune responseAvailable agentsSurvival analysisClinical patientsCancer treatmentCancer cellsCancer resistanceDirect targetingPotential new conceptCancer mutationsPatientsCell killingNormal samplesResistance pathwaysCellular responsesSuch resistanceCytotoxicityResistance genesA genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy
Ye L, Park JJ, Peng L, Yang Q, Chow RD, Dong MB, Lam SZ, Guo J, Tang E, Zhang Y, Wang G, Dai X, Du Y, Kim HR, Cao H, Errami Y, Clark P, Bersenev A, Montgomery RR, Chen S. A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy. Cell Metabolism 2022, 34: 595-614.e14. PMID: 35276062, PMCID: PMC8986623, DOI: 10.1016/j.cmet.2022.02.009.Peer-Reviewed Original ResearchMeSH KeywordsCD8-Positive T-LymphocytesClustered Regularly Interspaced Short Palindromic RepeatsGain of Function MutationHumansNeoplasmsProlineReceptors, Chimeric AntigenConceptsCAR T cellsT cell-based immunotherapyRight molecular targetCell-based immunotherapyCAR-T therapyChimeric antigen receptorMultiple cancer modelsCAR-T efficacyFunction CRISPR screensCD8 TPrimary CD8Immune functionImmunological diseasesImmune boosterCancer modelAntigen receptorDistinct gene expressionMolecular targetsCRISPR activation screensMetabolic programsImmunological analysisTherapyCancerEfficacyActivation screens
2021
Tumor immunology CRISPR screening: present, past, and future
Dong MB, Tang K, Zhou X, Zhou JJ, Chen S. Tumor immunology CRISPR screening: present, past, and future. Trends In Cancer 2021, 8: 210-225. PMID: 34920978, PMCID: PMC8854335, DOI: 10.1016/j.trecan.2021.11.009.Peer-Reviewed Original ResearchMeSH KeywordsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGene EditingHumansImmunotherapyNeoplasms
2020
CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade
Wang G, Chow RD, Zhu L, Bai Z, Ye L, Zhang F, Renauer PA, Dong MB, Dai X, Zhang X, Du Y, Cheng Y, Niu L, Chu Z, Kim K, Liao C, Clark P, Errami Y, Chen S. CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade. Cancer Discovery 2020, 10: 1912-1933. PMID: 32887696, PMCID: PMC7710536, DOI: 10.1158/2159-8290.cd-19-1448.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClustered Regularly Interspaced Short Palindromic RepeatsDNA-Binding ProteinsHumansImmune Checkpoint InhibitorsMiceMutationNeoplasm ProteinsConceptsImmune checkpoint blockadeCheckpoint blockadeCancer typesMajority of patientsRemarkable clinical efficacyFraction of patientsMajor modulatorComplex molecular landscapeMultiple cancer typesClinical efficacyICB responseImmune infiltrationTumor immunogenicityAntigen presentationMutation burdenMouse modelPatient stratificationMutant tumorsTumor microenvironmentIssue featurePatientsTumorsMolecular landscapeBlockadeCancer
2019
Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity
Wang G, Chow RD, Bai Z, Zhu L, Errami Y, Dai X, Dong MB, Ye L, Zhang X, Renauer PA, Park JJ, Shen L, Ye H, Fuchs CS, Chen S. Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity. Nature Immunology 2019, 20: 1494-1505. PMID: 31611701, PMCID: PMC6858551, DOI: 10.1038/s41590-019-0500-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigens, NeoplasmCancer VaccinesCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCoculture TechniquesCombined Modality TherapyDependovirusDisease Models, AnimalFemaleGene Expression Regulation, NeoplasticGenetic TherapyGenetic VectorsHEK293 CellsHumansImmunotherapyInjections, IntralesionalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsT-Lymphocytes, CytotoxicTumor MicroenvironmentConceptsAntitumor immunityImmune responseCell-based vaccination strategiesElicits potent antitumor immunityEnhanced T cell infiltrationElicit potent immune responsesCurrent immunotherapy modalitiesStrong antitumor immunityAntitumor immune responseT cell infiltrationPotent antitumor immunityPotent immune responsesAntitumor immune signaturesMultiple cancer typesImmune signaturesImmunotherapy modalitiesTreatment modalitiesCell infiltrationVaccination strategiesTumor antigensVirus deliveryTumor microenvironmentImmunotherapyCancer typesCancer treatmentSystematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells
Dong MB, Wang G, Chow RD, Ye L, Zhu L, Dai X, Park JJ, Kim HR, Errami Y, Guzman CD, Zhou X, Chen KY, Renauer PA, Du Y, Shen J, Lam SZ, Zhou JJ, Lannin DR, Herbst RS, Chen S. Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells. Cell 2019, 178: 1189-1204.e23. PMID: 31442407, PMCID: PMC6719679, DOI: 10.1016/j.cell.2019.07.044.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCD8-Positive T-LymphocytesCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCytokinesFemaleHumansImmunologic MemoryImmunotherapyMaleMiceMice, KnockoutNF-kappa BProgrammed Cell Death 1 ReceptorRNA HelicasesRNA, Guide, CRISPR-Cas SystemsTranscriptomeConceptsCRISPR screensTarget discoveryGenome-scale CRISPR screensCD8 TRNA helicase DHX37Vivo CRISPR screensGenetic screenGenome scaleTranscriptomic profilingBiochemical interrogationAntigen-specific CD8 TAnti-tumor immune responseFunctional regulatorTriple-negative breast cancerDHX37Essential roleTim-3PD-1Cytokine productionTumor infiltrationImmunotherapy targetImmunotherapy settingsRegulatorBreast cancerT cellsIn vivo profiling of metastatic double knockouts through CRISPR–Cpf1 screens
Chow RD, Wang G, Ye L, Codina A, Kim HR, Shen L, Dong MB, Errami Y, Chen S. In vivo profiling of metastatic double knockouts through CRISPR–Cpf1 screens. Nature Methods 2019, 16: 405-408. PMID: 30962622, PMCID: PMC6592845, DOI: 10.1038/s41592-019-0371-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9CRISPR-Cas SystemsEndonucleasesGene EditingGene Knockout TechniquesMiceNeoplasm MetastasisSequence Analysis, RNAOne-step generation of modular CAR-T cells with AAV–Cpf1
Dai X, Park JJ, Du Y, Kim HR, Wang G, Errami Y, Chen S. One-step generation of modular CAR-T cells with AAV–Cpf1. Nature Methods 2019, 16: 247-254. PMID: 30804551, PMCID: PMC6519746, DOI: 10.1038/s41592-019-0329-7.Peer-Reviewed Original ResearchCells, CulturedClustered Regularly Interspaced Short Palindromic RepeatsDependovirusGene EditingGene Knock-In TechniquesGene Knockdown TechniquesHumansReceptors, AntigenRepetitive Sequences, Nucleic AcidT-LymphocytesConvergent Identification and Interrogation of Tumor-Intrinsic Factors that Modulate Cancer Immunity In Vivo
Codina A, Renauer PA, Wang G, Chow RD, Park JJ, Ye H, Zhang K, Dong MB, Gassaway B, Ye L, Errami Y, Shen L, Chang A, Jain D, Herbst RS, Bosenberg M, Rinehart J, Fan R, Chen S. Convergent Identification and Interrogation of Tumor-Intrinsic Factors that Modulate Cancer Immunity In Vivo. Cell Systems 2019, 8: 136-151.e7. PMID: 30797773, PMCID: PMC6592847, DOI: 10.1016/j.cels.2019.01.004.Peer-Reviewed Original ResearchMeSH KeywordsClustered Regularly Interspaced Short Palindromic RepeatsGene Expression ProfilingNeoplasmsConceptsSingle-cell transcriptomic profilingExtracellular protein productionCancer cellsMutant cellsFunctional interrogationGenetic programCRISPR screensTranscriptomic profilingTumor-intrinsic mutationsTranscriptomic alterationsTumor microenvironmentProtein productionPRKAR1A lossGenetic makeupHost myeloid cellsTumor-intrinsic factorsDrastic alterationsCytometry analysisConvergent identificationMyeloid cellsCellsImmunocompetent hostsCancer immunityMutant tumorsHost
2018
Cancer CRISPR Screens In Vivo
Chow RD, Chen S. Cancer CRISPR Screens In Vivo. Trends In Cancer 2018, 4: 349-358. PMID: 29709259, PMCID: PMC5935117, DOI: 10.1016/j.trecan.2018.03.002.BooksAnimalsClustered Regularly Interspaced Short Palindromic RepeatsGene EditingGenomicsHumansMutagenesisNeoplasmsPrecision MedicineMapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR–mediated direct in vivo screening
Wang G, Chow RD, Ye L, Guzman CD, Dai X, Dong MB, Zhang F, Sharp PA, Platt RJ, Chen S. Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR–mediated direct in vivo screening. Science Advances 2018, 4: eaao5508. PMID: 29503867, PMCID: PMC5829971, DOI: 10.1126/sciadv.aao5508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisClustered Regularly Interspaced Short Palindromic RepeatsDependovirusGenes, Tumor SuppressorGenetic TestingGenomeLiverMiceMutationNeoplasmsConceptsTumor suppressorCancer Genome AtlasHuman cancersSgRNA target sitesGenome AtlasCancer Genomics ConsortiumPutative tumor suppressor geneNumerous human cancersTumor suppressor geneCRISPR screensClassical oncogenesGenomics ConsortiumSuppressor geneFunctional variantsFunctional consequencesMutational landscapeAutochthonous mouse modelSuppressorTarget siteAAV-CRISPRGenesMouse liverMultiple variantsLiver tumorigenesisVivo
2014
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
Platt RJ, Chen S, Zhou Y, Yim MJ, Swiech L, Kempton HR, Dahlman JE, Parnas O, Eisenhaure TM, Jovanovic M, Graham DB, Jhunjhunwala S, Heidenreich M, Xavier RJ, Langer R, Anderson DG, Hacohen N, Regev A, Feng G, Sharp PA, Zhang F. CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling. Cell 2014, 159: 440-455. PMID: 25263330, PMCID: PMC4265475, DOI: 10.1016/j.cell.2014.09.014.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsClustered Regularly Interspaced Short Palindromic RepeatsDendritic CellsDisease Models, AnimalGene Knock-In TechniquesGenes, Tumor SuppressorGenetic EngineeringGenetic VectorsLentivirusLung NeoplasmsMiceMice, TransgenicOncogenesCRISPR-mediated direct mutation of cancer genes in the mouse liver
Xue W, Chen S, Yin H, Tammela T, Papagiannakopoulos T, Joshi NS, Cai W, Yang G, Bronson R, Crowley DG, Zhang F, Anderson DG, Sharp PA, Jacks T. CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature 2014, 514: 380-384. PMID: 25119044, PMCID: PMC4199937, DOI: 10.1038/nature13589.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBeta CateninCell Transformation, NeoplasticClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsFemaleGenes, p53Genes, Tumor SuppressorGenetic EngineeringHepatocytesLipid MetabolismLiverLiver NeoplasmsMiceMolecular Sequence DataMutagenesisMutationOncogenesPhosphorylationProto-Oncogene Proteins c-aktPTEN Phosphohydrolase