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 ResearchConceptsT cell cytotoxicityCell cytotoxicityT cell killingTumor suppressorCancer patientsImmune responseAvailable agentsSurvival analysisClinical patientsCancer treatmentCancer cellsCancer resistanceDirect targetingPotential new conceptCancer mutationsPatientsCell killingNormal samplesResistance pathwaysCellular responsesSuch resistanceCytotoxicityResistance genes
2021
Genomic analyses of new genes and their phenotypic effects reveal rapid evolution of essential functions in Drosophila development
Xia S, VanKuren NW, Chen C, Zhang L, Kemkemer C, Shao Y, Jia H, Lee U, Advani AS, Gschwend A, Vibranovski MD, Chen S, Zhang YE, Long M. Genomic analyses of new genes and their phenotypic effects reveal rapid evolution of essential functions in Drosophila development. PLOS Genetics 2021, 17: e1009654. PMID: 34242211, PMCID: PMC8270118, DOI: 10.1371/journal.pgen.1009654.Peer-Reviewed Original ResearchConceptsNew genesPhenotypic effectsEssential functionsLong evolutionary time scalesDevelopment of DrosophilaEvolutionary time scalesDrosophila developmentDrosophila genusEssential genesGene essentialityRNAi libraryYoung genesGenomic analysisCRISPR knockoutKnockout approachGenetic basisKnockdown experimentsComputational identificationGene effectsGenesDuplicate copiesRapid evolutionDrosophilaKnockdown efficiencyDistant ancestors
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 ResearchConceptsImmune 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
Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer
Craig M, Kaveh K, Woosley A, Brown AS, Goldman D, Eton E, Mehta RM, Dhawan A, Arai K, Rahman MM, Chen S, Nowak MA, Goldman A. Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer. PLOS Computational Biology 2019, 15: e1007278. PMID: 31449515, PMCID: PMC6709889, DOI: 10.1371/journal.pcbi.1007278.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCoculture TechniquesComputational BiologyComputer SimulationCRISPR-Cas SystemsDEAD-box RNA HelicasesDrug Resistance, MultipleDrug Resistance, NeoplasmHumansLung NeoplasmsModels, BiologicalMutationRibonuclease IIIConceptsCancer cellsCell state transitionsWild-type cellsCooperative adaptationNon-small cell lung cancer cellsInterspecies competitionCell lung cancer cellsCRISPR/Drug-sensitive cellsLung cancer cellsNSCLC patient samplesDruggable targetsDrug pressureMutantsFlow cytometry dataPhenotypic heterogeneitySensitive cells
2018
Programmable sequential mutagenesis by inducible Cpf1 crRNA array inversion
Chow RD, Kim HR, Chen S. Programmable sequential mutagenesis by inducible Cpf1 crRNA array inversion. Nature Communications 2018, 9: 1903. PMID: 29765043, PMCID: PMC5954137, DOI: 10.1038/s41467-018-04158-z.Peer-Reviewed Original ResearchMapping 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 ResearchConceptsTumor 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
2017
AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma
Chow RD, Guzman CD, Wang G, Schmidt F, Youngblood MW, Ye L, Errami Y, Dong MB, Martinez MA, Zhang S, Renauer P, Bilguvar K, Gunel M, Sharp PA, Zhang F, Platt RJ, Chen S. AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma. Nature Neuroscience 2017, 20: 1329-1341. PMID: 28805815, PMCID: PMC5614841, DOI: 10.1038/nn.4620.Peer-Reviewed Original Research
2014
CRISPR-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 PhosphohydrolaseGenome editing with Cas9 in adult mice corrects a disease mutation and phenotype
Yin H, Xue W, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp PA, Jacks T, Anderson DG. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nature Biotechnology 2014, 32: 551-553. PMID: 24681508, PMCID: PMC4157757, DOI: 10.1038/nbt.2884.Peer-Reviewed Original Research
2011
Highly Tissue Specific Expression of Sphinx Supports Its Male Courtship Related Role in Drosophila melanogaster
Chen Y, Dai H, Chen S, Zhang L, Long M. Highly Tissue Specific Expression of Sphinx Supports Its Male Courtship Related Role in Drosophila melanogaster. PLOS ONE 2011, 6: e18853. PMID: 21541324, PMCID: PMC3082539, DOI: 10.1371/journal.pone.0018853.Peer-Reviewed Original ResearchMeSH KeywordsAnimal StructuresAnimalsBase PairingBase SequenceBrainConserved SequenceCourtshipDrosophila melanogasterFemaleGene Expression ProfilingGene Expression RegulationGenome, InsectGreen Fluorescent ProteinsMaleMolecular Sequence DataMutationOrgan SpecificityPeripheral Nervous SystemPromoter Regions, GeneticRNA, UntranslatedSexual Behavior, AnimalTransformation, GeneticConceptsDrosophila melanogasterBp regionCourtship behaviorNon-coding RNA genesWhole genome expression profilingBp upstream regionTissue-specific expressionGenome expression profilingMale courtship behaviorMale accessory glandsMelanogaster subgroupDrosophila speciesD. virilisRNA genesGene categoriesProtein functionKnockout mutationsWing hairsMale courtshipTarget genesExpression profilingGFP signalNegative regulatorEnhancer elementsExpression signals
2008
The evolution of courtship behaviors through the origination of a new gene in Drosophila
Dai H, Chen Y, Chen S, Mao Q, Kennedy D, Landback P, Eyre-Walker A, Du W, Long M. The evolution of courtship behaviors through the origination of a new gene in Drosophila. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 7478-7483. PMID: 18508971, PMCID: PMC2396706, DOI: 10.1073/pnas.0800693105.Peer-Reviewed Original ResearchConceptsMale-male courtshipD. melanogasterChimeric geneCourtship behaviorNew genesRelated Drosophila speciesNew chimeric genesDrosophila speciesAdaptive evolutionMutant phenotypeDrosophila melanogasterAncestral conditionUnrelated genesPhenotypic effectsMelanogasterNovel phenotypesCombination of sequenceMating behaviorChimeric structureGenesCourtshipSpeciesPhenotypeDrosophilaKnockout
2003
RNA-dependent RNA polymerase gene sequence from foot-and-mouth disease virus in Hong Kong
Chen X, Feng Q, Wu Z, Liu Y, Huang K, Shi R, Chen S, Lu W, Ding M, Collins R, Fung Y, Lau L, Yu A, Chen J. RNA-dependent RNA polymerase gene sequence from foot-and-mouth disease virus in Hong Kong. Biochemical And Biophysical Research Communications 2003, 308: 899-905. PMID: 12927804, DOI: 10.1016/s0006-291x(03)01511-0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceBase SequenceCloning, MolecularConserved SequenceDNA-Directed RNA PolymerasesFoot-and-Mouth Disease VirusGenetic VariationHong KongModels, GeneticMolecular Sequence DataMutationPhylogenyProtein Structure, TertiaryReverse Transcriptase Polymerase Chain ReactionRNA, ViralRNA-Dependent RNA PolymeraseSequence Analysis, DNASequence Homology, Amino AcidConceptsRNA-dependent RNA polymerase gene sequencesNucleotide sequenceRNA polymerase gene sequencesViral RNA-dependent RNA polymeraseRNA-dependent RNA polymeraseAmino acid sequenceAmino acid residuesMouth disease virusPolymerase gene sequencesCommon ancestorEvolutionary treeRNA polymeraseGene sequencesSequence comparisonAcid sequenceSame geneN-terminusDisease virusAcid residuesGenesFunctional relevanceRepresentative isolatesHost immune systemFMDV isolatesHKN/2002