2023
Polyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens
Fang Z, Monteiro V, Renauer P, Shang X, Suzuki K, Ling X, Bai M, Xiang Y, Levchenko A, Booth C, Lucas C, Chen S. Polyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens. Cell Research 2023, 33: 407-410. PMID: 36879038, PMCID: PMC9988199, DOI: 10.1038/s41422-023-00792-5.Peer-Reviewed Original ResearchRAMIHM generates fully human monoclonal antibodies by rapid mRNA immunization of humanized mice and BCR-seq
Ren P, Peng L, Yang L, Suzuki K, Fang Z, Renauer P, Lin Q, Bai M, Li T, Clark P, Klein D, Chen S. RAMIHM generates fully human monoclonal antibodies by rapid mRNA immunization of humanized mice and BCR-seq. Cell Chemical Biology 2023, 30: 85-96.e6. PMID: 36640761, PMCID: PMC9868106, DOI: 10.1016/j.chembiol.2022.12.005.Peer-Reviewed Original ResearchConceptsHuman monoclonal antibodyHumanized miceMonoclonal antibodiesMemory B cell populationsHumanized transgenic miceBroad antibody responseB cell populationsG protein-coupled receptor targetsNeutralizing antibodiesPeripheral bloodAntibody responseImmunotherapy targetClinical vaccinesPlasma BCell sequencingTransgenic miceImmunization methodReceptor targetsAntibodiesMiceCell populationsHigh potencyImmunizationHigh rateAntibody discovery
2022
Mapping subcellular localizations of unannotated microproteins and alternative proteins with MicroID
Na Z, Dai X, Zheng SJ, Bryant CJ, Loh KH, Su H, Luo Y, Buhagiar AF, Cao X, Baserga SJ, Chen S, Slavoff SA. Mapping subcellular localizations of unannotated microproteins and alternative proteins with MicroID. Molecular Cell 2022, 82: 2900-2911.e7. PMID: 35905735, PMCID: PMC9662605, DOI: 10.1016/j.molcel.2022.06.035.Peer-Reviewed Original ResearchConceptsSubcellular localizationProximity biotinylationSmall open reading framesAlternative proteinsOpen reading frameHigh-throughput technologiesSubnuclear organellesCanonical proteinsRRNA transcriptionSubcellular compartmentsReading frameProteogenomic identificationProtein compositionAmino acidsMicroproteinsProteinBiotinylationLocalizationTurboIDTranscriptionOrganellesMouse modelPolypeptideNucleoliExpressionMultiplexed LNP-mRNA vaccination against pathogenic coronavirus species
Peng L, Fang Z, Renauer PA, McNamara A, Park JJ, Lin Q, Zhou X, Dong MB, Zhu B, Zhao H, Wilen CB, Chen S. Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species. Cell Reports 2022, 40: 111160. PMID: 35921835, PMCID: PMC9294034, DOI: 10.1016/j.celrep.2022.111160.Peer-Reviewed Original ResearchConceptsAntibody responseCoronavirus speciesSequential vaccinationSARS-CoVAntigen-specific antibody responsesSARS-CoV-2 DeltaAdaptive immune cellsEffective immune responsePotent antibody responsesCOVID-19 vaccineSARS-CoV-2MRNA vaccine candidatesActivated B cellsSingle-cell RNA sequencing profilesRNA sequencing profilesSimultaneous vaccinationAntibody immunityVaccination scheduleImmune profileImmune cellsImmune responseVaccine candidatesMERS-CoV.Animal modelsB cellsDevelopment of an efficient reproducible cell-cell transmission assay for rapid quantification of SARS-CoV-2 spike interaction with hACE2
Ssenyange G, Kerfoot M, Zhao M, Farhadian S, Chen S, Peng L, Ren P, Dela Cruz CS, Gupta S, Sutton RE. Development of an efficient reproducible cell-cell transmission assay for rapid quantification of SARS-CoV-2 spike interaction with hACE2. Cell Reports Methods 2022, 2: 100252. PMID: 35757815, PMCID: PMC9213030, DOI: 10.1016/j.crmeth.2022.100252.Peer-Reviewed Original ResearchConceptsAnti-spike monoclonal antibodiesTransmission assaysTherapeutic antiviral drugsSARS-CoV-2Quantitative readoutVirus-cell bindingRapid quantificationConvalescent seraNeutralization assaysAntiviral drugsResearch reagentsSmall molecule drugsClinical settingViral replicationPseudotyped particlesMonoclonal antibodiesLaboratory equipmentQuantitative assayOmicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2
Fang Z, Peng L, Filler R, Suzuki K, McNamara A, Lin Q, Renauer PA, Yang L, Menasche B, Sanchez A, Ren P, Xiong Q, Strine M, Clark P, Lin C, Ko AI, Grubaugh ND, Wilen CB, Chen S. Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2. Nature Communications 2022, 13: 3250. PMID: 35668119, PMCID: PMC9169595, DOI: 10.1038/s41467-022-30878-4.Peer-Reviewed Original ResearchConceptsHeterologous boosterSARS-CoV-2Antibody responseMRNA vaccinesMRNA vaccinationDelta variantOmicron variantType of vaccinationStrong antibody responseMRNA vaccine candidatesVaccine candidatesNeutralization potencyImmune evasionSARS-CoV.Two weeksComparable titersVaccinationVaccineTiters 10MiceOmicronWeeksWA-1LNP-mRNABoosterVariant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2
Peng L, Renauer PA, Ökten A, Fang Z, Park JJ, Zhou X, Lin Q, Dong MB, Filler R, Xiong Q, Clark P, Lin C, Wilen CB, Chen S. Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2. Cell Reports Medicine 2022, 3: 100634. PMID: 35561673, PMCID: PMC9040489, DOI: 10.1016/j.xcrm.2022.100634.Peer-Reviewed Original ResearchConceptsImmune responseImmune cell populationsSARS-CoV-2 spikeAssessment of efficacySARS-CoV-2LNP-mRNABreakthrough infectionsCD8 TImmune profilingMRNA vaccinesPotent protectionT lymphocytesNeutralization activityDelta variantAnimal modelsPotent antibodiesRepertoire diversityCell responsesAuthentic virusSystemic increaseVariant lineagesClonal expansionCell populationsCOVID-19VaccinationMonospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617
Peng L, Hu Y, Mankowski MC, Ren P, Chen RE, Wei J, Zhao M, Li T, Tripler T, Ye L, Chow RD, Fang Z, Wu C, Dong MB, Cook M, Wang G, Clark P, Nelson B, Klein D, Sutton R, Diamond MS, Wilen CB, Xiong Y, Chen S. Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617. Nature Communications 2022, 13: 1638. PMID: 35347138, PMCID: PMC8960874, DOI: 10.1038/s41467-022-29288-3.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Authentic SARS-CoV-2Effective therapeutic optionPotent SARS-CoV-2SARS-CoV-2 variantsVariants of concernRepertoire of therapeuticsBreakthrough infectionsTherapeutic optionsMultiple vaccinesPathogen SARS-CoV-2Delta variantB cellsPotent efficacyHumanized antibodyDistinct epitopesBispecific antibodiesOriginal virusSpike receptorStrong inhibitory activityMonoclonal antibodiesAntibodiesStrong potencyLead clonesLead antibodiesHigh-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19Patients
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 landscapeBlockadeCancerNonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA
Yuan S, Peng L, Park JJ, Hu Y, Devarkar SC, Dong MB, Shen Q, Wu S, Chen S, Lomakin IB, Xiong Y. Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA. Molecular Cell 2020, 80: 1055-1066.e6. PMID: 33188728, PMCID: PMC7833686, DOI: 10.1016/j.molcel.2020.10.034.Peer-Reviewed Original ResearchConceptsInternal ribosome entry site RNANonstructural protein 1Host protein synthesis machineryMRNA entry channelProtein synthesis machineryCryo-EM structureProtein 1Major pathogenicity factorsDifferential expression analysisMRNA-seq dataCellular transcriptomePreinitiation complexSynthesis machineryHuman lung originTranslation inhibitionPathogenicity factorsExpression analysisSite RNAHost viabilityNSP1Protein synthesisEntry channelViral proteinsUnknown mechanismViral RNA
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 treatmentIn vivo CRISPR screening in CD8 T cells with AAV–Sleeping Beauty hybrid vectors identifies membrane targets for improving immunotherapy for glioblastoma
Ye L, Park JJ, Dong MB, Yang Q, Chow RD, Peng L, Du Y, Guo J, Dai X, Wang G, Errami Y, Chen S. In vivo CRISPR screening in CD8 T cells with AAV–Sleeping Beauty hybrid vectors identifies membrane targets for improving immunotherapy for glioblastoma. Nature Biotechnology 2019, 37: 1302-1313. PMID: 31548728, PMCID: PMC6834896, DOI: 10.1038/s41587-019-0246-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCD8-Positive T-LymphocytesCell Line, TumorCRISPR-Cas SystemsDependovirusFemaleGene EditingGlioblastomaHumansImmunotherapy, AdoptiveLymphocyte Activation Gene 3 ProteinMaleMembrane ProteinsMiceN-AcetylglucosaminyltransferasesNeoplasm ProteinsProtein Disulfide-IsomerasesReceptors, Cell SurfaceRNA, Guide, CRISPR-Cas SystemsTransposasesXenograft Model Antitumor AssaysConceptsRNA cassetteMembrane protein targetsPrimary murine T cellsGenetic screening systemSingle-cell sequencingScreen hitsSleeping Beauty (SB) transposonCRISPR screensMembrane proteinsCell sequencingT cellsAdeno-associated virusGenomic integrationMembrane targetsMurine T cellsProtein targetsEfficient geneHuman GBM cellsGene editingT cell receptor transgenic modelGBM cellsBeauty transposonPDIA3T cell-based immunotherapyAntigen-specific killingSystematic 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 Research
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 ResearchCancer 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.BooksMapping 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
Diverse Class 2 CRISPR-Cas Effector Proteins for Genome Engineering Applications
Pyzocha NK, Chen S. Diverse Class 2 CRISPR-Cas Effector Proteins for Genome Engineering Applications. ACS Chemical Biology 2017, 13: 347-356. PMID: 29121460, PMCID: PMC6768076, DOI: 10.1021/acschembio.7b00800.Peer-Reviewed Original ResearchConceptsGenome engineering applicationsCRISPR-Cas genome editing technologiesMicrobial adaptive immune systemGenome editing technologyEffector enzymeNucleic acid cleavageEditing technologyUnique propertiesModern molecular biologyEngineering applicationsEffector proteinsMammalian cellsMolecular biologyAdaptive immune systemWide diversityTechnologyEnzymeApplicationsFunctionalityAcid cleavageImmune systemBiologyProteinDNADiversity