Featured Publications
Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.
Renauer P, Park J, Bai M, Acosta A, Lee W, Lin G, Zhang Y, Dai X, Wang G, Errami Y, Wu T, Clark P, Ye L, Yang Q, Chen S. Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function. Cancer Immunology Research 2023, 11: 1068-1084. PMID: 37253111, PMCID: PMC10527769, DOI: 10.1158/2326-6066.cir-22-0565.Peer-Reviewed Original ResearchConceptsCAR T cellsHER2-specific CAR T cellsT cellsTumor microenvironmentChimeric antigen receptor T cellsT cell-based immunotherapyAntigen receptor T cellsCD19-specific chimeric antigen receptor (CAR) T cellsCAR T-cell therapyCell-based immunotherapyReceptor T cellsT-cell therapyVivo colorectal cancer modelsColorectal cancer modelT cell functionT cell metabolismTumor infiltrationEvasion mechanismsImmunosuppressive metaboliteImmune evasionCancer modelImmunologic analysisCD19-specificUnfavorable tumor microenvironmentPDK1 deficiencyApplications of CRISPR technology in cellular immunotherapy
Zhou X, Renauer P, Zhou L, Fang S, Chen S. Applications of CRISPR technology in cellular immunotherapy. Immunological Reviews 2023, 320: 199-216. PMID: 37449673, PMCID: PMC10787818, DOI: 10.1111/imr.13241.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsVariant-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-19Vaccination
2023
Massively parallel knock-in engineering of human T cells
Dai X, Park J, Du Y, Na Z, Lam S, Chow R, Renauer P, Gu J, Xin S, Chu Z, Liao C, Clark P, Zhao H, Slavoff S, Chen S. Massively parallel knock-in engineering of human T cells. Nature Biotechnology 2023, 41: 1239-1255. PMID: 36702900, PMCID: PMC11260498, DOI: 10.1038/s41587-022-01639-x.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
Multiplexed 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 cells
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
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 cells
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