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 deficiencyIn vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy
Peng L, Renauer P, Sferruzza G, Yang L, Zou Y, Fang Z, Park J, Chow R, Zhang Y, Lin Q, Bai M, Sanchez A, Zhang Y, Lam S, Ye L, Chen S. In vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy. Nature Biotechnology 2024, 1-10. PMID: 38918616, DOI: 10.1038/s41587-024-02282-4.Peer-Reviewed Original ResearchPrimary NK cellsTumor-infiltrating NKCAR-NK cellsNK cellsGenetic checkpointsNatural killerChimeric antigen receptor (CAR)-NK cellsHuman primary NK cellsSolid tumor mouse modelNK cell-based immunotherapyIn vivo antitumor efficacyCAR-NK therapyNK cell therapyCell-based immunotherapyNK cell functionTumor mouse modelTumor infiltrationAntitumor efficacyCell therapyCytokine productionEnhanced cytotoxicityMouse modelSingle-cell transcriptomic landscapeClinical potentialCell functionApplications 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 StatementsConvergent 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 ResearchConceptsSingle-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 tumorsHostVariant-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
CTLA-4 tail fusion enhances CAR-T antitumor immunity
Zhou X, Cao H, Fang S, Chow R, Tang K, Majety M, Bai M, Dong M, Renauer P, Shang X, Suzuki K, Levchenko A, Chen S. CTLA-4 tail fusion enhances CAR-T antitumor immunity. Nature Immunology 2023, 24: 1499-1510. PMID: 37500885, PMCID: PMC11344484, DOI: 10.1038/s41590-023-01571-5.Peer-Reviewed Original ResearchConceptsCytoplasmic tailSingle-cell RNA sequencingRNA sequencingC-terminusTail fusionCell engineering techniquesAntigen receptorFurther characterizationCytometry analysisSurface expressionCAR functionLow surface expressionCellsUnique strategyT cellsPowerful therapeuticsFusionEndocytosisLeukemia modelTerminusTailSequencingPhenotypeReduced activationEngineering techniquesPolyvalent 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 ResearchMassively 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
Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2
Fang Z, Peng L, Lucas C, Lin Q, Zhou L, Yang L, Feng Y, Ren P, Renauer PA, Monteiro VS, Hahn AM, Park JJ, Zhou X, Grubaugh N, Wilen C, Chen S. Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2. Cell Discovery 2022, 8: 69. PMID: 35853867, PMCID: PMC9295082, DOI: 10.1038/s41421-022-00435-w.Peer-Reviewed Original ResearchMultiplexed 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 cellsOmicron-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-mRNABooster
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 cellsHypomethylation of STAT1 and HLA-DRB1 is associated with type-I interferon-dependent HLA-DRB1 expression in lupus CD8+ T cells.
Miller S, Tsou PS, Coit P, Gensterblum-Miller E, Renauer P, Rohraff DM, Kilian NC, Schonfeld M, Sawalha AH. Hypomethylation of STAT1 and HLA-DRB1 is associated with type-I interferon-dependent HLA-DRB1 expression in lupus CD8+ T cells. Ann Rheum Dis 2019, 78: 519-528. PMID: 30674474, DOI: 10.1136/annrheumdis-2018-214323.Peer-Reviewed Original Research
2018
CD4+CD28+KIR+CD11a(hi) T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients.
Gensterblum E, Renauer P, Coit P, Strickland FM, Kilian NC, Miller S, Ognenovski M, Wren JD, Tsou PS, Lewis EE, Maksimowicz-McKinnon K, McCune WJ, Richardson BC, Sawalha AH. CD4+CD28+KIR+CD11a(hi) T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients. J Autoimmun 2018, 86: 19-28. PMID: 29066026, DOI: 10.1016/j.jaut.2017.09.011.Peer-Reviewed Original Research
2017
Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target.
Knight JS, Meng H, Coit P, Yalavarthi S, Sule G, Gandhi AA, Grenn RC, Mazza LF, Ali RA, Renauer P, Wren JD, Bockenstedt PL, Wang H, Eitzman DT, Sawalha AH. Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target. JCI Insight 2017, 2 PMID: 28931754, DOI: 10.1172/jci.insight.93897.Peer-Reviewed Original ResearchAAV-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 ResearchThe genetics of Takayasu arteritis.
Renauer P, Sawalha AH. The genetics of Takayasu arteritis. Presse Med 2017, 46: e179-e187. PMID: 28756073, DOI: 10.1016/j.lpm.2016.11.031.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements