Featured Publications
5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING
Tian J, Zhang D, Kurbatov V, Wang Q, Wang Y, Fang D, Wu L, Bosenberg M, Muzumdar MD, Khan S, Lu Q, Yan Q, Lu J. 5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING. The EMBO Journal 2021, 40: embj2020106065. PMID: 33615517, PMCID: PMC8013832, DOI: 10.15252/embj.2020106065.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityTumor burdenSubsequent type I interferon productionHigh STING expressionIntratumoral T cellsT-cell depletionType I interferon productionI interferon productionLoss of STINGImmunocompetent hostsColorectal specimensT cellsSTING expressionBetter survivalHigh doseTherapeutic effectivenessHuman colorectal specimensMelanoma tumorsInterferon productionChemotherapeutic drugsMurine colonImmunityEfficacyStingsColonThe DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression
Pan W, Zhu S, Qu K, Meeth K, Cheng J, He K, Ma H, Liao Y, Wen X, Roden C, Tobiasova Z, Wei Z, Zhao J, Liu J, Zheng J, Guo B, Khan SA, Bosenberg M, Flavell RA, Lu J. The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression. Immunity 2017, 47: 284-297.e5. PMID: 28813659, PMCID: PMC5710009, DOI: 10.1016/j.immuni.2017.07.020.Peer-Reviewed Original ResearchConceptsImmunosuppressive functionMyeloid cellsIntratumoral myeloid cellsNon-hematologic malignanciesMyeloid-specific deletionTumor-associated macrophagesReduced tumor growthTumor-promoting functionsProinflammatory onesMyD88 pathwayMelanoma patientsCell depletionEffector TRole of TET2Methylcytosine dioxygenase TET2Mouse modelIL-1RMelanoma growthTherapeutic targetTumor growthTET2 expressionMelanoma progressionHematopoietic malignanciesMalignancyTET2
2022
Bile acid distributions, sex-specificity, and prognosis in colorectal cancer
Cai Y, Shen X, Lu L, Yan H, Huang H, Gaule P, Muca E, Theriot CM, Rattray Z, Rattray NJW, Lu J, Ahuja N, Zhang Y, Paty PB, Khan SA, Johnson CH. Bile acid distributions, sex-specificity, and prognosis in colorectal cancer. Biology Of Sex Differences 2022, 13: 61. PMID: 36274154, PMCID: PMC9590160, DOI: 10.1186/s13293-022-00473-9.Peer-Reviewed Original ResearchConceptsLeft-sided colon tumorsRight-sided colon tumorsColon cancer patientsColorectal cancerTumor locationBile acidsColon tumorsCancer patientsQuantitative immunofluorescencePrimary tumor locationImmune regulatory cellsRecurrence-free survivalBile acid metabolismSecondary bile acidsBile acid distributionBile acid analysisBackgroundBile acidsOverall survivalRegulatory cellsCRC patientsMale patientsPatient sexImmune cellsPatient prognosisImmune response
2021
Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes
Rui J, Deng S, Perdigoto AL, Ponath G, Kursawe R, Lawlor N, Sumida T, Levine-Ritterman M, Stitzel ML, Pitt D, Lu J, Herold KC. Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes. Nature Communications 2021, 12: 5074. PMID: 34417463, PMCID: PMC8379260, DOI: 10.1038/s41467-021-25367-z.Peer-Reviewed Original ResearchConceptsImmune cellsΒ-cellsNOD/SCID recipientsDiabetogenic immune cellsDiabetogenic T cellsBone marrow transplantType 1 diabetesExpression of TET2Human β-cellsIslet infiltratesSCID recipientsMarrow transplantInflammatory pathwaysTransfer of diseaseT cellsInflammatory genesImmune killingPathologic interactionsReduced expressionDiabetesInflammationTET2MiceRecipientsCells
2019
Digital Inference of Immune Microenvironment Reveals Low-Risk Subtype of Early Lung Adenocarcinoma
Kurbatov V, Balayev A, Saffarzadeh A, Heller DR, Boffa DJ, Blasberg JD, Lu J, Khan SA. Digital Inference of Immune Microenvironment Reveals Low-Risk Subtype of Early Lung Adenocarcinoma. The Annals Of Thoracic Surgery 2019, 109: 343-349. PMID: 31568747, DOI: 10.1016/j.athoracsur.2019.08.050.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAdultAgedCohort StudiesDatabases, FactualDisease-Free SurvivalFemaleHumansImmunotherapyKaplan-Meier EstimateLung NeoplasmsMaleMiddle AgedNeoplasm InvasivenessNeoplasm StagingPneumonectomyPrognosisProportional Hazards ModelsRetrospective StudiesRisk AssessmentSurvival AnalysisTumor MicroenvironmentConceptsTumor immune microenvironmentImmune microenvironmentLung adenocarcinomaOverall survivalRisk groupsMast cellsCox proportional hazard modelingEarly-stage lung adenocarcinomaLow-risk subtypesKaplan-Meier analysisPathological staging systemProportional hazard modelingImproved clinical outcomesCancer immune microenvironmentImmune cell typesEarly lung adenocarcinomaActivation stateClinical outcomesValidation cohortMacrophage contentStaging systemMultivariable modelCIBERSORT analysisPatientsClinical decisionMKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation
Hu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.Peer-Reviewed Original ResearchConceptsCell fate reprogrammingChromatin accessibilityActin cytoskeletonSomatic cell reprogrammingPluripotency transcription factorsGlobal chromatin accessibilityGenomic accessibilityCytoskeleton (LINC) complexCell reprogrammingCytoskeletal genesTranscription factorsReprogrammingPluripotencyChromatinCytoskeletonMKL1Unappreciated aspectPathwayNuclear volumeNucleoskeletonSUN2CellsActivationGenesExpression
2017
Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells
Zhu S, Ding S, Wang P, Wei Z, Pan W, Palm NW, Yang Y, Yu H, Li HB, Wang G, Lei X, de Zoete MR, Zhao J, Zheng Y, Chen H, Zhao Y, Jurado KA, Feng N, Shan L, Kluger Y, Lu J, Abraham C, Fikrig E, Greenberg HB, Flavell RA. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature 2017, 546: 667-670. PMID: 28636595, PMCID: PMC5787375, DOI: 10.1038/nature22967.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCaspase 1DEAD-box RNA HelicasesEpithelial CellsFemaleImmunity, InnateInflammasomesInterleukin-18Intestinal MucosaIntestinesIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLPhosphate-Binding ProteinsPyroptosisReceptors, G-Protein-CoupledRNA, Double-StrandedRotavirusRotavirus Infections
2015
Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor
Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J, Atteya G, Du J, Tang WH, Lee SH, Leslie K, Spollett G, Liu Z, Herzog E, Herzog RI, Lu J, Martin KA, Hwa J. Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood 2015, 125: 3377-3387. PMID: 25814526, PMCID: PMC4447857, DOI: 10.1182/blood-2015-01-620278.Peer-Reviewed Original ResearchConceptsVon Willebrand factorDiabetes mellitusMiR-24Diabetic patientsAdverse thrombotic eventsThrombotic cardiovascular eventsVWF expressionWillebrand factorDiabetic mouse modelNovel therapeutic targetHistamine H1 receptorsEndothelial cell expressionHyperglycemia-induced activationCardiovascular eventsThrombotic eventsH1 receptorsMouse modelVWF levelsTherapeutic targetCell expressionMellitusPatientsEndothelial cellsElevated levelsReactive oxygen species
2013
Dynamic Migration and Cell‐Cell Interactions of Early Reprogramming Revealed by High‐Resolution Time‐Lapse Imaging
Megyola CM, Gao Y, Teixeira AM, Cheng J, Heydari K, Cheng E, Nottoli T, Krause DS, Lu J, Guo S. Dynamic Migration and Cell‐Cell Interactions of Early Reprogramming Revealed by High‐Resolution Time‐Lapse Imaging. Stem Cells 2013, 31: 895-905. PMID: 23335078, PMCID: PMC4309553, DOI: 10.1002/stem.1323.Peer-Reviewed Original ResearchConceptsCell-cell interactionsEarly reprogrammingDynamic cell-cell interactionsSingle-cell resolutionTime-lapse microscopyE-cadherin inhibitionTime-lapse imagingPluripotency inductionInduced pluripotencyGranulocyte-monocyte progenitorsPluripotent cellsReprogrammingMolecular mechanismsCell resolutionCell migrationCellular interactionsGenetic makeupE-cadherinSatellite coloniesExperimental systemHematopoietic stateSource cellsRare cellsColoniesComplex mechanismsMicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11
Bockhorn J, Dalton R, Nwachukwu C, Huang S, Prat A, Yee K, Chang YF, Huo D, Wen Y, Swanson KE, Qiu T, Lu J, Young Park S, Eileen Dolan M, Perou CM, Olopade OI, Clarke MF, Greene GL, Liu H. MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nature Communications 2013, 4: 1393. PMID: 23340433, PMCID: PMC3723106, DOI: 10.1038/ncomms2393.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorBreast NeoplasmsCell Line, TumorCell SurvivalCluster AnalysisCytoskeletonDoxorubicinDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGATA3 Transcription FactorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInterleukin-11MiceMicrofilament ProteinsMicroRNAsPrognosisProtein-Tyrosine KinasesReal-Time Polymerase Chain ReactionSuppression, GeneticXenograft Model Antitumor AssaysConceptsMicroRNA-30cChemotherapy resistanceBreast tumorsMesenchymal transitionRelapse-free survivalBreast cancer patientsPrimary breast tumorsTumor prognostic markersTumor chemotherapy resistanceNovel therapeutic strategiesInterleukin 11 expressionCancer patientsPrognostic markerBreast cancerTherapeutic strategiesTherapy resistanceTumor progressionIL-11Interleukin-11Direct targetingTwinfilin-1TumorsChemoresistanceFamily membersMolecular mechanisms
2012
miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia
Li Z, Huang H, Chen P, He M, Li Y, Arnovitz S, Jiang X, He C, Hyjek E, Zhang J, Zhang Z, Elkahloun A, Cao D, Shen C, Wunderlich M, Wang Y, Neilly MB, Jin J, Wei M, Lu J, Valk PJ, Delwel R, Lowenberg B, Le Beau MM, Vardiman J, Mulloy JC, Zeleznik-Le NJ, Liu PP, Zhang J, Chen J. miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia. Nature Communications 2012, 3: 688. PMID: 22353710, PMCID: PMC3514459, DOI: 10.1038/ncomms1681.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBase SequenceCell Transformation, NeoplasticCells, CulturedFas ReceptorFemaleGene Expression Regulation, NeoplasticGenes, Tumor SuppressorHematopoiesisHomeodomain ProteinsHumansLeukemia, Myeloid, AcuteMaleMiceMice, Inbred C57BLMicroRNAsMyeloid Ecotropic Viral Integration Site 1 ProteinMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsSequence Analysis, DNAConceptsMiR-196bTumor suppressorMiRNA regulation mechanismOverexpression of FASBone marrow transplantationEssential oncogenic roleMiRNA regulationEctopic expressionMixed lineage leukemiaMEIS1 expressionMLL fusionsProapoptotic genesSingle miRNACell differentiationDirect targetLeukaemic phenotypeHoxa9/Meis1Marrow transplantationNormal developmentFurther repressionLeukaemic cellsOncogenic roleLineage leukemiaNormal haematopoiesisSecondary transplantation
2007
Altered microRNA expression in human heart disease
Ikeda S, Kong SW, Lu J, Bisping E, Zhang H, Allen PD, Golub TR, Pieske B, Pu WT. Altered microRNA expression in human heart disease. Physiological Genomics 2007, 31: 367-373. PMID: 17712037, DOI: 10.1152/physiolgenomics.00144.2007.Peer-Reviewed Original ResearchConceptsHeart diseaseDiagnostic groupsHuman heart failureLeft ventricular samplesHeart disease pathogenesisHeart failureIschemic cardiomyopathyDisease groupHeart functionDisease pathogenesisExpression profilesControl groupHuman heart diseaseVentricular samplesClinical diagnosisHuman left ventricular samplesContribution of microRNAsDiseaseFurther studiesImportant regulatorMultiple testingMiRNA expressionMicroRNAsExpressionGroup