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
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
2018
ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates
Guan T, Dominguez CX, Amezquita RA, Laidlaw BJ, Cheng J, Henao-Mejia J, Williams A, Flavell RA, Lu J, Kaech SM. ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates. Journal Of Experimental Medicine 2018, 215: 1153-1168. PMID: 29449309, PMCID: PMC5881466, DOI: 10.1084/jem.20171352.Peer-Reviewed Original ResearchConceptsT cellsMemory CD8T cell fateMemory T cell survivalLong-term immunityT cell formationT cell survivalMiR-200 family membersGrowth factor βFamily membersTranscription factor ZEB1Effector CD8MiR-200 familyCD8Mesenchymal transitionReciprocal expression patternCell fateZEB1ZEB2Factor βCell survivalTGFCell formationUnknown genetic pathwaysCell fate decisions
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 speciesPharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation
Zhang PX, Cheng J, Zou S, D'Souza AD, Koff JL, Lu J, Lee PJ, Krause DS, Egan ME, Bruscia EM. Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation. Nature Communications 2015, 6: 6221. PMID: 25665524, PMCID: PMC4324503, DOI: 10.1038/ncomms7221.Peer-Reviewed Original ResearchConceptsCF macrophagesMiR-199aMicroRNA-199aHyper-inflammatory responseCFTR-deficient miceCystic fibrosis patientsCystic fibrosis lungLung destructionDisease morbidityPharmacological modulationCF miceCF lungFibrosis patientsInnate immunityLungMacrophagesCAV1 expressionDrug celecoxibReduced levelsTLR4CelecoxibMiceCav1PathwayMorbidity
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 mechanisms
2012
Complex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasms
Guo S, Bai H, Megyola CM, Halene S, Krause DS, Scadden DT, Lu J. Complex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16636-16641. PMID: 23012470, PMCID: PMC3478612, DOI: 10.1073/pnas.1213196109.Peer-Reviewed Original ResearchAnimalsBone Marrow CellsBone Marrow NeoplasmsBone Marrow TransplantationCell LineColony-Forming Units AssayDoxycyclineFlow CytometryGene Expression Regulation, NeoplasticGranulocyte-Macrophage Colony-Stimulating FactorInterleukin-3Leukocytes, MononuclearMiceMice, Inbred C57BLMicroRNAsMyeloproliferative DisordersOncogenesReverse Transcriptase Polymerase Chain ReactionmiR-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
2010
Lineage-Specific Transcriptional Regulation of DICER by MITF in Melanocytes
Levy C, Khaled M, Robinson KC, Veguilla RA, Chen PH, Yokoyama S, Makino E, Lu J, Larue L, Beermann F, Chin L, Bosenberg M, Song JS, Fisher DE. Lineage-Specific Transcriptional Regulation of DICER by MITF in Melanocytes. Cell 2010, 141: 994-1005. PMID: 20550935, PMCID: PMC2897150, DOI: 10.1016/j.cell.2010.05.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBcl-2-Like Protein 11Cell DifferentiationCell SurvivalCells, CulturedEpidermal CellsGene Expression RegulationGene Knockdown TechniquesHair FollicleHumansMelanocytesMembrane ProteinsMiceMice, Inbred C57BLMicrophthalmia-Associated Transcription FactorMicroRNAsPromoter Regions, GeneticProto-Oncogene ProteinsRibonuclease IIITranscription, GeneticUp-RegulationConceptsTranscriptional start siteLineage-specific transcriptional regulationDicer-dependent processingRegulatory element upstreamMITF bindsTranscriptional regulationMature miRNAsProapoptotic regulatorsMiRNA regulationStart siteMelanocyte survivalCentral regulatorDicerMelanocyte differentiationElement upstreamMiRNA expressionCell typesDicer expressionMiRNAsTranscriptional targetingMITFRegulatorMelanocytesExpressionRegulation
2009
Dicer1 functions as a haploinsufficient tumor suppressor
Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, Kirsch DG, Golub TR, Jacks T. Dicer1 functions as a haploinsufficient tumor suppressor. Genes & Development 2009, 23: 2700-2704. PMID: 19903759, PMCID: PMC2788328, DOI: 10.1101/gad.1848209.Peer-Reviewed Original ResearchConceptsHaploinsufficient tumor suppressor geneTumor suppressor geneSuppressor geneDICER1 functionHaploinsufficient tumor suppressorCopy number dataMiRNA biogenesisMiRNA processingSingle copyGenetic basisDicer1 deletionTumor suppressorInhibition of tumorigenesisHuman cancersGenesFrequent deletionsDeletionDICER1DICER1 expressionHomozygous deletionHuman tumorsAllelesReduced survivalFull lossNumber dataMicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer
Olson P, Lu J, Zhang H, Shai A, Chun MG, Wang Y, Libutti SK, Nakakura EK, Golub TR, Hanahan D. MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes & Development 2009, 23: 2152-2165. PMID: 19759263, PMCID: PMC2751988, DOI: 10.1101/gad.1820109.Peer-Reviewed Original ResearchConceptsPrimary tumorMouse modelHallmark capabilitiesPancreatic neuroendocrine tumorsAnti-angiogenic therapyTranscription factor ZEB1MiR changesMiR-200 familyMetastatic tumorsNeuroendocrine tumorsRare subsetEnhanced metastasisAngiogenesis inhibitorsMetastasisTumorsMiR signatureNeoplastic progressionHuman tumorsAltered expressionAdaptive resistanceExpression signaturesE-cadherinCancerMiRTherapyRegulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization
Popovic R, Riesbeck LE, Velu CS, Chaubey A, Zhang J, Achille NJ, Erfurth FE, Eaton K, Lu J, Grimes HL, Chen J, Rowley JD, Zeleznik-Le NJ. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood 2009, 113: 3314-3322. PMID: 19188669, PMCID: PMC2665896, DOI: 10.1182/blood-2008-04-154310.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell DifferentiationCell ProliferationCell Transformation, NeoplasticCells, CulturedEmbryonic Stem CellsGene Expression RegulationHistone-Lysine N-MethyltransferaseLeukemiaMiceMice, Inbred C57BLMicroRNAsMolecular Sequence DataMyeloid-Lymphoid Leukemia ProteinRecombinant Fusion ProteinsSequence Homology, Nucleic AcidUp-RegulationConceptsMLL fusion proteinsHox genesMiR-196bLeukemogenic MLL fusion proteinsFusion proteinEmbryonic stem cell differentiationStem cell differentiationDifferentiated hematopoietic cellsShort-term hematopoietic stem cellsMixed lineage leukemia (MLL) geneBone marrow progenitor cellsLeukemia developmentHOXA clusterHematopoietic stem cellsPrimary leukemia samplesChimeric proteinMarrow progenitor cellsHematopoietic lineagesCell differentiationLeukemia geneFusion contributesChromosomal translocationsHematopoietic cellsGenesStem cells
2008
ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling
Hartner JC, Walkley CR, Lu J, Orkin SH. ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nature Immunology 2008, 10: 109-115. PMID: 19060901, PMCID: PMC2701568, DOI: 10.1038/ni.1680.Peer-Reviewed Original ResearchMicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors
Lu J, Guo S, Ebert BL, Zhang H, Peng X, Bosco J, Pretz J, Schlanger R, Wang JY, Mak RH, Dombkowski DM, Preffer FI, Scadden DT, Golub TR. MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors. Developmental Cell 2008, 14: 843-853. PMID: 18539114, PMCID: PMC2688789, DOI: 10.1016/j.devcel.2008.03.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD34Bone Marrow CellsCell DifferentiationCell LineageCells, CulturedErythroid CellsErythropoietinGene Expression RegulationGenes, ReporterHematopoietic Stem CellsHumansIntegrin beta3K562 CellsMegakaryocytesMiceMice, Inbred C57BLMicroRNAsModels, BiologicalPlatelet Membrane Glycoprotein IIbProto-Oncogene Proteins c-mybThrombopoietinConceptsMegakaryocyte-erythrocyte progenitorsLineage specificationTranscription factor MYBMiR-150Cell fateLineage fateRegenerative biologyErythroid cellsFunction experimentsMultipotent cellsMegakaryocytic lineageMiRNA expressionPrimary cellsCritical targetModel systemMicroRNAsProgenitorsFateRegulationCellsImportant participantsMYBLineagesMiRNAsBiology