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 colonImmunityEfficacyStingsColon
2020
The mir181ab1 cluster promotes kras-driven oncogenesis and progression in lung and pancreas
Valencia K, Erice O, Kostyrko K, Hausmann S, Guruceaga E, Tathireddy A, Flores NM, Sayles LC, Lee AG, Fragoso R, Sun TQ, Vallejo A, Roman M, Entrialgo-Cadierno R, Migueliz I, Razquin N, Fortes P, Lecanda F, Lu J, Ponz-Sarvise M, Chen CZ, Mazur PK, Sweet-Cordero EA, Vicent S. The mir181ab1 cluster promotes kras-driven oncogenesis and progression in lung and pancreas. Journal Of Clinical Investigation 2020, 130: 1879-1895. PMID: 31874105, PMCID: PMC7108928, DOI: 10.1172/jci129012.Peer-Reviewed Original ResearchConceptsPotential therapeutic targetNew molecular targetsPancreatic cancerMouse modelTherapeutic targetHuman cancer cellsDownstream effector pathwaysKRASMolecular targetsCancerCancer cellsEffector pathwaysKey modulatorNonredundant roleLungProliferative advantageProgressionUnknown roleOncogenesisPhenotypePatientsTherapyPancreasMicroRNA cluster
2017
The cationic small molecule GW4869 is cytotoxic to high phosphatidylserine‐expressing myeloma cells
Vuckovic S, Vandyke K, Rickards DA, Winter P, Brown SHJ, Mitchell TW, Liu J, Lu J, Askenase PW, Yuriev E, Capuano B, Ramsland PA, Hill GR, Zannettino ACW, Hutchinson AT. The cationic small molecule GW4869 is cytotoxic to high phosphatidylserine‐expressing myeloma cells. British Journal Of Haematology 2017, 177: 423-440. PMID: 28211573, DOI: 10.1111/bjh.14561.Peer-Reviewed Original ResearchConceptsMyeloma cell linesMyeloma cellsMyeloma plasma cellsCell linesPlasma cellsPrimary myeloma samplesMalignant cellsMyeloma samplesGW4869Surface phosphatidylserine exposurePhosphatidylserine expressionPhosphatidylserine exposureCell surface phosphatidylserine exposureCellsBiochemical analysisCytotoxicSmall cationic moleculesIntracellular sidePhosphatidylserineCancerCell membraneSmall moleculesBrefeldin A
2016
Increased miR-155-5p and reduced miR-148a-3p contribute to the suppression of osteosarcoma cell death
Bhattacharya S, Chalk AM, Ng AJ, Martin TJ, Zannettino AC, Purton LE, Lu J, Baker EK, Walkley CR. Increased miR-155-5p and reduced miR-148a-3p contribute to the suppression of osteosarcoma cell death. Oncogene 2016, 35: 5282-5294. PMID: 27041566, DOI: 10.1038/onc.2016.68.Peer-Reviewed Original ResearchConceptsMiR-148aCell deathCell biological impactMiR-155-5p inhibitionCross-species comparisonsMiR-155-5pApoptosis/necroptosisNormal osteoblastsOS cellsOsteosarcoma cell deathMurine primary osteoblastsMiRNA expression patternsMiRNA-based therapiesCell fateMiR-155-5p overexpressionExpression patternsMolecular geneticsTractable targetsPrimary osteoblastsCandidate targetsBiological impactOsteoblast culturesRIPK1MiRNAsMiRNAmiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells
Lechman ER, Gentner B, Ng SW, Schoof EM, van Galen P, Kennedy JA, Nucera S, Ciceri F, Kaufmann KB, Takayama N, Dobson SM, Trotman-Grant A, Krivdova G, Elzinga J, Mitchell A, Nilsson B, Hermans KG, Eppert K, Marke R, Isserlin R, Voisin V, Bader GD, Zandstra PW, Golub TR, Ebert BL, Lu J, Minden M, Wang JC, Naldini L, Dick JE. miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. Cancer Cell 2016, 29: 214-228. PMID: 26832662, PMCID: PMC4749543, DOI: 10.1016/j.ccell.2015.12.011.Peer-Reviewed Original ResearchConceptsLeukemia stem cellsMiR-126Human acute myeloid leukemia stem cellsAcute myeloid leukemia stem cellsMyeloid leukemia stem cellsPI3K/Akt/mTORMiR-126 expressionAkt/mTORMalignant hematopoietic stem cellsMiR-126 regulationStem cellsMiR-126 targetsLSC activityLSC quiescenceAML samplesChemotherapy resistanceHematopoietic stem cellsHematopoietic stem cell cyclingMiRNA signatureCell cycle progressionLSC functionCycle progressionStem cell cyclingSignature miRNAsCell cycling
2015
microRNA Expression Profiling: Technologies, Insights, and Prospects
Roden C, Mastriano S, Wang N, Lu J. microRNA Expression Profiling: Technologies, Insights, and Prospects. Advances In Experimental Medicine And Biology 2015, 888: 409-421. PMID: 26663195, DOI: 10.1007/978-3-319-22671-2_21.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell Line, TumorDisease Models, AnimalGene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansMicroRNAsMolecular Sequence DataNeoplasmsReverse Transcriptase Polymerase Chain ReactionSequence Homology, Nucleic AcidSignal TransductionConceptsLong small noncoding RNAsExpression profilingMiRNA isoformsMiRNA expressionProfiling technologiesDiverse biological processesSingle-cell variabilitySmall noncoding RNAsMiRNA profiling technologiesGlobal miRNA expressionNext-generation sequencingNoncoding RNAsCell variabilitySingle-molecule measurementsBiological functionsBiological processesTumor suppressorMicroRNA researchQuantitative RT-PCRCareful experimental designMiRNAsIsoformsRT-PCRProfilingExpression
2014
A Functional Screen Identifies miRs That Induce Radioresistance in Glioblastomas
Moskwa P, Zinn PO, Choi YE, Shukla SA, Fendler W, Chen CC, Lu J, Golub TR, Hjelmeland A, Chowdhury D. A Functional Screen Identifies miRs That Induce Radioresistance in Glioblastomas. Molecular Cancer Research 2014, 12: 1767-1778. PMID: 25256711, PMCID: PMC4386891, DOI: 10.1158/1541-7786.mcr-14-0268.Peer-Reviewed Original ResearchConceptsCell cycle checkpoint responsesFunctional screen identifiesTGFβ receptor inhibitorUnbiased functional screenCheckpoint responseScreen identifiesCancer Genome AtlasFunctional screenGlioblastoma patient specimensMolecular networksGlioblastoma datasetGlioblastoma cellsGenome AtlasSystematic identificationGlioblastoma radioresistanceTherapeutic resistanceMiR125aRadioresistanceTGFβNew roleTGFβ inhibitorsTherapeutic applicationsGlioblastomaMIR1MiR150
2013
MicroRNA-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
Blockade of miR-150 Maturation by MLL-Fusion/MYC/LIN-28 Is Required for MLL-Associated Leukemia
Jiang X, Huang H, Li Z, Li Y, Wang X, Gurbuxani S, Chen P, He C, You D, Zhang S, Wang J, Arnovitz S, Elkahloun A, Price C, Hong GM, Ren H, Kunjamma RB, Neilly MB, Matthews JM, Xu M, Larson RA, Le Beau MM, Slany RK, Liu PP, Lu J, Zhang J, He C, Chen J. Blockade of miR-150 Maturation by MLL-Fusion/MYC/LIN-28 Is Required for MLL-Associated Leukemia. Cancer Cell 2012, 22: 524-535. PMID: 23079661, PMCID: PMC3480215, DOI: 10.1016/j.ccr.2012.08.028.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell Transformation, NeoplasticDNA MethylationDown-RegulationFms-Like Tyrosine Kinase 3Gene DosageGene Expression Regulation, LeukemicHistone-Lysine N-MethyltransferaseHomeodomain ProteinsHumansLeukemiaMiceMicroRNAsMutationMyeloid Ecotropic Viral Integration Site 1 ProteinMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsNuclear ProteinsProto-Oncogene Proteins c-mycRNA-Binding ProteinsSignal TransductionConceptsMiR-150MiR-150 functionsLeukemic cell growthPathogenesis of leukemiaHoxa9/Meis1Acute leukemiaDysregulation of miRNAsExpression of microRNAsPivotal gatekeeperLeukemiaFunctional axisCell growthLeukemogenesisMYC/MLL fusion proteinsBlockadePathogenesisPosttranscriptional levelExpressionFusion proteinFLT3
2010
Aberrant overexpression and function of the miR-17-92 cluster in MLL-rearranged acute leukemia
Mi S, Li Z, Chen P, He C, Cao D, Elkahloun A, Lu J, Pelloso LA, Wunderlich M, Huang H, Luo RT, Sun M, He M, Neilly MB, Zeleznik-Le NJ, Thirman MJ, Mulloy JC, Liu PP, Rowley JD, Chen J. Aberrant overexpression and function of the miR-17-92 cluster in MLL-rearranged acute leukemia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 3710-3715. PMID: 20133587, PMCID: PMC2840429, DOI: 10.1073/pnas.0914900107.Peer-Reviewed Original ResearchConceptsMouse bone marrow progenitor cellsMiRNA clusterTarget genesMLL fusionsBone marrow progenitor cellsMiR-17Marrow progenitor cellsCell differentiationDNA copy number amplificationsWild-type MLLProgenitor cellsRelevant target genesHistone H3 acetylationPotential target genesMLL fusion genesCopy number amplificationDevelopment of MLLH3K4 trimethylationIndividual miRNAsH3 acetylationMixed lineage leukemiaCell cycleHuman cellsDirect bindingMiRNAs
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 dataLin28 promotes transformation and is associated with advanced human malignancies
Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S, O'Sullivan M, Lu J, Phillips LA, Lockhart VL, Shah SP, Tanwar PS, Mermel CH, Beroukhim R, Azam M, Teixeira J, Meyerson M, Hughes TP, Llovet JM, Radich J, Mullighan CG, Golub TR, Sorensen PH, Daley GQ. Lin28 promotes transformation and is associated with advanced human malignancies. Nature Genetics 2009, 41: 843-848. PMID: 19483683, PMCID: PMC2757943, DOI: 10.1038/ng.392.Peer-Reviewed Original Research
2007
MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia
Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y, Bohlander SK, Le Beau MM, Larson RA, Golub TR, Rowley JD, Chen J. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 19971-19976. PMID: 18056805, PMCID: PMC2148407, DOI: 10.1073/pnas.0709313104.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAcute lymphoblastic leukemiaLymphoblastic leukemiaAcute leukemiaMyeloid leukemiaExpression signaturesCommon acute leukemiaCommon childhood cancerCommon cytogenetic subtypeMicroRNA expression signatureNormal control samplesAcute leukemia samplesBetter prognosisChildhood cancerReal-time PCRCytogenetic subtypesMiR-223LeukemiaMiR-128aLeukemia samplesPromoter hypomethylationMiR-128MicroRNA expressionDiagnosisRegulation of expressionImpaired microRNA processing enhances cellular transformation and tumorigenesis
Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nature Genetics 2007, 39: 673-677. PMID: 17401365, DOI: 10.1038/ng2003.Peer-Reviewed Original ResearchConceptsTarget mRNA transcriptsShort hairpin RNAGlobal repressionCellular transformationMRNA transcriptsMiRNA processing machinerySmall noncoding RNAsMature miRNA expressionMiRNA lossMiRNA maturationMiRNA processingMicroRNA processingNoncoding RNAsUndifferentiated stateProcessing machineryMiRNA expressionHairpin RNAConditional deletionTumorigenesisMiRNA levelsCancer cellsTumor developmentRepressionTranscriptsRNA
2003
An adenosine analogue, IB-MECA, down-regulates estrogen receptor alpha and suppresses human breast cancer cell proliferation.
Lu J, Pierron A, Ravid K. An adenosine analogue, IB-MECA, down-regulates estrogen receptor alpha and suppresses human breast cancer cell proliferation. Cancer Research 2003, 63: 6413-23. PMID: 14559831.Peer-Reviewed Original ResearchConceptsEstrogen receptor alphaIB-MECAMCF-7 cellsReceptor alphaHuman breast cancer cell proliferationBreast cancer cell proliferationDifferent adenosine analoguesHuman breast cancer cell line MCF-7Overexpression of ERalphaBreast cancer cell line MCF-7Breast cancer treatmentCancer cell line MCF-7Adenosine analoguesHs578T cellsCancer cell proliferationCell line MCF-7Breast cancer cell typesDifferent breast cancer cell typesCancer cell typesT cellsDrug treatmentN-methyluronamideSelective agonistZR-75Positive cells