Featured Publications
Cell surface RNAs control neutrophil recruitment
Zhang N, Tang W, Torres L, Wang X, Ajaj Y, Zhu L, Luan Y, Zhou H, Wang Y, Zhang D, Kurbatov V, Khan S, Kumar P, Hidalgo A, Wu D, Lu J. Cell surface RNAs control neutrophil recruitment. Cell 2024, 187: 846-860.e17. PMID: 38262409, PMCID: PMC10922858, DOI: 10.1016/j.cell.2023.12.033.Peer-Reviewed Original ResearchConceptsCell surfaceMammalian homologOuter cell surfaceRNA transportGlycan modificationsMammalian cellsSID-1Cellular functionsRecruitment to inflammatory sitesGlycoRNARNAMurine neutrophilsFunctional significanceNeutrophil recruitmentNeutrophil recruitment to inflammatory sitesBiological importanceCellsNeutrophil adhesionReduced neutrophil adhesionHomologyGlycansGenesInflammatory sitesRecruitmentEndothelial cells5‐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 malignanciesMalignancyTET2Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation
Roden C, Gaillard J, Kanoria S, Rennie W, Barish S, Cheng J, Pan W, Liu J, Cotsapas C, Ding Y, Lu J. Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation. Genome Research 2017, 27: 374-384. PMID: 28087842, PMCID: PMC5340965, DOI: 10.1101/gr.208900.116.Peer-Reviewed Original ResearchConceptsPri-miRNA processingHuman genetic variationGenetic variationPrimary sequence motifsPrimary microRNA processingMiRNA biogenesisDisease-causing mutationsPrimary miRNAsPri-miRNAsSequence motifsMiRNA hairpinsMicroRNA processingMature microRNAsSequence featuresRNA hairpinsComputational pipelineNovel determinantStem lengthUnpaired basesHairpinTranscriptsStemBiogenesisGenomeMiRNAsA Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions
Cheng J, Roden CA, Pan W, Zhu S, Baccei A, Pan X, Jiang T, Kluger Y, Weissman SM, Guo S, Flavell RA, Ding Y, Lu J. A Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions. Nature Communications 2016, 7: 11178. PMID: 27025950, PMCID: PMC4820989, DOI: 10.1038/ncomms11178.Peer-Reviewed Original ResearchAnimalsBacterial ProteinsCell LineChromosome MappingCloning, MolecularClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9DNADNA Restriction EnzymesEndonucleasesGene LibraryGenomeHumansMiceMicroRNAsOligonucleotide Array Sequence AnalysisRNA, Guide, CRISPR-Cas SystemsUntranslated RegionsmiR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanism
Liu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, Roden C, Pan W, Khan S, Chen S, Kyba M, Fan R, Guo S, Lu J. miR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanism. Blood 2017, 129: 1491-1502. PMID: 28053194, PMCID: PMC5356452, DOI: 10.1182/blood-2016-06-721027.Peer-Reviewed Original Research
2020
Resolving Cell Cycle Speed in One Snapshot with a Live-Cell Fluorescent Reporter
Eastman AE, Chen X, Hu X, Hartman AA, Morales A, Yang C, Lu J, Kueh HY, Guo S. Resolving Cell Cycle Speed in One Snapshot with a Live-Cell Fluorescent Reporter. Cell Reports 2020, 31: 107804. PMID: 32579930, PMCID: PMC7418154, DOI: 10.1016/j.celrep.2020.107804.Peer-Reviewed Original ResearchConceptsFluorescent reportersLive-cell fluorescent reporterCell cycle speedFluorescent timer proteinsCell proliferationCell cycle dynamicsRed fluorescent proteinFaster cycling cellsFate transitionsFusion reporterActive lociTimer proteinFluorescent proteinLength heterogeneityComplex tissuesHematopoietic cellsCycling cellsReporterFluorescence ratioCycle dynamicsProteinFunctional heterogeneityMouse strainsSolid tissuesCycle speedThe 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
2019
MKL1-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
Capture, amplification, and global profiling of microRNAs from low quantities of whole cell lysate
Wang N, Cheng J, Fan R, Lu J. Capture, amplification, and global profiling of microRNAs from low quantities of whole cell lysate. Analyst 2017, 142: 3203-3211. PMID: 28765841, PMCID: PMC5605290, DOI: 10.1039/c7an00670e.Peer-Reviewed Original ResearchConceptsWhole cell lysatesSmall non-coding RNAsComplex regulatory networkMiRNA profilingCell lysatesPost-transcriptional levelIsogenic cell linesNon-coding RNAsAdaptor ligationLow quantity samplesGenome scaleRegulatory networksGlobal profilingMiRNA captureGene expressionExpression profilesHuman diseasesMiRNA expressionLibrary preparationMiRNA alterationsCell typesMiRNA releaseRNA purificationMulti-step purificationCell linesNlrp9b 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 InfectionsThe microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection
Moffett HF, Cartwright ANR, Kim HJ, Godec J, Pyrdol J, Äijö T, Martinez GJ, Rao A, Lu J, Golub TR, Cantor H, Sharpe AH, Novina CD, Wucherpfennig KW. The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nature Immunology 2017, 18: 791-799. PMID: 28530712, PMCID: PMC5753758, DOI: 10.1038/ni.3755.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralArenaviridae InfectionsCalciumCD8-Positive T-LymphocytesChromatin ImmunoprecipitationCytokinesDendritic CellsEnzyme-Linked Immunosorbent AssayFlow CytometryGene Expression ProfilingImmunoblottingInterferon Type ILymphocytic choriomeningitis virusMiceMice, KnockoutMicroRNAsNFATC Transcription FactorsReal-Time Polymerase Chain ReactionReceptors, Antigen, T-Cell
2016
Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis
Liddicoat BJ, Hartner JC, Piskol R, Ramaswami G, Chalk AM, Kingsley PD, Sankaran VG, Wall M, Purton LE, Seeburg PH, Palis J, Orkin SH, Lu J, Li JB, Walkley CR. Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis. Experimental Hematology 2016, 44: 947-963. PMID: 27373493, PMCID: PMC5035604, DOI: 10.1016/j.exphem.2016.06.250.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine DeaminaseAnimalsCluster AnalysisErythrocyte IndicesErythroid CellsErythropoiesisGene ExpressionGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Knockout TechniquesGranulocytesHematopoietic Stem Cell TransplantationInosineInterferonsMiceMicroRNAsMyelopoiesisOrgan SpecificityPhenotypeReceptors, InterferonRetroelementsRNA EditingRNA-Binding ProteinsSignal TransductionTranscription, GeneticConceptsRNA editingErythroid cellsNormal erythropoiesisHematopoietic stem/progenitorsHematopoietic cell typesInnate immune signalingStem/progenitorsEditing eventsErythroid-specific transcriptsEssential functionsImmune signalingMurine erythropoiesisADAR1Cell deathCell typesMyeloid-restricted deletionEditingRNAMicroRNA levelsErythropoiesisCellsProfound activationTranscriptsSignalingAdenosineIncreased 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 culturesRIPK1MiRNAsMiRNAThe microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity
Gonzalez-Martin A, Adams BD, Lai M, Shepherd J, Salvador-Bernaldez M, Salvador JM, Lu J, Nemazee D, Xiao C. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity. Nature Immunology 2016, 17: 433-440. PMID: 26901150, PMCID: PMC4803625, DOI: 10.1038/ni.3385.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisApoptosis Regulatory ProteinsAutoimmunityBcl-2-Like Protein 11B-LymphocytesBone Marrow TransplantationCell Cycle ProteinsCell ProliferationDisease Models, AnimalHEK293 CellsHumansImmune ToleranceImmunoblottingLupus Erythematosus, SystemicMembrane ProteinsMiceMice, Inbred MRL lprMicroRNAsNuclear ProteinsProto-Oncogene ProteinsPTEN PhosphohydrolaseReverse Transcriptase Polymerase Chain ReactionSequence Analysis, RNAmiR-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
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 speciesCharacterization of the mammalian miRNA turnover landscape
Guo Y, Liu J, Elfenbein SJ, Ma Y, Zhong M, Qiu C, Ding Y, Lu J. Characterization of the mammalian miRNA turnover landscape. Nucleic Acids Research 2015, 43: 2326-2341. PMID: 25653157, PMCID: PMC4344502, DOI: 10.1093/nar/gkv057.Peer-Reviewed Original ResearchConceptsMiRNA turnoverStable small RNAsMammalian cell typesCultured mammalian cellsSubset of miRNAsTurnover kineticsMiRNA biogenesisMost miRNAsMiR-222-5pNucleotide biasSmall RNAsMiRNA maturationMammalian cellsSame miRNAMiRNA poolExpression profilingHsp90 associationSequence determinantsDeep sequencingHsp90 inhibitionTurnover rateMiRNA isoformsDifferent turnover ratesSequence featuresCell types
2014
STarMir: a web server for prediction of microRNA binding sites
Rennie W, Liu C, Carmack CS, Wolenc A, Kanoria S, Lu J, Long D, Ding Y. STarMir: a web server for prediction of microRNA binding sites. Nucleic Acids Research 2014, 42: w114-w118. PMID: 24803672, PMCID: PMC4086099, DOI: 10.1093/nar/gku376.Peer-Reviewed Original ResearchNonstochastic Reprogramming from a Privileged Somatic Cell State
Guo S, Zi X, Schulz VP, Cheng J, Zhong M, Koochaki SH, Megyola CM, Pan X, Heydari K, Weissman SM, Gallagher PG, Krause DS, Fan R, Lu J. Nonstochastic Reprogramming from a Privileged Somatic Cell State. Cell 2014, 156: 649-662. PMID: 24486105, PMCID: PMC4318260, DOI: 10.1016/j.cell.2014.01.020.Peer-Reviewed Original ResearchConceptsSomatic cell stateCell statesAcquisition of pluripotencyMurine hematopoietic progenitorsEndogenous Oct4Cell cycle accelerationNonstochastic mannerSomatic cellsProgeny cellsPluripotent fateYamanaka factorsCell cycleHematopoietic progenitorsP53 knockdownPluripotencyReprogrammingCycling populationFactor expressionCellsFibroblastsImportant bottleneckKnockdownProgenitorsFateExpression