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 ResearchEvitar: designing anti-viral RNA therapies against future RNA viruses
Zhang D, Tian J, Wang Y, Lu J. Evitar: designing anti-viral RNA therapies against future RNA viruses. Bioinformatics 2022, 38: 2437-2443. PMID: 35294970, PMCID: PMC9048652, DOI: 10.1093/bioinformatics/btac144.Peer-Reviewed Original ResearchConceptsCoronavirus disease 2019 (COVID-19) pandemicSwine flu virusRNA virusesDisease 2019 pandemicRNA virus outbreaksMERS-CoV virusesPre-designed siRNAsShelf therapeuticsRespiratory virusesFlu virusVirusVirus outbreakNew RNA virusRNA therapyLack of availabilityTherapeuticsViral sequencesRNA therapeuticsSiRNAs
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
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
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
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-CellThe 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
In vivo mutagenesis of miRNA gene families using a scalable multiplexed CRISPR/Cas9 nuclease system
Narayanan A, Hill-Teran G, Moro A, Ristori E, Kasper DM, A. Roden C, Lu J, Nicoli S. In vivo mutagenesis of miRNA gene families using a scalable multiplexed CRISPR/Cas9 nuclease system. Scientific Reports 2016, 6: 32386. PMID: 27572667, PMCID: PMC5004112, DOI: 10.1038/srep32386.Peer-Reviewed Original ResearchConceptsMiRNA familiesSingle guide RNAsMiRNA gene familiesHigher multicellular organismsMultiplexed CRISPR/Entire miRNA familiesMulticellular organismsMiRNA genesGene familySame physiological functionChromosomal locationPhylogenetic ancestorsGenomic sequencesCas9 nucleaseGuide RNACRISPR/Mutagenesis strategyNuclease systemPrimary sequenceVivo mutagenesisPhysiological functionsSecondary structureModel systemMiRNAsMutationsAdenosine-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, RNA