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 colonImmunityEfficacyStingsColonSingle-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation
Wang N, Zheng J, Chen Z, Liu Y, Dura B, Kwak M, Xavier-Ferrucio J, Lu YC, Zhang M, Roden C, Cheng J, Krause DS, Ding Y, Fan R, Lu J. Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation. Nature Communications 2019, 10: 95. PMID: 30626865, PMCID: PMC6327095, DOI: 10.1038/s41467-018-07981-6.Peer-Reviewed Original ResearchConceptsSame single cellMicroRNA-mRNASingle cellsGenome-scale analysisNon-genetic cellNon-genetic heterogeneityMultiple omic profilesGenomic approachesMicroRNA regulationMolecular regulationTarget mRNAsExpression variabilityCellular pathwaysRegulatory relationshipsLevels of microRNAsIntercellular heterogeneityOmics profilesIntercellular variabilityCell heterogeneityMRNA profilesMicroRNAsMRNACellsRegulationExpressionThe 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 mutationsPri-miRNAsPrimary 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
2024
Spatially exploring RNA biology in archival formalin-fixed paraffin-embedded tissues
Bai Z, Zhang D, Gao Y, Tao B, Zhang D, Bao S, Enninful A, Wang Y, Li H, Su G, Tian X, Zhang N, Xiao Y, Liu Y, Gerstein M, Li M, Xing Y, Lu J, Xu M, Fan R. Spatially exploring RNA biology in archival formalin-fixed paraffin-embedded tissues. Cell 2024 PMID: 39353436, DOI: 10.1016/j.cell.2024.09.001.Peer-Reviewed Original ResearchRNA biologyWhole-transcriptome sequencingMicroRNA regulatory networkSplicing dynamicsDeterministic barcodingRNA speciesRNA processingRNA variantsFFPE tissuesRegulatory networksTranscriptome sequencingSpliced isoformsNon-malignant cellsTumor clonal architecturesClonal architectureGene expressionCellular dynamicsRNAArchival formalin-fixed paraffin-embedded tissueMalignant subclonesFormalin-fixed paraffin-embedded (FFPEFFPE samplesParaffin-embedded (FFPEBiologyHuman lymphomasProtocol for detecting glycoRNAs using metabolic labeling and northwestern blot
Li L, Zhang N, Pantoja C, Wang Y, Lu J. Protocol for detecting glycoRNAs using metabolic labeling and northwestern blot. STAR Protocols 2024, 5: 103321. PMID: 39298321, PMCID: PMC11426122, DOI: 10.1016/j.xpro.2024.103321.Peer-Reviewed Original ResearchWnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis
Luan Y, Hu J, Wang Q, Wang X, Li W, Qu R, Yang C, Rajendran B, Zhou H, Liu P, Zhang N, Shi Y, Liu Y, Tang W, Lu J, Wu D. Wnt5 controls splenic myelopoiesis and neutrophil functional ambivalency during DSS-induced colitis. Cell Reports 2024, 43: 113934. PMID: 38461416, PMCID: PMC11064424, DOI: 10.1016/j.celrep.2024.113934.Peer-Reviewed Original ResearchCD8<sup>+</sup> T cell activationNeutrophil productionNeutrophil plasticitySplenic extramedullary myelopoiesisFamily member 5T cell activationInnate immune cellsSplenic stromal cellsDSS-induced colitisAnti-inflammatory protectionCD101 expressionPro-inflammatory activitySplenic myelopoiesisExtramedullary myelopoiesisBone marrowImmune cellsSplenic neutrophilsMember 5Autoimmune diseasesInflammatory outcomesCell activationStromal cellsColitisSplenic productionElevated numbersPD-1H/VISTA mediates immune evasion in acute myeloid leukemia
Kim T, Han X, Hu Q, Vandsemb E, Fielder C, Hong J, Kim K, Mason E, Plowman R, Wang J, Wang Q, Zhang J, Badri T, Sanmamed M, Zheng L, Zhang T, Alawa J, Lee S, Zeidan A, Halene S, Pillai M, Chandhok N, Lu J, Xu M, Gore S, Chen L. PD-1H/VISTA mediates immune evasion in acute myeloid leukemia. Journal Of Clinical Investigation 2024, 134 PMID: 38060328, PMCID: PMC10836799, DOI: 10.1172/jci164325.Peer-Reviewed Original Research
2023
Ten-Eleven-Translocation Genes in Cancer
Wang Y, Wang X, Lu J. Ten-Eleven-Translocation Genes in Cancer. Cancer Treatment And Research 2023, 190: 363-373. PMID: 38113007, DOI: 10.1007/978-3-031-45654-1_11.Peer-Reviewed Original ResearchConceptsTET mutationsTen-ElevenBiochemical functionsTranslocation (TET) familyTranslocation geneHematopoietic malignanciesHematopoietic expansionGenesHuman cancersMutationsCritical roleImmune responseTET2Clonal hematopoiesisSolid cancersEpigenomeTET1TET3RNABiologyUnanswered questionsDNAHematopoiesisCooperateTETsCell Surface RNAs Control Neutrophil Function
Zhang N, Tang W, Torres L, Zhu L, Wang X, Ajaj Y, Wang Y, Zhang D, Kurbatov V, Zhou H, Luan Y, Kumar P, Hidalgo A, Wu D, Lu J. Cell Surface RNAs Control Neutrophil Function. Blood 2023, 142: 674. DOI: 10.1182/blood-2023-187570.Peer-Reviewed Original ResearchExtracellular RNaseCell surfaceTotal RNABona fide ligandsEndothelial cellsOuter cell surfaceTransendothelial migrationMammalian cellsSuch RNAsGlycan modificationsCellular RNAGlycoRNARNase digestionLive cellsRNAHematopoietic cellsRNase treatmentSimilar defectsIntegrin levelsConfocal microscopyRNaseGlycan fractionImportant functionsHomologuesRecombinant E-selectin
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 responseN 6-methyladenosine enhances post-transcriptional gene regulation by microRNAs
Kanoria S, Rennie WA, Carmack CS, Lu J, Ding Y. N 6-methyladenosine enhances post-transcriptional gene regulation by microRNAs. Bioinformatics Advances 2022, 2: vbab046. PMID: 35098135, PMCID: PMC8792947, DOI: 10.1093/bioadv/vbab046.Peer-Reviewed Original ResearchPost-transcriptional gene regulationMiRNA-binding sitesGene regulationMiRNA-mediated gene regulationEukaryotic messenger RNAsMiRNA-mediated regulationMiRNA-target bindingRNA-binding proteinMiRNA target sitesPost-transcriptional regulatorsPotential methylation sitesHigh GC contentHigh-throughput dataArgonaute proteinsEvolutionary conservationPrevalent modificationTarget mRNAsGC contentMethylation sitesTarget secondary structureGene expressionRNA structureSecondary structureMessenger RNAFunctional significance
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 clusterHigh-speed automatic characterization of rare events in flow cytometric data
Qi Y, Fang Y, Sinclair DR, Guo S, Alberich-Jorda M, Lu J, Tenen DG, Kharas MG, Pyne S. High-speed automatic characterization of rare events in flow cytometric data. PLOS ONE 2020, 15: e0228651. PMID: 32045462, PMCID: PMC7012421, DOI: 10.1371/journal.pone.0228651.Peer-Reviewed Original Research