2024
Ezrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAkt
2021
Methylation of dual-specificity phosphatase 4 controls cell differentiation
Su H, Jiang M, Senevirathne C, Aluri S, Zhang T, Guo H, Xavier-Ferrucio J, Jin S, Tran NT, Liu SM, Sun CW, Zhu Y, Zhao Q, Chen Y, Cable L, Shen Y, Liu J, Qu CK, Han X, Klug CA, Bhatia R, Chen Y, Nimer SD, Zheng YG, Iancu-Rubin C, Jin J, Deng H, Krause DS, Xiang J, Verma A, Luo M, Zhao X. Methylation of dual-specificity phosphatase 4 controls cell differentiation. Cell Reports 2021, 36: 109421. PMID: 34320342, PMCID: PMC9110119, DOI: 10.1016/j.celrep.2021.109421.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsArginineCell DifferentiationCell LineChildDual-Specificity PhosphatasesEnzyme StabilityFemaleHEK293 CellsHumansMaleMAP Kinase Signaling SystemMegakaryocytesMethylationMice, Inbred C57BLMiddle AgedMitogen-Activated Protein Kinase PhosphatasesMyelodysplastic SyndromesP38 Mitogen-Activated Protein KinasesPolyubiquitinProtein-Arginine N-MethyltransferasesProteolysisRepressor ProteinsUbiquitinationYoung AdultConceptsDual-specificity phosphataseCell differentiationSingle-cell transcriptional analysisP38 MAPKControls cell differentiationE3 ligase HUWE1Knockdown screeningMK differentiationTranscriptional analysisMegakaryocyte differentiationProtein kinaseP38 axisP38 activationPRMT1Transcriptional signatureContext of thrombocytopeniaMK cellsMechanistic insightsPharmacological inhibitionDifferentiationMethylationMAPKPhosphataseUbiquitinylationActivationBone Marrow-Derived VSELs Engraft as Lung Epithelial Progenitor Cells after Bleomycin-Induced Lung Injury
Ciechanowicz AK, Sielatycka K, Cymer M, Skoda M, Suszyńska M, Bujko K, Ratajczak MZ, Krause DS, Kucia M. Bone Marrow-Derived VSELs Engraft as Lung Epithelial Progenitor Cells after Bleomycin-Induced Lung Injury. Cells 2021, 10: 1570. PMID: 34206516, PMCID: PMC8303224, DOI: 10.3390/cells10071570.Peer-Reviewed Original ResearchConceptsBronchioalveolar stem cellsOrganoid assaysAT2 cellsStem cellsH2B-GFP fusion proteinLung epithelial progenitor cellsProgenitor cellsEmbryonic-like stem cellsSurfactant protein CSmall embryonic-like stem cellsEpithelial progenitor cellsLung injuryNonhematopoietic stem cellsFusion proteinAlveolar type 2 cellsPhysiological potentialProgenitor activityBleomycin-Induced Lung InjuryH2B-GFP miceWT recipient miceRegenerative functionSPC promoterType 2 cellsVSELsReporter mice
2019
A versatile flow-based assay for immunocyte-mediated cytotoxicity
Rabinovich PM, Zhang J, Kerr SR, Cheng BH, Komarovskaya M, Bersenev A, Hurwitz ME, Krause DS, Weissman SM, Katz SG. A versatile flow-based assay for immunocyte-mediated cytotoxicity. Journal Of Immunological Methods 2019, 474: 112668. PMID: 31525367, PMCID: PMC6891822, DOI: 10.1016/j.jim.2019.112668.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell NucleusCytotoxicity Tests, ImmunologicCytotoxicity, ImmunologicFlow CytometryHigh-Throughput Screening AssaysHumansImmunotherapy, AdoptiveKiller Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMelanomaMice, Inbred C57BLPredictive Value of TestsReceptors, Chimeric AntigenReproducibility of ResultsSkin NeoplasmsTime FactorsT-LymphocytesWorkflowConceptsCell-mediated cytotoxicityTumor-Infiltrating LymphocytesEffector cellsTarget cellsNK-92 cellsChimeric antigen receptorNuclear staining patternInfiltrating lymphocytesT cellsEffector nucleiFlow-based assayImmune systemFlow cytometryStaining patternAntigen receptorDead cellsKilling reactionCytotoxicityCell permeable dyeCellsAssaysCell mixturesNuclear proteinsNovel strategyCell proteinsEpithelial (E)-Cadherin is a Novel Mediator of Platelet Aggregation and Clot Stability
Scanlon VM, Teixeira AM, Tyagi T, Zou S, Zhang PX, Booth CJ, Kowalska MA, Bao J, Hwa J, Hayes V, Marks MS, Poncz M, Krause DS. Epithelial (E)-Cadherin is a Novel Mediator of Platelet Aggregation and Clot Stability. Thrombosis And Haemostasis 2019, 119: 744-757. PMID: 30861547, PMCID: PMC6599679, DOI: 10.1055/s-0039-1679908.Peer-Reviewed Original ResearchConceptsConditional knockout miceKnockout micePlatelet aggregationE-cadherinClot stabilityClot stabilizationSynthase kinase 3β activationAntibody-mediated platelet depletionVivo injury modelsNull plateletsPlatelet productionWild-type miceTail bleeding timeAkt/GSK3βMurine platelet aggregationKnockout mouse modelPlatelet dysfunctionFibrin depositionInjury modelPlatelet depletionPrimary human plateletsBleeding timeMouse modelPlatelet numberE-cadherin antibody
2018
Surfactant protein C dampens inflammation by decreasing JAK/STAT activation during lung repair
Jin H, Ciechanowicz AK, Kaplan AR, Wang L, Zhang P, Lu YC, Tobin RE, Tobin BA, Cohn L, Zeiss CJ, Lee PJ, Bruscia EM, Krause DS. Surfactant protein C dampens inflammation by decreasing JAK/STAT activation during lung repair. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 314: l882-l892. PMID: 29345196, PMCID: PMC6008135, DOI: 10.1152/ajplung.00418.2017.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeKO miceSurfactant protein CClinical acute respiratory distress syndromeProtein CAlveolar type 2 cellsAnti-inflammatory mediatorsRespiratory distress syndromeBronchoalveolar lavage fluidAnti-inflammatory moleculesPhosphorylated signal transductionType 2 cellsSPC expressionInducible suicide geneJanus kinaseLevels of suppressorDistress syndromeBAL fluidGranulocyte infiltrationJAK1/2 inhibitorLavage fluidProinflammatory phenotypeInflammatory cytokinesSevere inflammationInjury model
2017
Hematopoietic defects in response to reduced Arhgap21
Xavier-Ferrucio J, Ricon L, Vieira K, Longhini AL, Lazarini M, Bigarella CL, Franchi G, Krause DS, Saad STO. Hematopoietic defects in response to reduced Arhgap21. Stem Cell Research 2017, 26: 17-27. PMID: 29212046, PMCID: PMC6084430, DOI: 10.1016/j.scr.2017.11.014.Peer-Reviewed Original ResearchConceptsErythroid commitmentProgenitor cellsSerial bone marrow transplantationHuman primary cellsProtein familyRho GTPasesHematopoietic progenitor cellsPhenotypic HSCsRho GTPaseHematopoietic defectsRhoC activityNegative regulatorARHGAP21Hematopoietic stemHematopoietic cellsMyeloid progenitorsProgenitor coloniesPrimary cellsBone marrow cellsCancer cellsFunctional aspectsHaploinsufficient miceMarrow cellsCellsGTPasesSNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume
Zou S, Teixeira AM, Kostadima M, Astle WJ, Radhakrishnan A, Simon LM, Truman L, Fang JS, Hwa J, Zhang PX, van der Harst P, Bray PF, Ouwehand WH, Frontini M, Krause DS. SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume. PLOS ONE 2017, 12: e0178095. PMID: 28542600, PMCID: PMC5441597, DOI: 10.1371/journal.pone.0178095.Peer-Reviewed Original ResearchConceptsExpression quantitative lociMK maturationGene expressionRho guanine exchange factorsHuman megakaryocytesGenome-wide association studiesDNase I hypersensitive regionGuanine exchange factorHuman genetic studiesExchange factorReporter mouse modelDNase hypersensitivityQuantitative lociPlatelet traitsMK developmentTranscript levelsCausal SNPsHypersensitive regionARHGEF3Human phenotypesAssociation studiesGenetic studiesHematopoietic subpopulationsGenetic variantsSNPsPediatric non–Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes
de Rooij JD, Branstetter C, Ma J, Li Y, Walsh MP, Cheng J, Obulkasim A, Dang J, Easton J, Verboon LJ, Mulder HL, Zimmermann M, Koss C, Gupta P, Edmonson M, Rusch M, Lim JY, Reinhardt K, Pigazzi M, Song G, Yeoh AE, Shih LY, Liang DC, Halene S, Krause DS, Zhang J, Downing JR, Locatelli F, Reinhardt D, van den Heuvel-Eibrink MM, Zwaan CM, Fornerod M, Gruber TA. Pediatric non–Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nature Genetics 2017, 49: 451-456. PMID: 28112737, PMCID: PMC5687824, DOI: 10.1038/ng.3772.Peer-Reviewed Original Research
2016
The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation
Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-258. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DermatophagoidesAntigens, ProtozoanAsthmaBlood PlateletsCell DifferentiationCells, CulturedCytokinesExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHumansInflammationIntercellular Signaling Peptides and ProteinsLeishmania majorLeishmaniasis, CutaneousMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicModels, AnimalPyroglyphidaeSignal TransductionTh2 CellsTOR Serine-Threonine KinasesWnt ProteinsConceptsCell-mediated inflammationTh2 cell cytokine productionCell cytokine productionLeukocyte-platelet aggregatesLeukocyte infiltrationDkk-1Cytokine productionT helper 2 cellsLeishmania major infectionHouse dust miteTranscription factor c-MafAllergen challengeMajor infectionDust miteImmune responseDickkopf-1Parasitic infectionsGATA-3Pathological roleFunctional inhibitionInflammationC-MafP38 MAPKInfiltrationInfectionIncreased susceptibility of Cftr−/− mice to LPS-induced lung remodeling
Bruscia E, Zhang P, Barone C, Scholte BJ, Homer R, Krause D, Egan ME. Increased susceptibility of Cftr−/− mice to LPS-induced lung remodeling. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2016, 310: l711-l719. PMID: 26851259, PMCID: PMC4836110, DOI: 10.1152/ajplung.00284.2015.Peer-Reviewed Original ResearchConceptsLung pathologyCF miceImmune responseWT miceChronic inflammationCystic fibrosisAbnormal immune responseChronic pulmonary infectionPersistent immune responseWild-type littermatesCF mouse modelsPseudomonas aeruginosa lipopolysaccharideCF lung pathologyPulmonary infectionChronic administrationLPS exposurePersistent inflammationLung remodelingWT littermatesLung tissueOverall pathologyMouse modelInflammationChronic exposureBacterial productsLeukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation
Zou S, Teixeira AM, Yin M, Xiang Y, Xavier-Ferrucio J, Zhang PX, Hwa J, Min W, Krause DS. Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation. Thrombosis And Haemostasis 2016, 116: 506-516. PMID: 27345948, PMCID: PMC5845781, DOI: 10.1160/th15-11-0848.Peer-Reviewed Original ResearchConceptsMegakaryocyte maturationPlatelet functionRhoA activationKO plateletsLeukemia-associated Rho guanineΑ-granule releasePlatelet signal transductionSmall molecule-mediated inhibitionExchange factorSignal transductionMyosin light chain phosphorylationRho guanineKO miceBleeding timeHuman megakaryocytesInternal bleedingPlatelet aggregationNormal haemostasisLight chain phosphorylationHuman plateletsVivo assaysPlateletsSpecific roleMiceChain phosphorylation
2015
Pharmacological 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
Very Small Embryonic‐Like Stem Cells from the Murine Bone Marrow Differentiate into Epithelial Cells of the Lung
Kassmer SH, Jin H, Zhang PX, Bruscia EM, Heydari K, Lee JH, Kim CF, Kassmer SH, Krause DS. Very Small Embryonic‐Like Stem Cells from the Murine Bone Marrow Differentiate into Epithelial Cells of the Lung. Stem Cells 2013, 31: 2759-2766. PMID: 23681901, PMCID: PMC4536826, DOI: 10.1002/stem.1413.Peer-Reviewed Original ResearchConceptsEpithelial cellsSmall embryonic-like stem cellsLung epithelial cellsEmbryonic-like stem cellsStem/progenitor cellsStem cellsDonor miceHematopoietic stem/progenitor cellsBM cellsAdult BMBone marrowSmall embryonicNonhematopoietic cellsProgenitor cellsBroad differentiation potentialVSELsEngraftmentLungHigh rateNumerous reportsAdult stem cellsDifferentiation potentialCellsFirst reportReportDynamic 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 ReactionMKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation
Smith EC, Thon JN, Devine MT, Lin S, Schulz VP, Guo Y, Massaro SA, Halene S, Gallagher P, Italiano JE, Krause DS. MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation. Blood 2012, 120: 2317-2329. PMID: 22806889, PMCID: PMC3447785, DOI: 10.1182/blood-2012-04-420828.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateAnimalsBleeding TimeBlood PlateletsBone Marrow CellsCells, CulturedCrosses, GeneticCytoplasmCytoskeletonGene Expression ProfilingHematopoiesisMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisPlatelet ActivationThrombocytopeniaTrans-ActivatorsTranscription FactorsConceptsMegakaryocyte maturationPlatelet formationSerum response factorSerum response factor expressionMembrane organizationGene expressionMKL1MKL2Response factorDKO miceKO backgroundMegakaryocyte compartmentMegakaryocytesCritical roleMegakaryocyte ploidyExpressionMaturationKnockout miceFactor expressionCrucial roleHomologuesGenesMiceProlonged bleeding timeRoleNonhematopoietic Cells are the Primary Source of Bone Marrow‐Derived Lung Epithelial Cells
Kassmer SH, Bruscia EM, Zhang P, Krause DS. Nonhematopoietic Cells are the Primary Source of Bone Marrow‐Derived Lung Epithelial Cells. Stem Cells 2012, 30: 491-499. PMID: 22162244, PMCID: PMC3725285, DOI: 10.1002/stem.1003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsBone Marrow CellsBone Marrow TransplantationCell SeparationEpithelial CellsGene ExpressionLuminescent ProteinsLungMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalPulmonary Surfactant-Associated Protein CRecombinant ProteinsSingle-Cell AnalysisConceptsLung epithelial cellsNonhematopoietic cellsBM cellsEpithelial cellsBone marrowLungs of miceType 2 pneumocytesNonhematopoietic stem cellsNonhematopoietic fractionAdult BMPrimitive stem cell populationNull miceProgenitor cellsMiceStem cell populationCell populationsMarrowStem cellsMultiple tissuesHematopoietic stemBMCellsPrevious studiesEngraftmentLungProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and Platelets
Truman LA, Bentley KL, Smith EC, Massaro SA, Gonzalez DG, Haberman AM, Hill M, Jones D, Min W, Krause DS, Ruddle NH. ProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and Platelets. American Journal Of Pathology 2012, 180: 1715-1725. PMID: 22310467, PMCID: PMC3349900, DOI: 10.1016/j.ajpath.2011.12.026.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal MedullaAnimalsBlood PlateletsCells, CulturedCytoplasmEndothelial CellsGene Expression RegulationGenotypeGlycoproteinsHomeodomain ProteinsLuminescent ProteinsLymph NodesLymphatic VesselsMegakaryocytesMembrane Transport ProteinsMiceMice, Inbred C57BLMice, TransgenicMicroscopy, FluorescenceTumor Cells, CulturedTumor Suppressor ProteinsConceptsLymph nodesLymphatic vesselsAdrenal medullaExpression of Prox1Tumor metastasisHigh endothelial venulesProx1 expressionTwo-photon laser scanning microscopyTransplant rejectionDentate gyrusEndothelial venulesAntigen presentationC57BL/6 backgroundTransgenic miceLipid metabolismMiceNeuroendocrine cellsAdult liverNovel siteMetastasisMedullaStudy of diseasesLiving mouseUnknown rolePotential utility
2011
Enhanced growth and hepatic differentiation of fetal liver epithelial cells through combinational and temporal adjustment of soluble factors
Qian L, Krause DS, Saltzman WM. Enhanced growth and hepatic differentiation of fetal liver epithelial cells through combinational and temporal adjustment of soluble factors. Biotechnology Journal 2011, 7: 440-448. PMID: 21922669, PMCID: PMC3532892, DOI: 10.1002/biot.201100184.Peer-Reviewed Original Research