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
MRTFA: A critical protein in normal and malignant hematopoiesis and beyond
Reed F, Larsuel ST, Mayday MY, Scanlon V, Krause DS. MRTFA: A critical protein in normal and malignant hematopoiesis and beyond. Journal Of Biological Chemistry 2021, 296: 100543. PMID: 33722605, PMCID: PMC8079280, DOI: 10.1016/j.jbc.2021.100543.Peer-Reviewed Original ResearchConceptsMalignant hematopoiesisActin cytoskeleton dynamicsCritical cellular functionsResponse factorSerum response factorTranscription factor ACellular rolesImmediate early genesProtein partnersTranscriptional regulationCytoskeleton dynamicsCellular functionsTranscriptional targetsTranscription factorsCytoskeletal proteinsCritical proteinsMRTFAEarly genesCell typesChromosomal translocationsHematopoietic cellsCell growthFactor AHematopoiesisMuscle cells
2019
Epithelial (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
The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification
Lu YC, Sanada C, Xavier-Ferrucio J, Wang L, Zhang PX, Grimes HL, Venkatasubramanian M, Chetal K, Aronow B, Salomonis N, Krause DS. The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell Reports 2018, 25: 2083-2093.e4. PMID: 30463007, PMCID: PMC6336197, DOI: 10.1016/j.celrep.2018.10.084.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell CycleCell LineageGene Expression RegulationGene Regulatory NetworksHEK293 CellsHigh-Throughput Nucleotide SequencingHumansMegakaryocyte-Erythroid Progenitor CellsProto-Oncogene Proteins c-mycReproducibility of ResultsSignal TransductionTranscription, GeneticTumor Suppressor Protein p53ConceptsMegakaryocytic-erythroid progenitorsCommon myeloid progenitorsTranscription factorsCell cycleSingle-cell RNA sequencingRegulatory transcription factorsMegakaryocyte-erythroid progenitorsCell cycle regulatorsCell cycle activationFate specificationLineage specificationE lineageMalignant disease statesGenetic manipulationRNA sequencingE progenitorsErythroid maturationCycle regulatorsDifferential expressionHuman cellsHealthy human cellsCycle activationMegakaryocyte progenitorsMolecular signaturesMyeloid progenitors
2017
Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages
Di Pietro C, Zhang PX, O’Rourke T, Murray TS, Wang L, Britto CJ, Koff JL, Krause DS, Egan ME, Bruscia EM. Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages. Scientific Reports 2017, 7: 10882. PMID: 28883468, PMCID: PMC5589856, DOI: 10.1038/s41598-017-11012-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytoskeletal ProteinsDisease Models, AnimalMacrophage ActivationMacrophagesMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPseudomonas aeruginosaPseudomonas InfectionsSignal TransductionToll-Like Receptor 4ConceptsCystic fibrosis transmembrane conductance regulatorPI3K/AktFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorPI3K/Akt signalingConductance regulatorAnti-bacterial immune responseAkt signalingAltered localizationEzrinCystic fibrosis diseaseMφ activationAktProtein levelsFibrosis diseaseActivationImmune regulationPhagocytosisInductionDirect linkSignalingRegulatorImmune responseMΦMacrophages
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 MAPKInfiltrationInfection
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
Reduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator
Zhang PX, Murray TS, Villella VR, Ferrari E, Esposito S, D'Souza A, Raia V, Maiuri L, Krause DS, Egan ME, Bruscia EM. Reduced Caveolin-1 Promotes Hyperinflammation due to Abnormal Heme Oxygenase-1 Localization in Lipopolysaccharide-Challenged Macrophages with Dysfunctional Cystic Fibrosis Transmembrane Conductance Regulator. The Journal Of Immunology 2013, 190: 5196-5206. PMID: 23606537, PMCID: PMC3711148, DOI: 10.4049/jimmunol.1201607.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsCaveolin 1Cells, CulturedChildChild, PreschoolCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorFemaleHeme Oxygenase-1HumansInflammationLipopolysaccharidesLung DiseasesMacrophagesMaleMembrane ProteinsMiceMice, KnockoutNasal PolypsReactive Oxygen SpeciesSignal TransductionToll-Like Receptor 4Young AdultConceptsCav-1 expressionHeme oxygenase-1Dysfunctional cystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulatorCell surfaceFibrosis transmembrane conductance regulatorProtein caveolin-1Cellular redox statusCell surface localizationCellular oxidative stateTransmembrane conductance regulatorHO-1 enzymePositive feed-forward loopCystic fibrosis macrophagesNegative regulatorCaveolin-1Conductance regulatorCell survivalHO-1 deliverySurface localizationRedox statusMΦ responsesHO-1/CO pathwayPathwayPotential target
2009
Fanconi Anemia Complementation Group FANCD2 Protein Serine 331 Phosphorylation Is Important for Fanconi Anemia Pathway Function and BRCA2 Interaction
Zhi G, Wilson JB, Chen X, Krause DS, Xiao Y, Jones NJ, Kupfer GM. Fanconi Anemia Complementation Group FANCD2 Protein Serine 331 Phosphorylation Is Important for Fanconi Anemia Pathway Function and BRCA2 Interaction. Cancer Research 2009, 69: 8775-8783. PMID: 19861535, PMCID: PMC5912675, DOI: 10.1158/0008-5472.can-09-2312.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBRCA2 ProteinCell LineCheckpoint Kinase 1DNA DamageFanconi AnemiaFanconi Anemia Complementation Group D2 ProteinFanconi Anemia Complementation Group ProteinsHumansImmunoblottingImmunoprecipitationMass SpectrometryPhosphorylationProtein KinasesSequence Homology, Amino AcidSerineSignal TransductionConceptsS-phase checkpoint kinaseFanconi anemia DNA repair pathwayFanconi anemia pathwayRegulatory phosphorylation eventsDNA repair pathwaysFANCD1/BRCA2Phosphomimetic mutationBRCA2 interactionsPhosphorylation eventsSerine 331Checkpoint kinaseCancer susceptibility syndromeComplementation groupsRepair pathwaysPathway functionFanconi anemiaBone marrow failurePhosphorylationDownstream playersVivo interactionS331Susceptibility syndromeMarrow failurePathwayMonoubiquitylation
2006
SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice
Ma Y, Cui W, Yang J, Qu J, Di C, Amin HM, Lai R, Ritz J, Krause DS, Chai L. SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice. Blood 2006, 108: 2726-2735. PMID: 16763212, PMCID: PMC1895586, DOI: 10.1182/blood-2006-02-001594.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsApoptosisBase SequenceBeta CateninCloning, MolecularColony-Forming Units AssayDNA, ComplementaryDNA, NeoplasmDNA-Binding ProteinsGene ExpressionHematopoiesisHumansLeukemia, Myeloid, AcuteMiceMice, TransgenicMyelodysplastic SyndromesNeoplasm TransplantationOncogenesProtein IsoformsRNA, MessengerRNA, NeoplasmSignal TransductionTranscription FactorsWnt ProteinsConceptsAcute myeloid leukemiaMyeloid leukemiaMurine modelTransgenic miceHuman primary acute myeloid leukemiaMDS/acute myeloid leukemiaPrimary acute myeloid leukemiaHuman acute myeloid leukemiaLeukemia stem cellsAML transformationMyelodysplastic syndromePolymerase chain reactionWnt/beta-catenin pathwayZinc finger transcriptional factorNovel oncogeneBeta-catenin pathwayLeukemogenic potentialConstitutive expressionChain reactionPathway's roleLeukemiaSALL4MiceStem cellsMouse marrow