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 recruitmentProteinAktEnhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys
Piotrowski-Daspit A, Bracaglia L, Eaton D, Richfield O, Binns T, Albert C, Gould J, Mortlock R, Egan M, Pober J, Saltzman W. Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys. Nature Communications 2024, 15: 4247. PMID: 38762483, PMCID: PMC11102454, DOI: 10.1038/s41467-024-48442-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDrug Delivery SystemsFemaleHumansMacrophagesMiceMice, Inbred C57BLNanoparticlesPolymersTissue DistributionConceptsPoly(amine-co-esterPolymer nanoparticlesDelivery of nucleic acid therapeuticsCell-type tropismTissue tropismNucleic acid delivery vehiclesIn vivo deliveryIn vivo efficacyCirculation half-lifeNucleic acid therapeuticsVehicle characteristicsTunable propertiesBiodistribution assessmentPhysiological fatePolymer chemistrySurface propertiesPharmacokinetic modelTissue targetingNanoparticlesDistribution modifiersPolymeric nanoparticlesTropismPolymerDelivery vehiclesHalf-life
2016
Increased 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 products
2015
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium
McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME. Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nature Communications 2015, 6: 6952. PMID: 25914116, PMCID: PMC4480796, DOI: 10.1038/ncomms7952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsGenetic TherapyHigh-Throughput Nucleotide SequencingHumansLactic AcidMice, Inbred C57BLNanoparticlesPeptide Nucleic AcidsPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPolymersRespiratory MucosaConceptsFacile genome engineeringVivo gene deliveryBiodegradable polymer nanoparticlesTransient gene expressionNanoparticle systemsGene deliveryPolymer nanoparticlesGene correctionGenome engineeringNanoparticlesOff-target effectsPeptide nucleic acidLethal genetic disorderNucleic acidsDonor DNATarget effectsIntranasal deliveryDeliveryCystic fibrosisEngineeringOligonucleotideChloride effluxHuman cellsAirway epitheliumLung tissuePharmacological 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
2009
Partial Correction of Cystic Fibrosis Defects with PLGA Nanoparticles Encapsulating Curcumin
Cartiera MS, Ferreira EC, Caputo C, Egan ME, Caplan MJ, Saltzman WM. Partial Correction of Cystic Fibrosis Defects with PLGA Nanoparticles Encapsulating Curcumin. Molecular Pharmaceutics 2009, 7: 86-93. PMID: 19886674, PMCID: PMC2815009, DOI: 10.1021/mp900138a.Peer-Reviewed Original ResearchAdministration, OralAnimalsBiological AvailabilityBiological Transport, ActiveCurcuminCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEnzyme InhibitorsHumansLactic AcidMiceMice, Inbred C57BLMice, Inbred CFTRMicroscopy, Electron, ScanningMutationNanoparticlesPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerSarcoplasmic Reticulum Calcium-Transporting ATPases
2006
Engraftment of Donor‐Derived Epithelial Cells in Multiple Organs Following Bone Marrow Transplantation into Newborn Mice
Bruscia EM, Ziegler EC, Price JE, Weiner S, Egan ME, Krause DS. Engraftment of Donor‐Derived Epithelial Cells in Multiple Organs Following Bone Marrow Transplantation into Newborn Mice. Stem Cells 2006, 24: 2299-2308. PMID: 16794262, DOI: 10.1634/stemcells.2006-0166.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBone Marrow TransplantationCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsFemaleFluorescent Antibody TechniqueHematopoietic Stem Cell TransplantationIn Situ Hybridization, FluorescenceMaleMiceMice, Inbred C57BLMice, Inbred StrainsMice, TransgenicRNA, MessengerY ChromosomeConceptsBone marrow-derived cellsMarrow-derived epithelial cellsBone marrow transplantationNewborn miceEpithelial cellsMarrow transplantationGI tractBone marrow-derived epithelial cellsDonor-derived epithelial cellsDoses of busulfanMarrow-derived cellsEngraftment of donorIrradiated adult recipientsMyeloablative regimenPreparative regimenAdult recipientsDifferent regimensEngrafted miceHematopoietic engraftmentGastrointestinal tractSurvival advantageTherapeutic benefitAdult miceMultiple organsBone marrow