2024
Enhancing 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 ResearchConceptsPoly(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
2022
Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis
Öz H, Cheng E, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang P, Huang P, Esquibies S, Britto C, Schupp J, Murray T, Halene S, Krause D, Egan M, Bruscia E. Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis. Cell Reports 2022, 41: 111797. PMID: 36516754, PMCID: PMC9833830, DOI: 10.1016/j.celrep.2022.111797.Peer-Reviewed Original ResearchConceptsC motif chemokine receptor 2Monocytes/macrophagesLung tissue damageCystic fibrosisTissue damageCF lungPulmonary neutrophilic inflammationPro-inflammatory environmentChemokine receptor 2CF lung diseaseNumber of monocytesSpecific therapeutic agentsGrowth factor βCF transmembrane conductance regulatorLung hyperinflammationLung neutrophiliaNeutrophilic inflammationNeutrophil inflammationInflammation contributesLung damageNeutrophil recruitmentLung diseaseLung tissueReceptor 2Therapeutic targetRecruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis
Di Pietro C, Öz HH, Zhang PX, Cheng EC, Martis V, Bonfield TL, Kelley TJ, Jubin R, Abuchowski A, Krause DS, Egan ME, Murray TS, Bruscia EM. Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis. Experimental & Molecular Medicine 2022, 54: 639-652. PMID: 35581352, PMCID: PMC9166813, DOI: 10.1038/s12276-022-00770-8.Peer-Reviewed Original ResearchConceptsHeme oxygenase-1Cystic fibrosisOxygenase-1Myeloid differentiation factor 88Neutrophilic pulmonary inflammationChronic airway infectionDifferentiation factor 88HO-1 levelsDisease mouse modelPseudomonas aeruginosaRecruitment of monocytesResolution of inflammationMonocytes/macrophagesTreatment of CFConditional knockout miceMechanism of actionLung neutrophiliaNeutrophilic inflammationLung inflammationAirway infectionPulmonary diseasePulmonary inflammationFactor 88Lung damageProinflammatory cytokines
2021
Nanoparticles for delivery of agents to fetal lungs
Ullrich SJ, Freedman-Weiss M, Ahle S, Mandl HK, Piotrowski-Daspit AS, Roberts K, Yung N, Maassel N, Bauer-Pisani T, Ricciardi AS, Egan ME, Glazer PM, Saltzman WM, Stitelman DH. Nanoparticles for delivery of agents to fetal lungs. Acta Biomaterialia 2021, 123: 346-353. PMID: 33484911, PMCID: PMC7962939, DOI: 10.1016/j.actbio.2021.01.024.Peer-Reviewed Original ResearchConceptsFetal lungCellular uptakeIntra-amniotic routeRoute of deliveryCongenital lung diseaseDelivery of agentsIntra-amniotic deliveryRelative cellular uptakeNanoparticlesFetal treatmentDiaphragmatic herniaLung diseaseFetal therapyLung tissueFetal miceIntravenous deliveryCystic fibrosisLungLung therapyInterventional technologiesTherapeutic agentsEndothelial cellsCell populationsEffective targetingTherapy
2020
Global chemical effects of the microbiome include new bile-acid conjugations
Quinn RA, Melnik AV, Vrbanac A, Fu T, Patras KA, Christy MP, Bodai Z, Belda-Ferre P, Tripathi A, Chung LK, Downes M, Welch RD, Quinn M, Humphrey G, Panitchpakdi M, Weldon KC, Aksenov A, da Silva R, Avila-Pacheco J, Clish C, Bae S, Mallick H, Franzosa EA, Lloyd-Price J, Bussell R, Thron T, Nelson AT, Wang M, Leszczynski E, Vargas F, Gauglitz JM, Meehan MJ, Gentry E, Arthur TD, Komor AC, Poulsen O, Boland BS, Chang JT, Sandborn WJ, Lim M, Garg N, Lumeng JC, Xavier RJ, Kazmierczak BI, Jain R, Egan M, Rhee KE, Ferguson D, Raffatellu M, Vlamakis H, Haddad GG, Siegel D, Huttenhower C, Mazmanian SK, Evans RM, Nizet V, Knight R, Dorrestein PC. Global chemical effects of the microbiome include new bile-acid conjugations. Nature 2020, 579: 123-129. PMID: 32103176, PMCID: PMC7252668, DOI: 10.1038/s41586-020-2047-9.Peer-Reviewed Original ResearchConceptsChemical interactionChemistryBile acid synthesis genesChemical effectsInflammatory bowel diseaseBile acid conjugatesCompoundsHost bile acidsMolecular familiesBile acid conjugationBowel diseaseGut diseasesMicrobiome dysbiosisConjugationAcidFree miceAmino acid conjugationBile acidsCystic fibrosisX receptorAcid conjugationReduced expressionFurther studiesDiseaseMice
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
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
2011
Calcium-Modulated Chloride Pathways Contribute to Chloride Flux in Murine Cystic Fibrosis-Affected Macrophages
Shenoy A, Kopic S, Murek M, Caputo C, Geibel JP, Egan ME. Calcium-Modulated Chloride Pathways Contribute to Chloride Flux in Murine Cystic Fibrosis-Affected Macrophages. Pediatric Research 2011, 70: 447-452. PMID: 21796019, PMCID: PMC3189336, DOI: 10.1203/pdr.0b013e31822f2448.Peer-Reviewed Original ResearchConceptsCystic fibrosisWT macrophagesCF macrophagesExtracellular Ca2CAMP-activated chloride channelCystic fibrosis transmembrane conductance regulator (CFTR) proteinContribution of CFTRIon transport abnormalitiesResult of mutationsContribution of calciumRegulator proteinRobust inflammationChronic infectionMacrophage dysfunctionMacrophage functionIntracellular Ca2Transport abnormalitiesMacrophagesChloride channelsMethoxy-quinolinium bromideCFTRinh-172Fluorescent indicator dyesFibrosisPathwayCFTRAbnormal Trafficking and Degradation of TLR4 Underlie the Elevated Inflammatory Response in Cystic Fibrosis
Bruscia EM, Zhang PX, Satoh A, Caputo C, Medzhitov R, Shenoy A, Egan ME, Krause DS. Abnormal Trafficking and Degradation of TLR4 Underlie the Elevated Inflammatory Response in Cystic Fibrosis. The Journal Of Immunology 2011, 186: 6990-6998. PMID: 21593379, PMCID: PMC3111054, DOI: 10.4049/jimmunol.1100396.Peer-Reviewed Original Research
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
2008
Macrophages Directly Contribute to the Exaggerated Inflammatory Response in Cystic Fibrosis Transmembrane Conductance Regulator−/− Mice
Bruscia EM, Zhang PX, Ferreira E, Caputo C, Emerson JW, Tuck D, Krause DS, Egan ME. Macrophages Directly Contribute to the Exaggerated Inflammatory Response in Cystic Fibrosis Transmembrane Conductance Regulator−/− Mice. American Journal Of Respiratory Cell And Molecular Biology 2008, 40: 295-304. PMID: 18776130, PMCID: PMC2645527, DOI: 10.1165/rcmb.2008-0170oc.Peer-Reviewed Original ResearchConceptsExaggerated inflammatory responseExaggerated immune responseBone marrow-derived macrophagesIL-6Marrow-derived macrophagesCystic fibrosisCF miceKeratinocyte chemoattractantCytokine responsesInflammatory responseIL-1alphaImmune responseAlveolar macrophagesBronchoalveolar lavage fluidGranulocyte colony-stimulating factorNumber of neutrophilsChemoattractant protein-1CF lung diseaseElevated cytokine responseInnate immune systemImportant therapeutic targetCF mouse modelsPopulation of macrophagesColony-stimulating factorPseudomonas aeruginosa LPSRectal Potential Difference and the Functional Expression of CFTR in the Gastrointestinal Epithelia in Cystic Fibrosis Mouse Models
Weiner SA, Caputo C, Bruscia E, Ferreira EC, Price JE, Krause DS, Egan ME. Rectal Potential Difference and the Functional Expression of CFTR in the Gastrointestinal Epithelia in Cystic Fibrosis Mouse Models. Pediatric Research 2008, 63: 73-78. PMID: 18043508, DOI: 10.1203/pdr.0b013e31815b4bc6.Peer-Reviewed Original ResearchConceptsRectal potential differenceMouse modelCF mouse modelsCystic fibrosisFibrosis mouse modelDifferent mouse modelsCystic fibrosis mouse modelUssing chamber methodEffects of interventionsAutosomal recessive diseasePharmacologic interventionsRespiratory epitheliumElectrophysiologic phenotypeGastrointestinal epitheliumCF transmembrane conductance regulator (CFTR) geneRecessive diseaseVivo methodsVivo assaysVivo dataCFTR functionTransmembrane conductance regulator geneReliable assayEpitheliumInterventionCFTR expression
2006
ΔF508 Mutation Results in Impaired Gastric Acid Secretion*
Sidani SM, Kirchhoff P, Socrates T, Stelter L, Ferreira E, Caputo C, Roberts KE, Bell RL, Egan ME, Geibel JP. ΔF508 Mutation Results in Impaired Gastric Acid Secretion*. Journal Of Biological Chemistry 2006, 282: 6068-6074. PMID: 17178714, DOI: 10.1074/jbc.m608427200.Peer-Reviewed Original ResearchConceptsCystic fibrosis transmembrane conductance regulatorATP-binding cassette (ABC) transportersFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorMouse gastric glandsParietal cellsMultifunctional proteinCFTR proteinRegulatory proteinsTransport proteinsCassette transportersConductance regulatorRegulatory roleApical poleSecretagogue-induced acid secretionGland lumenGastric glandsSulfonylurea receptorProteinImpaired gastric acid secretionK-ATPaseCl(-) secretionImmunofluorescent localizationCl- channelsATP-sensitive potassium channelsEngraftment 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 marrowAssessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation
Bruscia EM, Price JE, Cheng EC, Weiner S, Caputo C, Ferreira EC, Egan ME, Krause DS. Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 2965-2970. PMID: 16481627, PMCID: PMC1413802, DOI: 10.1073/pnas.0510758103.Peer-Reviewed Original ResearchConceptsCftr-/- miceEpithelial cellsNasal epitheliumBM-derived cellsBone marrow transplantationWild-type BMAirway epithelial cellsCystic fibrosis transmembrane conductance regulator (CFTR) activityCystic fibrosis miceRare epithelial cellsCftr-null miceMarrow transplantationBM transplantationFibrosis miceRespiratory tractCFTR activityGI tractBone marrowGastrointestinalChloride secretionCFTR-dependent chloride secretionIndividual miceTransplantationDifferent dosesMice
2004
Curcumin, a Major Constituent of Turmeric, Corrects Cystic Fibrosis Defects
Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glöckner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ. Curcumin, a Major Constituent of Turmeric, Corrects Cystic Fibrosis Defects. Science 2004, 304: 600-602. PMID: 15105504, DOI: 10.1126/science.1093941.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCalnexinCell LineCell MembraneCricetinaeCurcuminCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorElectrolytesEndoplasmic ReticulumGene TargetingGlycosylationHumansIntestinal MucosaIntestinal ObstructionIsoproterenolMembrane PotentialsMiceMice, KnockoutMutationNasal MucosaPolyethylene GlycolsProtein FoldingRectumTransfectionConceptsCystic fibrosis transmembrane conductance regulatorCFTR proteinDeltaF508 cystic fibrosis transmembrane conductance regulatorDeltaF508 CFTR proteinFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorBaby hamster kidney cellsPlasma membraneComplete knockoutConductance regulatorHamster kidney cellsEndoplasmic reticulumCystic fibrosis defectCFTR geneKidney cellsCFTR miceGenesProteinMutationsCommon mutationsHomozygous expressionCurcumin treatmentFunctional appearanceWeight basisRegulator
1999
CFTR is functionally active in GnRH-expressing GT1–7 hypothalamic neurons
Weyler R, Yurko-Mauro K, Rubenstein R, Kollen W, Reenstra W, Altschuler S, Egan M, Mulberg A. CFTR is functionally active in GnRH-expressing GT1–7 hypothalamic neurons. American Journal Of Physiology 1999, 277: c563-c571. PMID: 10484343, DOI: 10.1152/ajpcell.1999.277.3.c563.Peer-Reviewed Original ResearchConceptsGT1-7 hypothalamic neuronsHypothalamic neuronsHypothalamic neuronal cell lineGonadotropin-releasing hormoneGT1-7 cellsNeuronal cell linePreincubation of cellsGnRH secretionGT1-7Cystic fibrosisCFTR geneWestern blottingCystic fibrosis transmembrane conductance regulator (CFTR) geneCell linesGnRHDiverse manifestationsHuman brainNeuronsCAMP analogTransmembrane conductance regulator geneSexual differentiationExon 10CFTR activity
1998
[49] Assays of dynamics, mechanisms, and regulation of ATP transport and release: Implications for study of ABC transporter function
Schwiebert E, Egan M, Guggino W. [49] Assays of dynamics, mechanisms, and regulation of ATP transport and release: Implications for study of ABC transporter function. Methods In Enzymology 1998, 292: 664-675. PMID: 9711590, DOI: 10.1016/s0076-6879(98)92051-1.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAdenosine TriphosphateAnimalsATP-Binding Cassette TransportersCells, CulturedColforsinCystic Fibrosis Transmembrane Conductance RegulatorElectrophysiologyEpithelial CellsHumansIonomycinLuminescent MeasurementsMembrane PotentialsMiceModels, BiologicalOocytesOsmolar ConcentrationPatch-Clamp TechniquesSignal TransductionTritiumConceptsCystic fibrosis transmembrane conductance regulatorABC transportersATP-binding cassette (ABC) transportersSulfonylurea receptorFibrosis transmembrane conductance regulatorTransport of ATPABC transporter functionTransmembrane conductance regulatorImportance of ATPRegulatory machineryPancreatic β-cellsATP transportCassette transportersConductance regulatorTransporter functionTransporter moleculesBiological significanceATP sensorATPAgonist functionTransportersRelease of ATPΒ-cellsPowerful approachRegulator