2024
Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation
Gupta A, Barone C, Quijano E, Piotrowski-Daspit A, Perera J, Riccardi A, Jamali H, Turchick A, Zao W, Saltzman W, Glazer P, Egan M. Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation. Journal Of Cystic Fibrosis 2024 PMID: 39107154, DOI: 10.1016/j.jcf.2024.07.009.Peer-Reviewed Original ResearchCystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulator geneF508del-CFTR mutationPeptide nucleic acidCFBE cellsBronchial epithelial cellsCystic fibrosisTriplex-forming peptide nucleic acidsDonor DNACFTR mutationsEpithelial cellsCFTR functionMutations associated with genetic diseasesPrimary nasal epithelial cellsAnalysis of genomic DNAGenetic diseasesIncreased CFTR functionDevelopment of peptide nucleic acidsImprove CFTR functionTransmembrane conductance regulatorAutosomal recessive genetic diseaseNasal epithelial cellsAir-liquid interfaceCystic fibrosis bronchial epithelial cellsHuman bronchial epithelial cellsEnhancing 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-lifeUnderstanding Impact of CFTR Dysfunction on Airway Immune Cell Composition in Early Lung Disease Pathogenesis
Kockar Kizilirmak T, Yin H, Garrison A, Bruscia E, Egan M, Britto-Leon C. Understanding Impact of CFTR Dysfunction on Airway Immune Cell Composition in Early Lung Disease Pathogenesis. 2024, a6357-a6357. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6357.Peer-Reviewed Original ResearchDe-labeling of Food Allergy in Electronic Medical Records for Cystic Fibrosis Patients to Avoid Unnecessary Food Restriction
Nguyen H, Bruscia E, Young J, Egan M, Leeds S. De-labeling of Food Allergy in Electronic Medical Records for Cystic Fibrosis Patients to Avoid Unnecessary Food Restriction. Journal Of Allergy And Clinical Immunology 2024, 153: ab114. DOI: 10.1016/j.jaci.2023.11.376.Peer-Reviewed Original Research
2023
194 Investigating the role of bromodomain-containing 8 isoforms in the innate immune response of human airway epithelial cells
Browne J, Bruscia E, Garrison A, Harris A, Egan M. 194 Investigating the role of bromodomain-containing 8 isoforms in the innate immune response of human airway epithelial cells. Journal Of Cystic Fibrosis 2023, 22: s101. DOI: 10.1016/s1569-1993(23)01124-4.Peer-Reviewed Original ResearchHemoptysis in the Time of COVID
Kockar Kizilirmak T, Brumer E, Panacherry S, Egan M. Hemoptysis in the Time of COVID. 2023, a1928-a1928. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a1928.Peer-Reviewed Original ResearchFuture therapies for cystic fibrosis
Allen L, Allen L, Carr S, Davies G, Downey D, Egan M, Forton J, Gray R, Haworth C, Horsley A, Smyth A, Southern K, Davies J. Future therapies for cystic fibrosis. Nature Communications 2023, 14: 693. PMID: 36755044, PMCID: PMC9907205, DOI: 10.1038/s41467-023-36244-2.Peer-Reviewed Original ResearchConceptsMutation-specific drugsCystic fibrosisSymptom-directed treatmentMultisystem clinical manifestationsCystic fibrosis therapyCystic fibrosis transmembrane conductance regulatorGenetic variantsClinical manifestationsFuture therapiesFibrosis therapyTranslational research collaborationsModulator drugsCFTR modulatorsSingle gene disordersHealth inequalitiesTherapyGene variantsImproved treatmentDrugsPatientsFibrosisFibrosis transmembrane conductance regulatorGene disordersTransmembrane conductance regulatorStrategy group
2022
Non-Modulator Therapies Developing a Therapy for Every Cystic Fibrosis Patient
Egan M. Non-Modulator Therapies Developing a Therapy for Every Cystic Fibrosis Patient. Clinics In Chest Medicine 2022, 43: 717-725. PMID: 36344076, DOI: 10.1016/j.ccm.2022.06.011.Peer-Reviewed Original ResearchConceptsModulator therapyCystic fibrosisCystic fibrosis transmembrane conductance regulator (CFTR) modulator therapiesCFTR modulator therapyTreatment of CFCystic fibrosis patientsGenetic-based therapiesMost patientsCF patientsFibrosis patientsTherapyPremature termination codon mutationsTherapeutic agentsPatientsDNA therapyRNA therapyTermination codon mutationsCodon mutationRecruited 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 targetIn vivo correction of cystic fibrosis mediated by PNA nanoparticles
Piotrowski-Daspit AS, Barone C, Lin CY, Deng Y, Wu D, Binns TC, Xu E, Ricciardi AS, Putman R, Garrison A, Nguyen R, Gupta A, Fan R, Glazer PM, Saltzman WM, Egan ME. In vivo correction of cystic fibrosis mediated by PNA nanoparticles. Science Advances 2022, 8: eabo0522. PMID: 36197984, PMCID: PMC9534507, DOI: 10.1126/sciadv.abo0522.Peer-Reviewed Original ResearchCystic fibrosisF508del miceIntravenous deliveryPrimary nasal epithelial cellsMultiple organ dysfunctionNasal epithelial cellsUssing chamber assaysOrgan dysfunctionF508del cystic fibrosisVivo treatmentGI tissuesCF transmembrane conductance regulator (CFTR) geneChamber assaySystemic deliveryEpithelial cellsCF-causing mutationsFibrosisCFTR functionMiceTransmembrane conductance regulator geneTarget effectsAir-liquid interfaceDeliveryPartial gainViable optionRecruitment 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 cytokinesSurface conjugation of antibodies improves nanoparticle uptake in bronchial epithelial cells
Luks VL, Mandl H, DiRito J, Barone C, Freedman-Weiss MR, Ricciardi AS, Tietjen GG, Egan ME, Saltzman WM, Stitelman DH. Surface conjugation of antibodies improves nanoparticle uptake in bronchial epithelial cells. PLOS ONE 2022, 17: e0266218. PMID: 35385514, PMCID: PMC8986008, DOI: 10.1371/journal.pone.0266218.Peer-Reviewed Original ResearchConceptsTarget-specific antibodiesNanoparticle uptakeSurface conjugationNanoparticle surface modificationSurface of nanoparticlesCellular uptakeSite-specific geneSpecific cellular bindingNanoparticlesIntracellular deliveryEditing reagentsBronchial epithelial cellsSurface modificationCellular targetingCystic fibrosisTherapeutic agentsEpithelial cellsParticle uptakeFeasible strategyGenetic diseasesFirst demonstrationHuman bronchial epithelial cellsKinetics of antibodiesCellular bindingAppropriate antibodies
2021
558: Carbon monoxide–based therapy primes macrophages to express HO-1 and to resolve lung hyper-inflammation in cystic fibrosis
Pietro C, Öz H, Zhang P, Cheng E, Martis V, Bonfield T, Kelley T, Jubin R, Abuchowski A, Krause D, Egan M, Murray T, Bruscia E. 558: Carbon monoxide–based therapy primes macrophages to express HO-1 and to resolve lung hyper-inflammation in cystic fibrosis. Journal Of Cystic Fibrosis 2021, 20: s263-s264. DOI: 10.1016/s1569-1993(21)01981-0.Peer-Reviewed Original Research582: In vivo nanoparticle-mediated therapeutic nucleic acid delivery for CF treatment
Piotrowski-Daspit A, Bracaglia L, Barone C, Nguyen R, Glazer P, Egan M, Saltzman W. 582: In vivo nanoparticle-mediated therapeutic nucleic acid delivery for CF treatment. Journal Of Cystic Fibrosis 2021, 20: s277. DOI: 10.1016/s1569-1993(21)02005-1.Peer-Reviewed Original ResearchUnderstanding the Host in the Management of Pneumonia. An Official American Thoracic Society Workshop Report
Dela Cruz CS, Evans SE, Restrepo MI, Dean N, Torres A, Amara-Elori I, Awasthi S, Caler E, Cao B, Chalmers JD, Chastre J, Cohen TS, Cohen AH, Crothers K, Di YP, Egan ME, Feldman C, Gautam S, Halstead ES, Herold S, Jones BE, Luna C, Niederman MS, Mendez R, Menendez R, Mizgerd JP, Nusrat R, Ramirez J, Shindo Y, Waterer G, Yeligar SM, Wunderink RG. Understanding the Host in the Management of Pneumonia. An Official American Thoracic Society Workshop Report. Annals Of The American Thoracic Society 2021, 18: 1087-1097. PMID: 34242148, PMCID: PMC8328365, DOI: 10.1513/annalsats.202102-209st.BooksConceptsLung infectionOfficial American Thoracic Society Workshop ReportAmerican Thoracic Society meetingLong-term health outcomesRisk of pneumoniaHost risk factorsManagement of pneumoniaExtremes of ageClinical practice guidelinesTreatment of pneumoniaInnovative trial designsPneumonia pathogenesisCritical illnessPulmonary infectionImmunosuppressive disordersPneumonia therapyOutcome definitionsRisk factorsClinical trialsPractice guidelinesRespiratory diseasePneumoniaPneumonia StudySystemic effectsTrial designSPLUNC1: a novel marker of cystic fibrosis exacerbations
Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. SPLUNC1: a novel marker of cystic fibrosis exacerbations. European Respiratory Journal 2021, 58: 2000507. PMID: 33958427, PMCID: PMC8571118, DOI: 10.1183/13993003.00507-2020.Peer-Reviewed Original ResearchConceptsAcute pulmonary exacerbationsSPLUNC1 levelsCystic fibrosisClinical outcomesCF participantsLong-term disease controlNasal epithelium clone 1Cystic fibrosis exacerbationsHigher AE riskLung function declineCytokines interleukin-1βTumor necrosis factorAE riskClinical worseningPulmonary exacerbationsStable patientsLung functionAirway clearanceFunction declineSputum collectionAcute inflammationInflammatory cytokinesMicrobiology findingsCF careClinical managementNanoparticles 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 targetingTherapyEmerging technologies for cystic fibrosis transmembrane conductance regulator restoration in all people with CF
Egan ME. Emerging technologies for cystic fibrosis transmembrane conductance regulator restoration in all people with CF. Pediatric Pulmonology 2021, 56: s32-s39. PMID: 32681713, PMCID: PMC8114183, DOI: 10.1002/ppul.24965.Peer-Reviewed Original Research
2020
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytesCystic fibrosis transmembrane conductance receptor modulator therapy in cystic fibrosis, an update.
Egan ME. Cystic fibrosis transmembrane conductance receptor modulator therapy in cystic fibrosis, an update. Current Opinion In Pediatrics 2020, 32: 384-388. PMID: 32374578, DOI: 10.1097/mop.0000000000000892.Peer-Reviewed Original ResearchConceptsModulator therapyCystic fibrosisCFTR modulatorsLung functionElexacaftor/tezacaftor/ivacaftorEffective CFTR modulatorsEffective triple therapyTezacaftor/ivacaftorMonths of ageQuality of lifeCystic fibrosis patientsLong-term usePulmonary exacerbationsTriple therapyFirst therapyLong-term benefitsReceptor modulatorsFibrosisFibrosis patientsTherapyUnderlying causeWeight gainPatientsImproved healthCFTR mutations