2024
CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and Cystic Fibrosis mice
Öz H, Braga C, Gudneppanavar R, Di Pietro C, Huang P, Zhang P, Krause D, Egan M, Murray T, Bruscia E. CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and Cystic Fibrosis mice. Journal Of Leukocyte Biology 2024, qiae218. PMID: 39365279, DOI: 10.1093/jleuko/qiae218.Peer-Reviewed Original ResearchLung tissue damageCystic fibrosisTissue damageMonocyte recruitmentImmune responsePulmonary Pseudomonas aeruginosa infectionHyper-inflammatory immune responseCystic fibrosis micePropagate tissue damagePseudomonas aeruginosaLungs of patientsChronic neutrophilic inflammationImmunological response to infectionHost immune responseMonocyte-derived macrophagesTarget monocyte recruitmentSite of injuryResponse to infectionCFTR modulatorsPA infectionChronic inflammatory disease conditionsReduced bactericidal activityAdjunctive therapyClinical outcomesEradicate infection285 Development of an electrochemiluminescence CFTR immunoassay
Browne J, Lee J, Peterec K, Garrison A, Bruscia E, Saltzman W, Egan M. 285 Development of an electrochemiluminescence CFTR immunoassay. Journal Of Cystic Fibrosis 2024, 23: s152. DOI: 10.1016/s1569-1993(24)01125-1.Peer-Reviewed Original Research264 Poly(amine-co-ester) nanoparticle delivery of CFTR mRNA shows restoration of CFTR activity in cystic fibrosis airway models
Garrison A, Lee J, Browne J, Akhtar L, Peterec K, Suberi A, Eaton D, Ene M, Zhang X, Whang C, Oez H, Kizilirmak T, Bruscia E, Piotrowski-Daspit A, Saltzman W, Egan M. 264 Poly(amine-co-ester) nanoparticle delivery of CFTR mRNA shows restoration of CFTR activity in cystic fibrosis airway models. Journal Of Cystic Fibrosis 2024, 23: s140-s141. DOI: 10.1016/s1569-1993(24)01104-4.Peer-Reviewed Original Research395 Altered hematopoiesis and functional decline of hematopoietic stem cells in cystic fibrosis mice
Braga C, Mancuso R, Thompson E, Oez H, Gudneppannavar R, Zhang P, Huang P, Egan M, Murray T, Krause D, Bruscia E. 395 Altered hematopoiesis and functional decline of hematopoietic stem cells in cystic fibrosis mice. Journal Of Cystic Fibrosis 2024, 23: s207-s208. DOI: 10.1016/s1569-1993(24)01235-9.Peer-Reviewed Original Research256 Primary mouse tracheal basal cells transplanted into CFTR−/− mice reconstitute CFTR function
Chen K, Berical A, Oez H, Braga C, Garrison A, Gudneppanavar R, Egan M, Kotton D, Bruscia E, Hawkins F. 256 Primary mouse tracheal basal cells transplanted into CFTR−/− mice reconstitute CFTR function. Journal Of Cystic Fibrosis 2024, 23: s136. DOI: 10.1016/s1569-1993(24)01096-8.Peer-Reviewed Original Research219 CFTR dysfunction shapes airway immune cell compositions contributing to lung pathogenesis in children with cystic fibrosis
Kizilirmak T, Yin H, Garrison A, Browne J, Bruscia E, Egan M, Britto C. 219 CFTR dysfunction shapes airway immune cell compositions contributing to lung pathogenesis in children with cystic fibrosis. Journal Of Cystic Fibrosis 2024, 23: s119. DOI: 10.1016/s1569-1993(24)01059-2.Peer-Reviewed Original ResearchUnderstanding 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 ResearchPrior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters
Di Pietro C, Haberman A, Lindenbach B, Smith P, Bruscia E, Allore H, Vander Wyk B, Tyagi A, Zeiss C. Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters. Viruses 2024, 16: 246. PMID: 38400021, PMCID: PMC10891789, DOI: 10.3390/v16020246.Peer-Reviewed Original ResearchConceptsTransient gene expressionSARS-CoV-2Viral replication pathwayReplication pathwayAntiviral pathwaysEndemism patternsUpregulation of innateGene expressionQuantitative RT-PCRMitigated weight lossDual-infected animalsSARS-CoV-2 viral loadSARS-CoV-2 infectionSyrian hamstersSeasonal infection ratesSARS-CoV-2 inoculationLungs of animalsIndividual virusesSARS-CoV-2 diseaseUpper respiratory tractH1N1 infectionRT-PCRBronchoalveolar lavageViral loadCytokine levelsDe-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 ResearchThe effects of elexafactor/tezafactor/ivacaftor beyond the epithelium: spurring macrophages to fight infections.
Bruscia E. The effects of elexafactor/tezafactor/ivacaftor beyond the epithelium: spurring macrophages to fight infections. European Respiratory Journal 2023, 61: 2300216. PMID: 37003613, DOI: 10.1183/13993003.00216-2023.Peer-Reviewed Original Research
2022
Update on Innate and Adaptive Immunity in Cystic Fibrosis
Bruscia E, Bonfield T. Update on Innate and Adaptive Immunity in Cystic Fibrosis. Clinics In Chest Medicine 2022, 43: 603-615. PMID: 36344069, DOI: 10.1016/j.ccm.2022.06.004.Peer-Reviewed Original ResearchConceptsChronic infectionCFTR modulator therapyRobust inflammatory responseCystic fibrosis pathophysiologyImmune dysregulationPatient ageExcessive inflammationModulator therapyLung microenvironmentLung infectionImmune mechanismsInflammatory responseAdaptive immunityMucociliary transportCF life expectancyCF lungCystic fibrosisInfectionLife expectancyImmunityCritical roleCurrent understandingMorbidityInflammationFibrosisRecruited 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 targetHuman neutrophil development and functionality are enabled in a humanized mouse model
Zheng Y, Sefik E, Astle J, Karatepe K, Öz HH, Solis AG, Jackson R, Luo HR, Bruscia EM, Halene S, Shan L, Flavell RA. Human neutrophil development and functionality are enabled in a humanized mouse model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2121077119. PMID: 36269862, PMCID: PMC9618085, DOI: 10.1073/pnas.2121077119.Peer-Reviewed Original ResearchConceptsHumanized mouse modelMouse modelHuman immune systemHuman neutrophilsImmune systemFunctional human immune systemGranulocyte colony-stimulating factorUnique mouse modelColony-stimulating factorHuman G-CSFMISTRG miceG-CSF receptor geneBacterial burdenInfectious challengeG-CSFNeutrophilsMiceNeutrophil developmentReceptor geneDiseaseEmerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis
Jaganathan D, Bruscia EM, Kopp BT. Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis. International Journal Of Molecular Sciences 2022, 23: 7750. PMID: 35887098, PMCID: PMC9319215, DOI: 10.3390/ijms23147750.Peer-Reviewed Original ResearchConceptsPhagosome formationCystic fibrosis transmembrane conductance regulator (CFTR) geneTransmembrane conductance regulator geneInnate immunityTissue homeostasisRegulator geneMutant CFTRCF macrophagesCystic fibrosisPhagocytic mechanismsPathogenic microbesAdaptive immune systemDefective macrophage phagocytosisCFTRCurrent understandingTherapeutic developmentCentral roleMacrophage phagocytosisCFTR modulatorsPhagocytic cellsPhagocytosisNew therapeutic developmentsMacrophages contributesLung functionChronic inflammationGene therapy applications to transfusion medicine
Tabibi S, Gehrie E, Bruscia E, Krause D. Gene therapy applications to transfusion medicine. 2022, 642-647. DOI: 10.1002/9781119719809.ch56.ChaptersGene therapyVector-based gene therapyViral vector-based gene therapyGene therapy applicationsTranscription activator-like effector nucleasesZinc finger nucleasesGene-editing approachesNonviral vectorsGene-editing techniquesGene integrationTherapy applicationsFinger nucleasesEffector nucleasesViral vectorsReplication-competent virusPossible applicationsGenetic materialApplicationsNucleaseTarget cellsVectorCRISPRRecruitment 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
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 ResearchCombined liver–cytokine humanization comes to the rescue of circulating human red blood cells
Song Y, Shan L, Gbyli R, Liu W, Strowig T, Patel A, Fu X, Wang X, Xu ML, Gao Y, Qin A, Bruscia EM, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Eynon E, Gonzalez DG, Chen J, Krause DS, Alderman J, Halene S, Flavell RA. Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells. Science 2021, 371: 1019-1025. PMID: 33674488, PMCID: PMC8292008, DOI: 10.1126/science.abe2485.Peer-Reviewed Original ResearchConceptsRed blood cellsBlood cellsHuman sickle cell diseaseSickle cell diseaseImmunodeficient murine modelKupffer cell densityBone marrow failureMISTRG miceIntrasplenic injectionSCD pathologyCell diseaseMurine modelComplement C3RBC survivalVivo modelHuman cytokinesPreclinical testingHematopoietic stem cellsHuman red blood cellsMarrow failureFumarylacetoacetate hydrolase geneHuman erythropoiesisHuman liverHuman hepatocytesMice
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 phagocytes