2024
Prior 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 levels
2023
The 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
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 targetUpdate 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 understandingMorbidityInflammationFibrosisHuman 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 inflammation
2021
Combined 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
2019
A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies
Song Y, Rongvaux A, Taylor A, Jiang T, Tebaldi T, Balasubramanian K, Bagale A, Terzi YK, Gbyli R, Wang X, Fu X, Gao Y, Zhao J, Podoltsev N, Xu M, Neparidze N, Wong E, Torres R, Bruscia EM, Kluger Y, Manz MG, Flavell RA, Halene S. A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies. Nature Communications 2019, 10: 366. PMID: 30664659, PMCID: PMC6341122, DOI: 10.1038/s41467-018-08166-x.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsMyelodysplastic syndromeXenotransplantation modelDysplastic morphologyImmunodeficient murine hostsPre-clinical studiesMDS stem cellsMDS subtypesComprehensive preclinical studiesPreclinical studiesTherapeutic efficacyMurine hostSerial transplantationDrug mechanismsMDS researchStem cell propagationStem cellsDifferentiation potentialHematopoietic stem cell nicheGenetic complexityNovel avenuesStem cell nicheCell propagationDisease representationsImmunodeficient
2016
Cellular Innate Immunity: An Old Game with New Players
Gasteiger G, D'Osualdo A, Schubert DA, Weber A, Bruscia EM, Hartl D. Cellular Innate Immunity: An Old Game with New Players. Journal Of Innate Immunity 2016, 9: 111-125. PMID: 28006777, PMCID: PMC6738785, DOI: 10.1159/000453397.Peer-Reviewed Original ResearchConceptsInnate immunityMyeloid-derived suppressor cellsInnate lymphoid cellsInnate immune cellsAdaptive immune responsesNovel therapeutic opportunitiesCell typesSuppressor cellsImmune cellsImmune responseLymphoid cellsTherapeutic opportunitiesInfectious diseasesCurrent conceptsMolecular pathwaysImmunityCellsNovel cell typesInflammasomeDiseaseCystic Fibrosis Lung Immunity: The Role of the Macrophage
Bruscia EM, Bonfield TL. Cystic Fibrosis Lung Immunity: The Role of the Macrophage. Journal Of Innate Immunity 2016, 8: 550-563. PMID: 27336915, PMCID: PMC5089923, DOI: 10.1159/000446825.Peer-Reviewed Original ResearchConceptsLung homeostasisCystic fibrosis pathophysiologyTranscriptional shiftMortality of patientsEnvironmental cuesAdaptive immune networkModifier genesMΦ functionMajor morbidityExcessive inflammationMΦ phenotypeLung infectionCF lungCFTR dysfunctionMajor playersHomeostasisDiseaseMacrophagesIntrinsic changesGenesImmune networkPhenotypeMorbidityInflammationPatients
2015
Innate and Adaptive Immunity in Cystic Fibrosis
Bruscia EM, Bonfield TL. Innate and Adaptive Immunity in Cystic Fibrosis. Clinics In Chest Medicine 2015, 37: 17-29. PMID: 26857765, DOI: 10.1016/j.ccm.2015.11.010.Peer-Reviewed Original ResearchConceptsImmune cellsCystic fibrosis lung diseaseLung tissue destructionAnti-inflammatory cytokinesRobust inflammatory responseElevated proinflammatoryImmune dysregulationUnresolved inflammationLung diseaseInflammatory responseLeading causeCF patientsTissue destructionAdaptive immunityCF lungCystic fibrosisHost defenseElevated numbersExocrine pancreasHyperinflammationLungTissue integrityCurrent understandingCellsProinflammatoryPharmacological 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
Disease-relevant proteostasis regulation of cystic fibrosis transmembrane conductance regulator
Villella VR, Esposito S, Bruscia EM, Vicinanza M, Cenci S, Guido S, Pettoello-Mantovani M, Carnuccio R, De Matteis MA, Luini A, Maiuri MC, Raia V, Kroemer G, Maiuri L. Disease-relevant proteostasis regulation of cystic fibrosis transmembrane conductance regulator. Cell Death & Differentiation 2013, 20: 1101-1115. PMID: 23686137, PMCID: PMC3705602, DOI: 10.1038/cdd.2013.46.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsBeclin-1BronchiCell LineCell MembraneCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsHumansMembrane ProteinsMutationPhosphoric Monoester HydrolasesProteostasis DeficienciesRab5 GTP-Binding ProteinsReceptors, TransferrinSequestosome-1 ProteinConceptsCFTR proteinBronchial epithelial cellsCFTR surface expressionSmall GTPase Rab5Cystic fibrosis transmembrane conductance regulatorFibrosis transmembrane conductance regulatorWild-type CFTRFunctional CFTR proteinSQSTM1/p62Transmembrane conductance regulatorPositive feed-forward loopPlasma membrane stabilityFeed-forward loopEpithelial cellsProteostasis regulationProtein traffickingProteostasis networkGTPase Rab5Rab5 effectorProteostasis regulatorsConformational diseasesCystic fibrosis transmembrane conductance regulator (CFTR) potentiatorRecycling defectsSQSTM1 accumulationUnexpected linkReduced 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
2012
Innate immunity in cystic fibrosis lung disease
Hartl D, Gaggar A, Bruscia E, Hector A, Marcos V, Jung A, Greene C, McElvaney G, Mall M, Döring G. Innate immunity in cystic fibrosis lung disease. Journal Of Cystic Fibrosis 2012, 11: 363-382. PMID: 22917571, DOI: 10.1016/j.jcf.2012.07.003.Peer-Reviewed Original ResearchConceptsLung diseaseCF lung diseaseInnate immunityChronic infective lung diseaseNovel immune-targeted therapiesCystic fibrosis lung diseasePulmonary immune responseChronic lung diseaseImmune-targeted therapiesPro-inflammatory cascadeInfective lung diseaseInnate immune regulationInnate immune systemCystic fibrosis patientsPotential clinical relevanceEpithelial dysfunctionLeukocyte recruitmentImmune regulationImmune responseAdaptive immunityClinical relevanceFibrosis patientsImmune systemDiseaseImmunityNebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice
Gavina M, Luciani A, Villella VR, Esposito S, Ferrari E, Bressani I, Casale A, Bruscia EM, Maiuri L, Raia V. Nebulized Hyaluronan Ameliorates lung inflammation in cystic fibrosis mice. Pediatric Pulmonology 2012, 48: 761-771. PMID: 22825912, DOI: 10.1002/ppul.22637.Peer-Reviewed Original ResearchConceptsLung inflammationCystic fibrosisLung tissueReactive oxygen speciesScnn1b-Tg miceHuman airway epithelial cellsSaline-treated miceChronic lung inflammationInflammatory protein-2Chronic respiratory diseasesPeroxisome Proliferator-Activated Receptor GammaPotential anti-inflammatory drugsAnti-inflammatory drugsAirway epithelial cellsCystic fibrosis miceIB3-1Myeloperoxidase levelsMIP-2MPO activityMacrophage infiltrationFibrosis miceTumor necrosisExogenous administrationTNFα expressionCF airwaysThe Carbon Monoxide Releasing Molecule CORM-2 Attenuates Pseudomonas aeruginosa Biofilm Formation
Murray TS, Okegbe C, Gao Y, Kazmierczak BI, Motterlini R, Dietrich LE, Bruscia EM. The Carbon Monoxide Releasing Molecule CORM-2 Attenuates Pseudomonas aeruginosa Biofilm Formation. PLOS ONE 2012, 7: e35499. PMID: 22563385, PMCID: PMC3338523, DOI: 10.1371/journal.pone.0035499.Peer-Reviewed Original ResearchConceptsCORM-2 treatmentP. aeruginosa lung infectionP. aeruginosaAeruginosa lung infectionCORM-2Clinical P. aeruginosaMolecule CORM-2Current antimicrobial agentsChronic infectionLung infectionNew therapiesRelated infectionsNon-mucoid strainsReactive oxygen speciesInfectionNovel therapeutic propertiesTherapeutic propertiesAntimicrobial agentsAdditive effectPseudomonas aeruginosaBiofilm formationOxygen speciesTreatmentAeruginosa
2011
Abnormal 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
Role for MKL1 in megakaryocytic maturation
Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, Tuck D, Schulz V, Mane SM, Berliner N, Sun Y, Morris SW, Qiu C, Krause DS. Role for MKL1 in megakaryocytic maturation. Blood 2009, 113: 2826-2834. PMID: 19136660, PMCID: PMC2661865, DOI: 10.1182/blood-2008-09-180596.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood Cell CountBone MarrowCell DifferentiationCell Line, TumorCells, CulturedDNA-Binding ProteinsGene Expression ProfilingGene Expression RegulationHumansLeukemia, Erythroblastic, AcuteMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisOncogene Proteins, FusionPloidiesRecombinant Fusion ProteinsRNA InterferenceRNA, Small InterferingSerum Response FactorThrombocytopeniaThrombopoiesisThrombopoietinTrans-ActivatorsConceptsMegakaryoblastic leukemia 1Reduced platelet countsSerum response factorMegakaryocytic differentiationPeripheral bloodPlatelet countMKL1 expressionMegakaryoblastic leukemiaBone marrow megakaryocytesMuscle cellsPresence of thrombopoietinPhysiologic maturationHuman erythroleukemia cell lineIncreased numberMarrow megakaryocytesCell linesErythroleukemia cell lineMegakaryocytesMegakaryocytic maturationDifferentiated muscle cellsOverexpressionConcurrent increaseMuscle differentiationCellsMaturation