2023
Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination
Suberi A, Grun M, Mao T, Israelow B, Reschke M, Grundler J, Akhtar L, Lee T, Shin K, Piotrowski-Daspit A, Homer R, Iwasaki A, Suh H, Saltzman W. Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination. Science Translational Medicine 2023, 15: eabq0603. PMID: 37585505, PMCID: PMC11137749, DOI: 10.1126/scitranslmed.abq0603.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Lethal viral challengeAntigen-presenting cellsSyndrome coronavirus 2Humoral adaptive immunityLung-targeting deliveryIntranasal vaccinationMucosal vaccinationPulmonary diseaseMucosal vaccinesSusceptible miceCoronavirus 2Viral challengeAdaptive immunityLungTranslational potentialMessenger RNA (mRNA) therapeuticsVaccinationMRNADeliveryTherapeuticsRNA therapeuticsTherapeutic delivery
2020
Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis
Adams TS, Schupp JC, Poli S, Ayaub EA, Neumark N, Ahangari F, Chu SG, Raby BA, DeIuliis G, Januszyk M, Duan Q, Arnett HA, Siddiqui A, Washko GR, Homer R, Yan X, Rosas IO, Kaminski N. Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis. Science Advances 2020, 6: eaba1983. PMID: 32832599, PMCID: PMC7439502, DOI: 10.1126/sciadv.aba1983.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisVascular endothelial cellsIPF lungsPulmonary fibrosisChronic obstructive pulmonary disease (COPD) lungsFatal interstitial lung diseaseEndothelial cellsInterstitial lung diseaseCell populationsIPF myofibroblastsMyofibroblast fociNonsmoker controlsLung diseaseCOPD lungsBasaloid cellsSingle-cell atlasInvasive fibroblastsMacrophage populationsLungStromal cellsEpithelial cellsFibrosisCellular populationsDevelopmental markersSingle-cell RNA-seq
2019
Transcriptional regulatory model of fibrosis progression in the human lung
McDonough JE, Ahangari F, Li Q, Jain S, Verleden SE, Herazo-Maya J, Vukmirovic M, DeIuliis G, Tzouvelekis A, Tanabe N, Chu F, Yan X, Verschakelen J, Homer RJ, Manatakis DV, Zhang J, Ding J, Maes K, De Sadeleer L, Vos R, Neyrinck A, Benos PV, Bar-Joseph Z, Tantin D, Hogg JC, Vanaudenaerde BM, Wuyts WA, Kaminski N. Transcriptional regulatory model of fibrosis progression in the human lung. JCI Insight 2019, 4 PMID: 31600171, PMCID: PMC6948862, DOI: 10.1172/jci.insight.131597.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAdvanced fibrosisAlveolar surface densityFibrosis progressionLung fibrosisHuman lungDynamic Regulatory Events MinerExtent of fibrosisIPF lungsPulmonary fibrosisControl lungsIPF tissueB lymphocytesFibrosisLungLinear mixed-effects modelsMixed-effects modelsGene expression changesSystems biology modelsDifferential gene expression analysisGene expression analysisProgressionGene expression networksRNA sequencingBiology models
2016
Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis
Peng X, Moore M, Mathur A, Zhou Y, Sun H, Gan Y, Herazo‐Maya J, Kaminski N, Hu X, Pan H, Ryu C, Osafo‐Addo A, Homer RJ, Feghali‐Bostwick C, Fares W, Gulati M, Hu B, Lee C, Elias JA, Herzog EL. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis. The FASEB Journal 2016, 30: 4056-4070. PMID: 27609773, PMCID: PMC5102121, DOI: 10.1096/fj.201600373r.Peer-Reviewed Original ResearchConceptsLung fibrosisPlexin C1Macrophage migrationPulmonary fibrosisBone marrow-derived cellsSynaptotagmin-7Idiopathic pulmonary fibrosisInterstitial lung diseaseMarrow-derived cellsTGF-β1 overexpressionFatal conditionLung diseaseMonocyte migrationUnrecognized observationCollagen accumulationFibrosisMice showBoyden chamberGenetic deletionLungMouse macrophagesSemaphorin receptorsMacrophagesC1s deficiencyDeficiency
2014
Introductory Anatomy, Histology, and Cell Biology of the Lung
Homer R, Britto C. Introductory Anatomy, Histology, and Cell Biology of the Lung. 2014, 2538-2557. DOI: 10.1016/b978-0-12-386456-7.05301-6.Peer-Reviewed Original ResearchMajor anatomical componentsGas exchange regionSmooth muscleSystemic circulationBlood flowConducting airwaysGas exchange unitsHematopoietic elementsHost defenseAirwayProtective mechanismLungParallel conduction pathwaysEnvironmental exposuresHarmful agentsBloodExchange regionAnatomical componentsTissueNerveHistologyReflexInterstitiumAlveoliVasculature
2013
Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway
Choo-Wing R, Syed MA, Harijith A, Bowen B, Pryhuber G, Janér C, Andersson S, Homer RJ, Bhandari V. Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway. American Journal Of Respiratory Cell And Molecular Biology 2013, 48: 749-757. PMID: 23470621, PMCID: PMC3727872, DOI: 10.1165/rcmb.2012-0381oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBronchopulmonary DysplasiaCelecoxibCell DeathCyclooxygenase 2Cyclooxygenase 2 InhibitorsEndoplasmic Reticulum StressHumansHyperoxiaImmunohistochemistryInfant, NewbornInterferon-gammaLungMiceMice, Inbred C57BLMice, TransgenicPyrazolesRNA, Small InterferingSulfonamidesTranscription Factor CHOPConceptsBronchopulmonary dysplasiaCyclooxygenase-2Endoplasmic reticulum stress-dependent pathwaysER stress pathway activationPathway mediatorsHuman bronchopulmonary dysplasiaFinal common pathwayAlveolar epithelial cellsImpaired alveolarizationStress pathway activationCOX2 inhibitionMurine modelMurine lungClinical relevanceIFNVivo modelHyperoxiaLungHuman lungPathway activationCHOP siRNAStress-dependent pathwaysInjuryEpithelial cellsCommon pathway
2011
Modern concepts on the role of inflammation in pulmonary fibrosis.
Homer RJ, Elias JA, Lee CG, Herzog E. Modern concepts on the role of inflammation in pulmonary fibrosis. Archives Of Pathology & Laboratory Medicine 2011, 135: 780-8. PMID: 21631273, DOI: 10.5858/2010-0296-ra.1.BooksConceptsRole of inflammationIdiopathic pulmonary fibrosisPulmonary fibrosisTherapeutic interventionsResult of inflammationCell deathLung transplantationCytokine environmentMacrophage polarizationInflammationFibrosisLethal diseaseLimited biomarkersClinical contextDisease biomarkersBiomarkersDeathInterventionUnpublished researchTransplantationLungDiseaseA Role for Matrix Metalloproteinase 9 in IFNγ-Mediated Injury in Developing Lungs
Harijith A, Choo-Wing R, Cataltepe S, Yasumatsu R, Aghai ZH, Janér J, Andersson S, Homer RJ, Bhandari V. A Role for Matrix Metalloproteinase 9 in IFNγ-Mediated Injury in Developing Lungs. American Journal Of Respiratory Cell And Molecular Biology 2011, 44: 621-630. PMID: 21216975, PMCID: PMC3095982, DOI: 10.1165/rcmb.2010-0058oc.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaHuman bronchopulmonary dysplasiaLung architectureRole of IFNγMatrix metalloproteinase-9Caspase-3Final common pathwayMatrix metalloproteinases 2Downstream targetsImpaired alveolarizationLung injuryChemokine ligandMetalloproteinase-9IFNγ mRNAAngiopoietin-2Murine modelLittermate controlsPulmonary phenotypeMurine lungClinical relevanceLung phenotypeAngiopoietin-1IFNγMetalloproteinases 2Lung
2010
Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation
Wright PL, Yu J, Di YP, Homer RJ, Chupp G, Elias JA, Cohn L, Sessa WC. Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation. Journal Of Experimental Medicine 2010, 207: 2595-2607. PMID: 20975041, PMCID: PMC2989775, DOI: 10.1084/jem.20100786.Peer-Reviewed Original ResearchConceptsLung inflammationTh2-mediated lung inflammationSevere human asthmaAsthma-like phenotypeNonallergic miceHuman asthmaInflammation resultsKO miceLung tissueNogo expressionAirway epitheliumSmooth muscleReticulon 4BTransgenic miceLung epitheliumEpithelial reconstitutionMiceMarked reductionProtective genesEndogenous regulatorNogoInflammationLungPLUNCTransgenic expression
2008
Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung
Bhandari V, Choo-Wing R, Lee CG, Yusuf K, Nedrelow JH, Ambalavanan N, Malkus H, Homer RJ, Elias JA. Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung. American Journal Of Respiratory Cell And Molecular Biology 2008, 39: 420-430. PMID: 18441284, PMCID: PMC2551703, DOI: 10.1165/rcmb.2007-0024oc.Peer-Reviewed Original ResearchMeSH KeywordsAmniotic FluidAnimalsAnimals, NewbornBronchopulmonary DysplasiaCapillary PermeabilityFemaleHemorrhageHumansHyperoxiaInfant, NewbornLungLung DiseasesMiceMice, TransgenicNitric OxidePregnancyPulmonary SurfactantsRespiratory Distress Syndrome, NewbornTracheaVascular Endothelial Growth Factor AConceptsVascular endothelial growth factorVEGF levelsLung developmentNitric oxide mediationNO-dependent mechanismAdult murine lungPotential clinical benefitTransgenic murine modelSignificant differencesEndothelial growth factorBronchopulmonary dysplasiaLung injuryPulmonary hemorrhageCytokine responsesClinical benefitNeonatal lungHuman neonatesMurine modelMurine lungMature lungLungPathologic conditionsAdult lungSurfactant phospholipidsExtravascular effects
2006
IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells
Temann UA, Laouar Y, Eynon EE, Homer R, Flavell RA. IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells. International Immunology 2006, 19: 1-10. PMID: 17101709, DOI: 10.1093/intimm/dxl117.Peer-Reviewed Original ResearchConceptsAirway epithelial cellsLung inflammationTg miceEnhanced lung inflammationEosinophilic lung inflammationEpithelial cellsMast cell hyperplasiaAsthma-like phenotypeRecombinase-activating genes 1IL13 levelsMucus hypersecretionCell hyperplasiaInflammatory cytokinesLung pathologyLung sectionsT cellsMast cellsMucus productionIL13 expressionB cellsLung epitheliumTransgenic miceInflammationIL13LungEssential role of nitric oxide in VEGF-induced, asthma-like angiogenic, inflammatory, mucus, and physiologic responses in the lung
Bhandari V, Choo-Wing R, Chapoval SP, Lee CG, Tang C, Kim YK, Ma B, Baluk P, Lin MI, McDonald DM, Homer RJ, Sessa WC, Elias JA. Essential role of nitric oxide in VEGF-induced, asthma-like angiogenic, inflammatory, mucus, and physiologic responses in the lung. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 11021-11026. PMID: 16832062, PMCID: PMC1544167, DOI: 10.1073/pnas.0601057103.Peer-Reviewed Original ResearchConceptsInducible NOSNitric oxideEndothelial NOS inhibitorDendritic cell activationNO-dependent mechanismAirway hyperresponsivenessMucus metaplasiaLymphocyte accumulationPulmonary alterationsCell hyperplasiaNOS inhibitorNormal micePhysiologic responsesCell activationInflammationENOSVEGFMiceIndependent mechanismsTissue responseLatter responseLungAngiogenesisRemodelingNull mutation
2005
ERK1/2 mitogen-activated protein kinase selectively mediates IL-13–induced lung inflammation and remodeling in vivo
Lee PJ, Zhang X, Shan P, Ma B, Lee CG, Homer RJ, Zhu Z, Rincon M, Mossman BT, Elias JA. ERK1/2 mitogen-activated protein kinase selectively mediates IL-13–induced lung inflammation and remodeling in vivo. Journal Of Clinical Investigation 2005, 116: 163-173. PMID: 16374521, PMCID: PMC1319220, DOI: 10.1172/jci25711.Peer-Reviewed Original ResearchConceptsIL-13-induced inflammationIL-13IL-13 expressionSTAT6-independent mannerIL-13 stimulationLung inflammationSpecific chemokinesTg miceEffector responsesSystemic administrationMMP-2Alveolar remodelingInflammationLungCritical rolePotent activationTissue effectsERK1/2 activationSTAT6ChemokinesInhibitor PD98059ERK1/2ERK1/2 mitogenRemodelingDisease
2004
Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung
Lee CG, Link H, Baluk P, Homer RJ, Chapoval S, Bhandari V, Kang MJ, Cohn L, Kim YK, McDonald DM, Elias JA. Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nature Medicine 2004, 10: 1095-1103. PMID: 15378055, PMCID: PMC3434232, DOI: 10.1038/nm1105.Peer-Reviewed Original ResearchConceptsTh2 inflammationAntigen sensitizationT helper type 2 cellsAntigen-induced inflammationAsthma-like phenotypeType 2 cellsRole of VEGFMucus metaplasiaDendritic cellsAsthmatic lungCytokine productionTh1 cellsVascular remodelingInflammationTransgenic micePhysiologic dysregulationMyocyte hyperplasiaExaggerated levelsVEGFEpithelial cellsSensitizationAsthmaTh2VEGF regulationLungEarly Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis
Lee CG, Cho SJ, Kang MJ, Chapoval SP, Lee PJ, Noble PW, Yehualaeshet T, Lu B, Flavell RA, Milbrandt J, Homer RJ, Elias JA. Early Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis. Journal Of Experimental Medicine 2004, 200: 377-389. PMID: 15289506, PMCID: PMC2211975, DOI: 10.1084/jem.20040104.Peer-Reviewed Original ResearchConceptsVivo effector functionGrowth factor-β1Early growth response gene-1Pulmonary fibrosisSeptal rupturePulmonary disordersInterstitial diseaseEffector functionsFibrotic responseMurine lungTissue fibrosisEpithelial apoptosisFactor-β1Alveolar remodelingResponse gene-1FibrosisBioactive TGFTGFMyocyte hyperplasiaGrowth factorEarly growth response geneApoptosisLungPathogenesisGene 1Activation of the STAT pathway in acute lung injury
Severgnini M, Takahashi S, Rozo LM, Homer RJ, Kuhn C, Jhung JW, Perides G, Steer M, Hassoun PM, Fanburg BL, Cochran BH, Simon AR. Activation of the STAT pathway in acute lung injury. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2004, 286: l1282-l1292. PMID: 14729509, DOI: 10.1152/ajplung.00349.2003.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsCells, CulturedDisease Models, AnimalDNA-Binding ProteinsHydrochloric AcidInterleukin-6Janus Kinase 2KineticsLipopolysaccharidesLiverLungMaleMiceMice, Inbred BALB CMice, Inbred C57BLMitogen-Activated Protein KinasesOxidation-ReductionPancreatitisProtein-Tyrosine KinasesProto-Oncogene ProteinsRespiratory Distress SyndromeRespiratory MucosaSrc-Family KinasesSTAT3 Transcription FactorTrans-ActivatorsTumor Necrosis Factor-alphaConceptsAcute lung injuryIL-6Lung injuryLPS treatmentDevastating clinical problemGastric acid aspirationIntranasal LPS administrationResident lung cellsSTAT3 activationAcute pancreatitis modelSTAT activationAcid aspirationLPS administrationCytokine responsesInflammatory cellsInflammatory responsePancreatitis modelClinical problemMultiple organsLungLung cellsLPSEndothelial cellsTranscription factorsCritical mediator
2003
Transgenic Modeling of Interleukin-13 in the Lung
Elias JA, Zheng T, Lee CG, Homer RJ, Chen Q, Ma B, Blackburn M, Zhu Z. Transgenic Modeling of Interleukin-13 in the Lung. CHEST Journal 2003, 123: 339s-345s. PMID: 12628968, DOI: 10.1378/chest.123.3_suppl.339s.Peer-Reviewed Original ResearchConceptsChemokine receptor 2Vascular endothelial growth factorIL-13 inducesRegulation of inflammationGrowth factor-β1Endothelial growth factorOverexpression transgenic miceAsthma pathogenesisMurine airwaysKey cytokineInterleukin-13Receptor 2Factor-β1Transgenic miceIL-11Transgenic modelingLungGrowth factorPhenotypic alterationsGenetic targetsAirwayInflammationInterleukinStudy resultsCytokines
2000
Interferon γ Induction of Pulmonary Emphysema in the Adult Murine Lung
Wang Z, Zheng T, Zhu Z, Homer R, Riese R, Chapman H, Shapiro S, Elias J. Interferon γ Induction of Pulmonary Emphysema in the Adult Murine Lung. Journal Of Experimental Medicine 2000, 192: 1587-1600. PMID: 11104801, PMCID: PMC2193095, DOI: 10.1084/jem.192.11.1587.Peer-Reviewed Original ResearchConceptsAdult murine lungMurine lungProtease/antiprotease balanceChronic obstructive pulmonary diseaseSecretory leukocyte proteinase inhibitorNeutrophil-rich inflammationObstructive pulmonary diseaseInterferon γ inductionPulmonary diseasePulmonary complianceChronic inflammationInflammatory responseLung volumePulmonary emphysemaPulmonary tissueΓ inductionAlveolar enlargementMMP-9Matrix metalloproteinaseEmphysemaLungInflammationSelective inhibitionProminent proteaseMacrophagesInducible targeting of IL-13 to the adult lung causes matrix metalloproteinase– and cathepsin-dependent emphysema
Zheng T, Zhu Z, Wang Z, Homer R, Ma B, Riese R, Chapman H, Shapiro S, Elias J. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase– and cathepsin-dependent emphysema. Journal Of Clinical Investigation 2000, 106: 1081-1093. PMID: 11067861, PMCID: PMC301418, DOI: 10.1172/jci10458.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseCigarette smoke exposureIL-13Smoke exposureSignificant chronic obstructive pulmonary diseaseObstructive pulmonary diseaseAdult murine lungMinority of smokersVaried natural historyAirway hyperresponsivenessMucus metaplasiaLung functionPulmonary diseasePulmonary inflammationLung volumeCritical cytokineMurine lungMMP-2Matrix metalloproteinaseInflammationPotent stimulatorEmphysemaAdult lungLungNatural historyMorphometry Explains Variation in Airway Responsiveness in Transgenic Mice Overexpressing Interleukin-6 and Interleukin-11 in the Lung
Kuhn C, Homer R, Zhu Z, Ward N, Elias J. Morphometry Explains Variation in Airway Responsiveness in Transgenic Mice Overexpressing Interleukin-6 and Interleukin-11 in the Lung. CHEST Journal 2000, 117: 260s-262s. PMID: 10843940, DOI: 10.1016/s0012-3692(15)51023-4.Peer-Reviewed Original Research