2023
SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis
Barbayianni I, Kanellopoulou P, Fanidis D, Nastos D, Ntouskou E, Galaris A, Harokopos V, Hatzis P, Tsitoura E, Homer R, Kaminski N, Antoniou K, Crestani B, Tzouvelekis A, Aidinis V. SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis. Nature Communications 2023, 14: 5882. PMID: 37735172, PMCID: PMC10514346, DOI: 10.1038/s41467-023-41614-x.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisExtracellular matrix invasionLung fibroblastsIdiopathic pulmonary fibrosis patientsIdiopathic pulmonary fibrosisPulmonary fibrosis patientsMatrix invasionPromising therapeutic optionProfibrotic milieuTherapeutic optionsLung tissuePathogenic hallmarkPharmacological targetingFibrosisFibrosis patientsIncurable diseaseEx vivoBleomycinExtracellular matrix componentsTks5 expressionAberrant depositionInvasionMiceFibroblastsSrc kinase
2022
Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
Fernández-Castañeda A, Lu P, Geraghty AC, Song E, Lee MH, Wood J, O'Dea MR, Dutton S, Shamardani K, Nwangwu K, Mancusi R, Yalçın B, Taylor KR, Acosta-Alvarez L, Malacon K, Keough MB, Ni L, Woo PJ, Contreras-Esquivel D, Toland AMS, Gehlhausen JR, Klein J, Takahashi T, Silva J, Israelow B, Lucas C, Mao T, Peña-Hernández MA, Tabachnikova A, Homer RJ, Tabacof L, Tosto-Mancuso J, Breyman E, Kontorovich A, McCarthy D, Quezado M, Vogel H, Hefti MM, Perl DP, Liddelow S, Folkerth R, Putrino D, Nath A, Iwasaki A, Monje M. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell 2022, 185: 2452-2468.e16. PMID: 35768006, PMCID: PMC9189143, DOI: 10.1016/j.cell.2022.06.008.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMicroglial reactivityCognitive impairmentCSF cytokines/chemokinesCytokines/chemokinesSARS-CoV-2Early time pointsCCL11 levelsMild COVIDRespiratory influenzaHippocampal neurogenesisOligodendrocyte lossHippocampal pathologyMyelin lossNeurological symptomsImpaired neurogenesisCOVID survivorsNeurobiological effectsNeural dysregulationMyelin dysregulationCCL11Neural cellsTime pointsNeurogenesisMice
2021
Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma
Robles-Oteiza C, Ayeni D, Levy S, Homer RJ, Kaech SM, Politi K. Elevated murine HB-EGF confers sensitivity to diphtheria toxin in EGFR-mutant lung adenocarcinoma. Disease Models & Mechanisms 2021, 14: dmm049072. PMID: 34494649, PMCID: PMC8617309, DOI: 10.1242/dmm.049072.Peer-Reviewed Original ResearchConceptsHuman diphtheria toxin receptorDiphtheria toxin receptorTumor regressionEGFR-mutant lung cancerEGFR-mutant lung adenocarcinomaEGFR-mutant tumorsMutant EGFRTissue-specific promotorsFVB miceLung cancerSystemic administrationLung adenocarcinomaMurine lungRapid regressionConditional ablationTumor cellsUpregulated expressionMiceElevated expressionToxin receptorHB-EGFCell populationsHBEGFEGFRPrimary target
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMice
2017
Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function
Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo e Drigo R, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nature Medicine 2017, 24: 39-49. PMID: 29200204, PMCID: PMC5760280, DOI: 10.1038/nm.4447.Peer-Reviewed Original ResearchZika virus causes testicular atrophy
Uraki R, Hwang J, Jurado KA, Householder S, Yockey LJ, Hastings AK, Homer RJ, Iwasaki A, Fikrig E. Zika virus causes testicular atrophy. Science Advances 2017, 3: e1602899. PMID: 28261663, PMCID: PMC5321463, DOI: 10.1126/sciadv.1602899.Peer-Reviewed Original ResearchConceptsZika virusTesticular atrophyAcute viremic phaseZIKV-infected miceMosquito-borne flavivirusTestosterone-producing Leydig cellsProgressive testicular atrophyZIKV persistenceFetal infectionViremic phaseNeonatal abnormalitiesSerum testosteroneZIKV infectionNeurological dysfunctionSubcutaneous injectionZIKV replicationLeydig cellsVirus replicationVertical transmissionEpithelial cellsMiceViral RNAReproductive deficienciesAtrophyMale fertility
2016
Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza
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 expressionInhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4
Jiang D, Liang J, Campanella GS, Guo R, Yu S, Xie T, Liu N, Jung Y, Homer R, Meltzer EB, Li Y, Tager AM, Goetinck PF, Luster AD, Noble PW. Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4. Journal Of Clinical Investigation 2010, 120: 2049-2057. PMID: 20484822, PMCID: PMC2877927, DOI: 10.1172/jci38644.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisCXCL10 proteinAcute lung injuryExcess extracellular matrix productionLung fibroblast migrationSyndecan-4Myofibroblast recruitmentLung injuryLung functionSubsequent fibrosisNeutrophil recruitmentInterstitial fibrosisWT miceIntratracheal instillationSyndecan-4 expressionNovel therapiesMigration of fibroblastsFibrosisBleomycin treatmentCXCL10Fibroblast recruitmentExtracellular matrix productionHeparan sulfate proteoglycan syndecan-4Interstitial compartmentMiceAirway epithelium response to IFN-γ regulates allergic airway inflammation (91.7)
Mitchell C, Provost K, Niu N, Homer R, Cohn L. Airway epithelium response to IFN-γ regulates allergic airway inflammation (91.7). The Journal Of Immunology 2010, 184: 91.7-91.7. DOI: 10.4049/jimmunol.184.supp.91.7.Peer-Reviewed Original ResearchAirway epithelial cellsAllergic airway inflammationAllergic airway diseaseAirway eosinophiliaAirway inflammationAirway diseaseNon-hematopoietic cellsEpithelial cellsIFN-γRIFN-γ receptor-deficient miceIFN-γR expressionReceptor-deficient miceBone marrow chimerasOVA-specific Th1Th1 cellsDeficient miceMucus productionBone marrowEpithelium responseIFNMaximal inhibitionEosinophiliaInflammationMiceInhibitory effect
2009
Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2- Dependent Allergic Airway Inflammation
Niu N, Laufer T, Homer RJ, Cohn L. Cutting Edge: Limiting MHC Class II Expression to Dendritic Cells Alters the Ability to Develop Th2- Dependent Allergic Airway Inflammation. The Journal Of Immunology 2009, 183: 1523-1527. PMID: 19596982, DOI: 10.4049/jimmunol.0901349.Peer-Reviewed Original ResearchConceptsAllergic airway inflammationMHC class II expressionAirway inflammationDendritic cellsClass II expressionTh2 generationTh2 immunityTh2-dependent allergic airway inflammationTh1 immune responseIFN-gamma productionAirway neutrophiliaTh2 primingRespiratory tractTh2 cellsImmune responseClass II signalsInflammationTh2 recruitmentMice resultsMiceCells altersImmunityActivationCellsNeutrophiliaRole of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13–induced tissue responses and apoptosis
Lee CG, Hartl D, Lee GR, Koller B, Matsuura H, Da Silva CA, Sohn MH, Cohn L, Homer RJ, Kozhich AA, Humbles A, Kearley J, Coyle A, Chupp G, Reed J, Flavell RA, Elias JA. Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13–induced tissue responses and apoptosis. Journal Of Experimental Medicine 2009, 206: 1149-1166. PMID: 19414556, PMCID: PMC2715037, DOI: 10.1084/jem.20081271.Peer-Reviewed Original ResearchConceptsBRP-39/YKLBreast regression protein 39YKL-40BRP-39Th2 responsesIL-13-induced tissue responsesDendritic cell accumulationAlternative macrophage activationApoptosis/cell deathProtein 39Protein kinase B/AktTh2 inflammationDisease activityAntigen sensitizationEffector phaseTissue inflammationExaggerated quantitiesPulmonary epitheliumTherapeutic targetMacrophage activationTransgenic miceCell accumulationFas expressionNovel regulatory roleMice
2007
Inhibition of NF-κB Activation Reduces the Tissue Effects of Transgenic IL-13
Chapoval SP, Al-Garawi A, Lora JM, Strickland I, Ma B, Lee PJ, Homer RJ, Ghosh S, Coyle AJ, Elias JA. Inhibition of NF-κB Activation Reduces the Tissue Effects of Transgenic IL-13. The Journal Of Immunology 2007, 179: 7030-7041. PMID: 17982094, DOI: 10.4049/jimmunol.179.10.7030.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsApoptosisCaspasesHeterocyclic Compounds, 3-RingI-kappa B KinaseInflammationInhibitor of Apoptosis ProteinsInterleukin-13MiceMice, Mutant StrainsMice, TransgenicMucusNF-kappa B p50 SubunitPeptidesPulmonary AlveoliPulmonary FibrosisPyridinesReceptors, Cell SurfaceRespiratory HypersensitivitySignal TransductionTh2 CellsConceptsTransgenic IL-13IL-13Alveolar remodelingIL-13 transgenic miceNF-kappaBMajor Th2 cytokinesExcessive mucus productionTissue effectsNF-κB activationNF-kappaB activationNF-kappaB activityNF-kappaB componentsAirway hyperresponsivenessTh2 cytokinesTissue inflammationPharmacologic approachesMucus productionIL-13Ralpha1Murine lungSmall molecule inhibitorsTissue alterationsNF-kappaB.MiceCell apoptosisDiminished levelsIL-18 Is Induced and IL-18 Receptor α Plays a Critical Role in the Pathogenesis of Cigarette Smoke-Induced Pulmonary Emphysema and Inflammation
Kang MJ, Homer RJ, Gallo A, Lee CG, Crothers KA, Cho SJ, Rochester C, Cain H, Chupp G, Yoon HJ, Elias JA. IL-18 Is Induced and IL-18 Receptor α Plays a Critical Role in the Pathogenesis of Cigarette Smoke-Induced Pulmonary Emphysema and Inflammation. The Journal Of Immunology 2007, 178: 1948-1959. PMID: 17237446, DOI: 10.4049/jimmunol.178.3.1948.Peer-Reviewed Original ResearchConceptsChronic obstructive lung diseaseObstructive lung diseaseIL-18Wild-type miceCigarette smokeLung diseasePulmonary emphysemaIL-18RalphaPathogenesis of CSEffects of CSAir-exposed miceIL-18 pathwayIL-18 receptor αIL-18R signalingTh1 inflammationPulmonary macrophagesEpithelial apoptosisReceptor αInflammationPotent stimulatorEmphysemaCaspase-1MiceCritical roleElevated levels
2006
Essential 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 mutationRole of Early Growth Response-1 (Egr-1) in Interleukin-13-induced Inflammation and Remodeling*
Cho SJ, Kang MJ, Homer RJ, Kang HR, Zhang X, Lee PJ, Elias JA, Lee CG. Role of Early Growth Response-1 (Egr-1) in Interleukin-13-induced Inflammation and Remodeling*. Journal Of Biological Chemistry 2006, 281: 8161-8168. PMID: 16439363, DOI: 10.1074/jbc.m506770200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar LavageCaspasesCell DeathCollagenDNAEarly Growth Response Protein 1Enzyme InhibitorsFibrosisFlavonoidsImmunoblottingIn Situ Nick-End LabelingInflammationInterleukin-13LungMatrix Metalloproteinase 9MiceMice, Inbred C57BLMice, TransgenicMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Models, BiologicalModels, StatisticalRNARNA, MessengerSTAT6 Transcription FactorTh2 CellsTime FactorsTransforming Growth Factor betaTransforming Growth Factor beta1TransgenesConceptsIL-13Early growth response 1IL-13-induced tissue responsesEgr-1Transgenic IL-13Matrix metalloproteinase-9Wild-type miceResponse 1Th2 inflammationCXC chemokinesMetalloproteinase-9Type miceMetalloproteinase-1Transgenic miceAlveolar remodelingTissue inhibitorInflammationPotent stimulatorImportant stimulatorMiceTissue effectsKey roleTissue responsePathogenesisApoptosis regulator
2005
Cutting Edge: TLR4 Deficiency Confers Susceptibility to Lethal Oxidant Lung Injury
Zhang X, Shan P, Qureshi S, Homer R, Medzhitov R, Noble PW, Lee PJ. Cutting Edge: TLR4 Deficiency Confers Susceptibility to Lethal Oxidant Lung Injury. The Journal Of Immunology 2005, 175: 4834-4838. PMID: 16210584, DOI: 10.4049/jimmunol.175.8.4834.Peer-Reviewed Original ResearchConceptsTLR4-deficient miceLung injuryAntioxidant gene heme oxygenase-1Gene heme oxygenase-1Oxidant lung injuryBcl-2Heme oxygenase-1Life-sustaining measuresPhospho-Akt levelsNovel mechanistic linkRespiratory failureIll patientsLung integrityMurine modelOxygenase-1Oxidant stressProtective roleHost responseInnate immunityInjuryPhospho-AktHyperoxiaConfer susceptibilityMiceMammalian TLR4Chitinases and chitinase-like proteins in TH2 inflammation and asthma
Elias JA, Homer RJ, Hamid Q, Lee CG. Chitinases and chitinase-like proteins in TH2 inflammation and asthma. Journal Of Allergy And Clinical Immunology 2005, 116: 497-500. PMID: 16159614, DOI: 10.1016/j.jaci.2005.06.028.Peer-Reviewed Original ResearchBcl-2–related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury
He CH, Waxman AB, Lee CG, Link H, Rabach ME, Ma B, Chen Q, Zhu Z, Zhong M, Nakayama K, Nakayama KI, Homer R, Elias JA. Bcl-2–related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury. Journal Of Clinical Investigation 2005, 115: 1039-1048. PMID: 15841185, PMCID: PMC1070412, DOI: 10.1172/jci23004.Peer-Reviewed Original ResearchConceptsHyperoxic acute lung injuryAcute lung injuryLung injuryIL-11Bcl-2Alveolar protein leakBcl-xLToxic effectsEpithelial cell apoptosisWT miceProtein leakMurine survivalExpression of A1Survival advantageBfl-1/A1Protective responsePremature deathHyperoxiaA1 overexpressionBcl-2 proteinMiceCell apoptosisCritical mediatorInjuryNecrosisIL-11 Receptor α in the Pathogenesis of IL-13-Induced Inflammation and Remodeling
Chen Q, Rabach L, Noble P, Zheng T, Lee CG, Homer RJ, Elias JA. IL-11 Receptor α in the Pathogenesis of IL-13-Induced Inflammation and Remodeling. The Journal Of Immunology 2005, 174: 2305-2313. PMID: 15699166, DOI: 10.4049/jimmunol.174.4.2305.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokines, CCFibroblastsHyaluronic AcidHyperoxiaInflammationInterleukin-11Interleukin-11 Receptor alpha SubunitInterleukin-13Interleukin-13 Receptor alpha1 SubunitLungMatrix MetalloproteinasesMetaplasiaMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMucinsProtein SubunitsPulmonary AlveoliPulmonary FibrosisReceptors, InterleukinReceptors, Interleukin-11Receptors, Interleukin-13Respiratory InsufficiencySignal TransductionTransforming Growth Factor betaTransforming Growth Factor beta1ConceptsIL-13-induced inflammationIL-13IL-11IL-11RalphaIL-13-induced tissue responsesPotent stimulatorTransgenic IL-13Tissue effectsWild-type miceHyaluronic acid accumulationMucus metaplasiaTh2 inflammationRespiratory failureInflammatory disordersGob-5Major stimulatorCC chemokinesMyofibroblast accumulationInflammationTransgenic miceAlveolar remodelingReceptor αMatrix metalloproteinasesMiceDependent pathway