2021
Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma
Foggetti G, Li C, Cai H, Hellyer JA, Lin WY, Ayeni D, Hastings K, Choi J, Wurtz A, Andrejka L, Maghini DG, Rashleigh N, Levy S, Homer R, Gettinger SN, Diehn M, Wakelee HA, Petrov DA, Winslow MM, Politi K. Genetic Determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In VivoTumor Suppressor Genes and EGFR-Driven Lung Adenocarcinoma. Cancer Discovery 2021, 11: 1736-1753. PMID: 33707235, PMCID: PMC8530463, DOI: 10.1158/2159-8290.cd-20-1385.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAdenocarcinoma of LungAniline CompoundsAnimalsAntineoplastic AgentsDisease Models, AnimalErbB ReceptorsFemaleHumansLung NeoplasmsMaleMiceConceptsSuppressor geneKey tumor suppressorPutative tumor suppressor geneTumor suppressor geneSensitivity of EGFRTumor growthOncogenic contextTumor suppressorHuman EGFRGenetic determinantsKeap1 pathwayComplex genotypesTumor suppressor gene alterationsLung cancer growthGenesDeficient lung adenocarcinomaLung adenocarcinomaGenetic alterationsIssue featureStrong driverCancer growthEGFR inhibitorsKinase inhibitorsInactivationGene alterations
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
2019
Low ambient humidity impairs barrier function and innate resistance against influenza infection
Kudo E, Song E, Yockey LJ, Rakib T, Wong PW, Homer RJ, Iwasaki A. Low ambient humidity impairs barrier function and innate resistance against influenza infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 10905-10910. PMID: 31085641, PMCID: PMC6561219, DOI: 10.1073/pnas.1902840116.Peer-Reviewed Original ResearchConceptsInfluenza infectionImpair barrier functionImpairs host defenseSeasonal influenza virusesInfluenza virus infectionLungs of miceImpairs mucociliary clearanceTissue repairInduction of IFNInnate antiviral defenseViral burdenMucociliary clearanceDisease outcomeRespiratory challengeVirus infectionSevere diseaseViral infectionCongenic miceHost responseViral transmissionHost defenseSingle-cell RNA sequencingInnate resistanceDisease pathologyInfluenza virus
2016
SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis
Tzouvelekis A, Yu G, Lino Cardenas CL, Herazo-Maya JD, Wang R, Woolard T, Zhang Y, Sakamoto K, Lee H, Yi JS, DeIuliis G, Xylourgidis N, Ahangari F, Lee PJ, Aidinis V, Herzog EL, Homer R, Bennett AM, Kaminski N. SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2016, 195: 500-514. PMID: 27736153, PMCID: PMC5378419, DOI: 10.1164/rccm.201602-0329oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisProfibrotic stimuliLung fibroblastsChronic fatal lung diseaseMyofibroblast differentiationPrimary human lung fibroblastsFatal lung diseaseNovel therapeutic strategiesVivo therapeutic effectPotential therapeutic usefulnessHuman lung fibroblastsMouse lung fibroblastsDismal prognosisFibroblastic fociLung fibrosisLung diseaseBleomycin modelTherapeutic effectTherapeutic usefulnessTherapeutic strategiesTherapeutic targetTransgenic miceFibrosisSHP2 overexpressionPlexin 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
2015
Suppression of NLRX1 in chronic obstructive pulmonary disease
Kang MJ, Yoon CM, Kim BH, Lee CM, Zhou Y, Sauler M, Homer R, Dhamija A, Boffa D, West AP, Shadel GS, Ting JP, Tedrow JR, Kaminski N, Kim WJ, Lee CG, Oh YM, Elias JA. Suppression of NLRX1 in chronic obstructive pulmonary disease. Journal Of Clinical Investigation 2015, 125: 2458-2462. PMID: 25938787, PMCID: PMC4497738, DOI: 10.1172/jci71747.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseObstructive pulmonary diseaseCigarette smokeAlveolar destructionPulmonary diseaseHuman chronic obstructive pulmonary diseaseExpression of NLRX1Innate immune pathwaysInnate immune responseQuality of lifeCOPD patientsPulmonary functionSubsequent inflammationImmune responseInflammasome activationMurine modelIndependent cohortImmune pathwaysInflammationDisease severityInflammasome responseImportant mediatorCell apoptosisNLRX1Tissue effectsConditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung
Sureshbabu A, Syed MA, Boddupalli CS, Dhodapkar MV, Homer RJ, Minoo P, Bhandari V. Conditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung. Respiratory Research 2015, 16: 4. PMID: 25591994, PMCID: PMC4307226, DOI: 10.1186/s12931-014-0162-6.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAlveolar Epithelial CellsAnimalsAnimals, NewbornApoptosisDisease Models, AnimalGenotypeHumansHyperoxiaLungMice, Inbred C57BLMice, KnockoutMice, TransgenicPhenotypePneumoniaProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSignal TransductionTime FactorsTransforming Growth Factor beta1Up-RegulationConceptsImpaired alveolarizationBronchopulmonary dysplasiaAlveolar epithelial cellsPulmonary inflammationPulmonary phenotypeMouse lungAcute lung injuryType II alveolar epithelial cellsApoptotic cell deathCell deathNewborn mouse lungPotential therapeutic strategyGrowth factor betaNull mutant miceLung injuryImproved survivalNeonatal mortalityMonocyte infiltrationAbnormal alveolarizationAngiogenic mediatorsInflammatory signalsTGFβ1 expressionTherapeutic strategiesInflammatory macrophagesLung morphometry
2013
Role of Tissue Protection in Lethal Respiratory Viral-Bacterial Coinfection
Jamieson AM, Pasman L, Yu S, Gamradt P, Homer RJ, Decker T, Medzhitov R. Role of Tissue Protection in Lethal Respiratory Viral-Bacterial Coinfection. Science 2013, 340: 1230-1234. PMID: 23618765, PMCID: PMC3933032, DOI: 10.1126/science.1233632.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaspase 1CoinfectionDisease Models, AnimalHost-Pathogen InteractionsInterleukin-1betaLegionella pneumophilaLegionnaires' DiseaseLungMiceMice, Inbred C57BLOrthomyxoviridaeOrthomyxoviridae InfectionsPneumonia, BacterialToll-Like Receptor 2Toll-Like Receptor 3Toll-Like Receptor 4Tumor Necrosis Factor-alphaConceptsHost defenseInfluenza virusImmune resistance mechanismsSecondary bacterial pneumoniaInfluenza virus infectionViral-bacterial coinfectionsBacterial coinfectionBacterial pneumoniaVirus infectionMouse modelTissue protectionImmune systemTissue damagePathogen burdenDisease severityBacterial infectionsImpaired abilityInfectionCoinfectionResistance mechanismsVirusLegionella pneumophilaMorbidityPneumoniaFailure
2012
Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis
Reilkoff RA, Peng H, Murray LA, Peng X, Russell T, Montgomery R, Feghali-Bostwick C, Shaw A, Homer RJ, Gulati M, Mathur A, Elias JA, Herzog EL. Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2012, 187: 180-188. PMID: 23220917, PMCID: PMC3570653, DOI: 10.1164/rccm.201206-1109oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisRegulatory T cellsProgressive idiopathic pulmonary fibrosisSEMA 7ATGF-β1Pulmonary fibrosisLung fibrosisT cellsMurine lungIL-10Bone marrow-derived cellsAdoptive transfer approachT-cell mediatorsMarrow-derived cellsTransforming Growth Factor-β1Murine lung fibrosisGrowth factor-β1Lung CD4Adoptive transferIL-17AIL-4Disease progressionSemaphorin 7ACD4Mouse model
2011
Role of semaphorin 7a signaling in transforming growth factor β1–induced lung fibrosis and scleroderma‐related interstitial lung disease
Gan Y, Reilkoff R, Peng X, Russell T, Chen Q, Mathai SK, Homer R, Gulati M, Siner J, Elias J, Bucala R, Herzog E. Role of semaphorin 7a signaling in transforming growth factor β1–induced lung fibrosis and scleroderma‐related interstitial lung disease. Arthritis & Rheumatism 2011, 63: 2484-2494. PMID: 21484765, PMCID: PMC3651701, DOI: 10.1002/art.30386.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsInterstitial lung diseaseBone marrow-derived cellsMarrow-derived cellsSemaphorin 7AGrowth factor-β1Lung diseaseLung fibrosisFactor-β1Human peripheral blood mononuclear cellsNormal human peripheral blood mononuclear cellsSemaphorin 7a expressionBone marrow transplantationBlood mononuclear cellsReceptor β1 integrinΒ1 integrinFibrocyte differentiationMarrow transplantationPulmonary fibrosisMononuclear cellsProfibrotic effectsTGFβ1 geneMurine modelFibrosisTissue accumulationModern 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 researchTransplantationLungDiseaseRIG-like Helicase Innate Immunity Inhibits Vascular Endothelial Growth Factor Tissue Responses via a Type I IFN–dependent Mechanism
Ma B, Dela Cruz CS, Hartl D, Kang MJ, Takyar S, Homer RJ, Lee CG, Elias JA. RIG-like Helicase Innate Immunity Inhibits Vascular Endothelial Growth Factor Tissue Responses via a Type I IFN–dependent Mechanism. American Journal Of Respiratory And Critical Care Medicine 2011, 183: 1322-1335. PMID: 21278304, PMCID: PMC3114061, DOI: 10.1164/rccm.201008-1276oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDEAD Box Protein 58DEAD-box RNA HelicasesDisease Models, AnimalEdemaFocal Adhesion Protein-Tyrosine KinasesImmunity, InnateInflammationInterferon Type IMiceMice, TransgenicMitogen-Activated Protein KinasesNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasePoly I-CPulmonary Disease, Chronic ObstructiveToll-Like Receptor 3Vascular Endothelial Growth Factor AConceptsVascular endothelial growth factorType 2 inflammationChronic obstructive pulmonary disease exacerbationsObstructive pulmonary disease exacerbationsChronic obstructive pulmonary diseaseViral pathogen-associated molecular patternsEndothelial nitric oxide synthaseRIG-like helicasePulmonary disease exacerbationsObstructive pulmonary diseasePathogenesis of asthmaRespiratory syncytial virusNormal pulmonary physiologyNitric oxide synthaseAntiviral innate immunityPathogen-associated molecular patternsReceptor-dependent pathwayTissue responseEndothelial growth factorVEGF receptor 1Ability of VEGFDisease exacerbationPulmonary diseaseRespiratory virusesControl miceA 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
Recent advances in pulmonary fibrosis: implications for scleroderma
Homer RJ, Herzog EL. Recent advances in pulmonary fibrosis: implications for scleroderma. Current Opinion In Rheumatology 2010, 22: 683-689. PMID: 20693906, DOI: 10.1097/bor.0b013e32833ddcc9.BooksMeSH KeywordsAnimalsAutoantibodiesDisease Models, AnimalHumansIdiopathic Pulmonary FibrosisInflammationRespiratory MucosaScleroderma, SystemicConceptsPulmonary fibrosisEpithelial cell injuryCell injuryIdiopathic pulmonary fibrosisRole of lymphocytesAlternative macrophage activationPathogenesis of sclerodermaTranslational human studiesEpithelial-mesenchymal transitionEndoplasmic reticulum stressMost patientsSystemic sclerosisLung fibrosisLymphocyte functionEffective therapyLeading causeLung parenchymaFibrotic responseHuman studiesMacrophage activationScar tissueFibrosisPossible associationAnimal modelingPatients
2007
Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma
Simeone-Penney MC, Severgnini M, Tu P, Homer RJ, Mariani TJ, Cohn L, Simon AR. Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma. The Journal Of Immunology 2007, 178: 6191-6199. PMID: 17475846, DOI: 10.4049/jimmunol.178.10.6191.Peer-Reviewed Original ResearchConceptsHouse dust miteAirway epitheliumAllergic inflammationRole of STAT3Murine modelNovel asthma therapiesSignificant decreaseSTAT3 activationTh2 cell recruitmentAcute phase responseWild-type animalsAirway hyperresponsivenessAirway eosinophiliaAirway inflammationAllergic asthmaAsthma therapyChronic asthmaLung inflammationC57BL/6 miceAllergic responsesDust miteEpithelial STAT3Immune cellsSmooth muscleSTAT3 transcription factorA Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract
Niu N, Le Goff MK, Li F, Rahman M, Homer RJ, Cohn L. A Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract. The Journal Of Immunology 2007, 178: 3846-3855. PMID: 17339484, DOI: 10.4049/jimmunol.178.6.3846.Peer-Reviewed Original ResearchConceptsAirway inflammationInflammatory diseasesRespiratory tractTh2-induced airway inflammationChronic airway inflammatory diseaseLymphocyte-deficient miceState of immunosuppressionAcute airway inflammationAirway inflammatory diseasesEffector Th cellsTh2 cells resultsAirway hyperresponsivenessInflammation wanesTh2 modelEffector Th1Respiratory illnessTh cellsInhalational exposureInflammationInhibitory effectSuch diseasesDiseaseStriking inhibitionTh1Localized treatment
2006
IFN-γ–dependent DNA Injury and/or Apoptosis Are Critical in Cigarette Smoke–induced Murine Emphysema
Kang MJ, Lee CG, Cho SJ, Homer RJ, Elias JA. IFN-γ–dependent DNA Injury and/or Apoptosis Are Critical in Cigarette Smoke–induced Murine Emphysema. Annals Of The American Thoracic Society 2006, 3: 517a-518. PMID: 16921135, DOI: 10.1513/pats.200603-075ms.Peer-Reviewed Original ResearchGenetic Control of Transforming Growth Factor-β1–induced Emphysema and Fibrosis in the Murine Lung
Lee CG, Cho S, Homer RJ, Elias JA. Genetic Control of Transforming Growth Factor-β1–induced Emphysema and Fibrosis in the Murine Lung. Annals Of The American Thoracic Society 2006, 3: 476a-477. PMID: 16921114, DOI: 10.1513/pats.200603-040ms.Peer-Reviewed Original ResearchState of the Art. Mechanistic Heterogeneity in Chronic Obstructive Pulmonary Disease
Elias JA, Kang MJ, Crothers K, Homer R, Lee CG. State of the Art. Mechanistic Heterogeneity in Chronic Obstructive Pulmonary Disease. Annals Of The American Thoracic Society 2006, 3: 494-498. PMID: 16921126, DOI: 10.1513/pats.200603-068ms.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseVascular endothelial growth factorSecretory leukocyte proteinase inhibitorTh1/Tc1Obstructive pulmonary diseaseAlveolar destructionIFN-gammaMatrix metalloproteinasesMucus metaplasiaPulmonary diseaseCCR5-dependent mechanismEmphysematous alveolar destructionCigarette smoke exposureCytokine IFN-gammaIFN-gamma responsesEndothelial growth factorApoptosis-independent pathwayCCR5/Pulmonary fibrosisPulmonary responseSmoke exposureIL-13CC chemokinesFibrotic responseMurine lung
2005
Role of Cathepsin S-Dependent Epithelial Cell Apoptosis in IFN-γ-Induced Alveolar Remodeling and Pulmonary Emphysema
Zheng T, Kang MJ, Crothers K, Zhu Z, Liu W, Lee CG, Rabach LA, Chapman HA, Homer RJ, Aldous D, DeSanctis G, Underwood S, Graupe M, Flavell RA, Schmidt JA, Elias JA. Role of Cathepsin S-Dependent Epithelial Cell Apoptosis in IFN-γ-Induced Alveolar Remodeling and Pulmonary Emphysema. The Journal Of Immunology 2005, 174: 8106-8115. PMID: 15944319, DOI: 10.4049/jimmunol.174.12.8106.Peer-Reviewed Original ResearchConceptsNull mutationEpithelial cell apoptosisCell apoptosisDNA injuryTissue remodelingProtease accumulationCaspase inhibitorsMitochondrial apoptosis pathway activationDeath receptorsPropidium iodide stainingCathepsin SHuman diseasesApoptosis responseApoptosis pathway activationApoptosis inhibitionCaspase-3ApoptosisIodide stainingPathway activationCathepsin S inhibitionMutationsRemodelingCritical eventsAlveolar remodelingIFN-gamma