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 ResearchConceptsSuppressor 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 alterationsMacrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. Journal Of Clinical Investigation 2021, 131: e136542. PMID: 33393489, PMCID: PMC7773383, DOI: 10.1172/jci136542.Peer-Reviewed Original ResearchConceptsNetrin-1Lung fibrosisCell-specific knockout miceΑ1-adrenoreceptor blockadeIPF lung tissueNeuronal guidance proteinsNetrin-1 expressionExtracellular matrix accumulationAdrenergic processesAdrenoreceptor antagonismAdrenoreceptor blockadeFibrotic histologyInflammatory scarringIPF cohortAdrenergic nervesΑ1-blockersImproved survivalColorectal carcinomaLung tissueKnockout miceCollagen accumulationFibrosisMatrix accumulationMacrophagesGuidance proteins
2020
Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis
Jiang R, Hoehn KB, Lee CS, Pham MC, Homer RJ, Detterbeck FC, Aban I, Jacobson L, Vincent A, Nowak RJ, Kaminski HJ, Kleinstein SH, O'Connor KC. Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30649-30660. PMID: 33199596, PMCID: PMC7720237, DOI: 10.1073/pnas.2007206117.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutoantibodiesBiomarkersB-LymphocytesClonal EvolutionClonal Selection, Antigen-MediatedDisease SusceptibilityFemaleHumansLymphocyte CountMaleMiddle AgedModels, BiologicalMyasthenia GravisRadioimmunoassayReceptors, CholinergicThymectomyThymus GlandV(D)J RecombinationYoung AdultConceptsB cell clonesMyasthenia gravisB cell repertoireB cellsCell clonesPlasma cellsCell repertoireAdditional immunosuppressive treatmentDiminished clinical responseThymic lymphofollicular hyperplasiaComplete stable remissionMajority of patientsAntigen-experienced B cellsRandomized clinical trialsClinical symptom measuresAChR autoantibodiesImmunosuppressive treatmentSteroid doseAutoantibody titersMG thymusClinical responseStable remissionClinical scoresAutoimmune diseasesClinical trialsMouse 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 diseaseMiceDrug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations
Starrett JH, Guernet AA, Cuomo ME, Poels KE, van Alderwerelt van Rosenburgh IK, Nagelberg A, Farnsworth D, Price KS, Khan H, Ashtekar KD, Gaefele M, Ayeni D, Stewart TF, Kuhlmann A, Kaech S, Unni AM, Homer R, Lockwood WW, Michor F, Goldberg SB, Lemmon MA, Smith PD, Cross D, Politi K. Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance EGFR Mutations. Cancer Research 2020, 80: 2017-2030. PMID: 32193290, PMCID: PMC7392201, DOI: 10.1158/0008-5472.can-19-3819.Peer-Reviewed Original ResearchConceptsOsimertinib resistancePreferred first-line therapyThird-generation EGFR tyrosine kinase inhibitorEGFR tyrosine kinase inhibitorsResistance EGFR mutationsFirst-line therapyMutant lung cancerFirst-line osimertinibSubsequent treatment approachesTransgenic mouse modelTyrosine kinase inhibitorsSecondary mutationsErlotinib treatmentLung cancerEGFR mutationsLung adenocarcinomaMouse modelTherapeutic strategiesTherapeutic testingTreatment approachesMutant tumorsResistance mutationsDrug sensitivityDriver mutationsKinase inhibitors
2019
A Semiquantitative Scoring System May Allow Biopsy Diagnosis of Pulmonary Large Cell Neuroendocrine Carcinoma
Baine MK, Sinard JH, Cai G, Homer RJ. A Semiquantitative Scoring System May Allow Biopsy Diagnosis of Pulmonary Large Cell Neuroendocrine Carcinoma. American Journal Of Clinical Pathology 2019, 153: 165-174. PMID: 31593583, PMCID: PMC7571487, DOI: 10.1093/ajcp/aqz149.Peer-Reviewed Original ResearchReanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, Roden AC, Hirsch FR, Wistuba II, Pusztai L. Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer. Breast Cancer Research 2019, 21: 72. PMID: 31196152, PMCID: PMC6567382, DOI: 10.1186/s13058-019-1156-6.Peer-Reviewed Original ResearchConceptsPD-L1 expressionImmune cell PD-L1 expressionLung cancerImmune cellsTriple-negative breast cancerEasy scoring methodCompanion diagnostic testsPD-L1Immune therapyBreast cancerImmunohistochemical testsBetter outcomesLarger studyTumor cellsDiagnostic testsCancerExpression findingsCellsExpressionPoor agreementScoring methodTherapyTrials
2018
A rare presentation of pulmonary sarcoidosis as a solitary lung mass: a case report
Kelleher DW, Yaggi M, Homer R, Herzog EL, Ryu C. A rare presentation of pulmonary sarcoidosis as a solitary lung mass: a case report. Journal Of Medical Case Reports 2018, 12: 94. PMID: 29650028, PMCID: PMC5897926, DOI: 10.1186/s13256-018-1632-0.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSolitary lung massPulmonary sarcoidosisBroad differential diagnosisLung massConstitutional symptomsHilar lymphadenopathyRadiographic featuresDifferential diagnosisLarge left lower lobe massStage II pulmonary sarcoidosisComputed tomography-guided biopsyType 2 diabetes mellitusHigh-dose prednisoneLower lobe massTomographic scan findingsMonths of therapyUnintentional weight lossEvidence of malignancySarcoid-like reactionTomography-guided biopsyShortness of breathNon-necrotizing granulomasChronic granulomatous diseaseAfrican American womenOccult malignancy
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 ResearchUpper Airway Obstruction Requiring Emergent Tracheostomy Secondary to Laryngeal Sarcoidosis: A Case Report
Ryu C, Herzog EL, Pan H, Homer R, Gulati M. Upper Airway Obstruction Requiring Emergent Tracheostomy Secondary to Laryngeal Sarcoidosis: A Case Report. American Journal Of Case Reports 2017, 18: 157-159. PMID: 28190872, PMCID: PMC5319306, DOI: 10.12659/ajcr.902231.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsUpper airway obstructionRare extrapulmonary manifestationLaryngeal sarcoidosisLife-threatening complicationsAirway obstructionEmergent tracheostomyExtrapulmonary manifestationsCase reportComplete upper airway obstructionLow-dose prednisoneMonths of corticosteroidsStage 1 sarcoidosisAddition of methotrexateAfrican American femalesTapered dosageRespiratory failureSevere dyspneaInspiratory stridorSignificant morbidityPhysical examinationChronic careAryepiglottic foldsTimely diagnosisSarcoidosisPrednisone
2016
Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice
Sureshbabu A, Syed M, Das P, Janér C, Pryhuber G, Rahman A, Andersson S, Homer RJ, Bhandari V. Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice. American Journal Of Respiratory Cell And Molecular Biology 2016, 55: 722-735. PMID: 27374190, PMCID: PMC5105179, DOI: 10.1165/rcmb.2015-0349oc.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAdaptor Proteins, Signal TransducingAlveolar Epithelial CellsAnimalsAnimals, NewbornApoptosisAutophagyBronchopulmonary DysplasiaCell LineFemaleHumansHyperoxiaHypertension, PulmonaryHypertrophy, Right VentricularInfant, NewbornLungMiceMicrotubule-Associated ProteinsNaphthyridinesPhenotypeRegulatory-Associated Protein of mTORTime FactorsTumor Suppressor Protein p53ConceptsAcute lung injuryBronchopulmonary dysplasiaLung injuryWild-type miceMechanistic targetRegulatory-Associated ProteinLysosomal-associated membrane protein 1Apoptotic cell deathFetal type II alveolar epithelial cellsMouse lungRole of autophagyHyperoxia-Induced Lung InjuryLight chain 3Activation of autophagyType II alveolar epithelial cellsRespiratory distress syndromeMembrane protein 1Developmental lung diseaseUseful therapeutic targetNeonatal mouse lungAlveolar epithelial cellsPharmacological inhibitorsTreatment of hyperoxiaCell deathAutophagic fluxMx1 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 geneHumansMonocytesMortalityInfluenzaEndobronchial Ultrasound-Guided Cautery-Assisted Transbronchial Forceps Biopsies: Safety and Sensitivity Relative to Transbronchial Needle Aspiration
Bramley K, Pisani MA, Murphy TE, Araujo KL, Homer RJ, Puchalski JT. Endobronchial Ultrasound-Guided Cautery-Assisted Transbronchial Forceps Biopsies: Safety and Sensitivity Relative to Transbronchial Needle Aspiration. The Annals Of Thoracic Surgery 2016, 101: 1870-1876. PMID: 26912301, PMCID: PMC4861078, DOI: 10.1016/j.athoracsur.2015.11.051.Peer-Reviewed Original ResearchConceptsTransbronchial needle aspirationTransbronchial forceps biopsyForceps biopsyClinical trialsEndobronchial ultrasoundNeedle aspirationConvex probe EBUSSignificant adverse eventsDiagnosis of sarcoidosisExcellent diagnostic yieldSelect clinical scenariosSequential useTBNA samplesSecondary outcomesUnselected patientsAdverse eventsLymph nodesThoracic lymphadenopathyEBUS guidanceGranulomatous inflammationCore biopsyGranulomatous diseaseAdequate specimensNeedle biopsyDiagnostic yieldRole of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs
Syed MA, Choo-Wing R, Homer RJ, Bhandari V. Role of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs. PLOS ONE 2016, 11: e0147588. PMID: 26799210, PMCID: PMC4723240, DOI: 10.1371/journal.pone.0147588.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorEndothelial growth factorVascular markersRoom airVascular permeabilityMouse lungLung developmentVEGF overexpressionDifferent nitric oxide synthase isoformsNitric oxide synthase isoformsGrowth factorInhibition of NOS1Inhibition of NOS2Nitric oxide isoformsOxidative stress markersNeonatal mouse lungNOS1 inhibitionNOS1 inhibitorInjury markersLung injuryLung vascularNewborn lungNOS pathwayAlveolar developmentPostnatal dayComparison of Transbronchial and Cryobiopsies in Evaluation of Diffuse Parenchymal Lung Disease
Ramaswamy A, Homer R, Killam J, Pisani MA, Murphy TE, Araujo K, Puchalski J. Comparison of Transbronchial and Cryobiopsies in Evaluation of Diffuse Parenchymal Lung Disease. Journal Of Bronchology & Interventional Pulmonology 2016, 23: 14-21. PMID: 26705007, PMCID: PMC4864578, DOI: 10.1097/lbr.0000000000000246.Peer-Reviewed Original ResearchConceptsDiffuse parenchymal lung diseaseTransbronchial lung cryobiopsyTransbronchial lung biopsyParenchymal lung diseaseLung diseaseFlexible bronchoscopyDiagnostic yieldTertiary care academic centerVideo-assisted thoracoscopic surgeryInterstitial lung diseaseHigh diagnostic yieldTBLB specimensLung biopsyLung cryobiopsyMassive hemoptysisPrior malignancyThoracoscopic surgeryClinicopathologic featuresHypersensitivity pneumonitisModerate sedationRetrospective studyTherapeutic optionsMean ageFinal diagnosisPostprocedural outcomes
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 effects
2014
IL-6 Receptor α Defines Effector Memory CD8+ T Cells Producing Th2 Cytokines and Expanding in Asthma
Lee N, You S, Shin MS, Lee WW, Kang KS, Kim SH, Kim WU, Homer RJ, Kang MJ, Montgomery RR, Dela Cruz CS, Shaw AC, Lee PJ, Chupp GL, Hwang D, Kang I. IL-6 Receptor α Defines Effector Memory CD8+ T Cells Producing Th2 Cytokines and Expanding in Asthma. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 1383-1394. PMID: 25390970, PMCID: PMC4299645, DOI: 10.1164/rccm.201403-0601oc.Peer-Reviewed Original ResearchConceptsEffector memory CD8EM CD8T cellsPeripheral bloodMemory CD8IL-13IL-5IL-6RαTh2-type cytokine IL-5Different T cell subsetsLevels of GATA3Frequency of ILT cell subsetsTh2-type cytokinesHealthy control subjectsRespiratory syncytial virusT cell populationsCytokines IL-5IL-6 receptor αIL-6Rα expressionHuman peripheral bloodEffector CD8Syncytial virusTh2 cytokinesCell subsetsChitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis
Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCHI3L1 levelsChitinase 3Lungs of patientsAlternative macrophage activationLevel of apoptosisAcute exacerbationFibroproliferative repairLung transplantationDisease exacerbationInjury phaseAmbulatory patientsEpithelial injuryPulmonary fibrosisIPF populationLung fibrosisMacrophage accumulationCHI3L1 expressionFibrotic phaseDisease progressionProfibrotic roleFibroproliferative responseMacrophage activationMyofibroblast transformationProtective role
2013
Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma
Cai G, Wong R, Chhieng D, Levy GH, Gettinger SN, Herbst RS, Puchalski JT, Homer RJ, Hui P. Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma. Cancer Cytopathology 2013, 121: 500-507. PMID: 23495083, DOI: 10.1002/cncy.21288.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAnaplastic Lymphoma KinaseBiomarkers, TumorBone NeoplasmsCytodiagnosisDNA, NeoplasmErbB ReceptorsFeasibility StudiesFemaleGene RearrangementHumansIn Situ Hybridization, FluorescenceLiver NeoplasmsLung NeoplasmsMaleMiddle AgedMutationNeoplasm Recurrence, LocalPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsReal-Time Polymerase Chain ReactionReceptor Protein-Tyrosine KinasesSoft Tissue NeoplasmsYoung AdultConceptsALK gene rearrangementMetastatic lung adenocarcinomaEGFR mutationsKRAS mutationsMetastatic tumorsEpidermal growth factor receptorLung adenocarcinomaCytological specimensGene rearrangementsMolecular testsMolecular alterationsKirsten rat sarcoma viral oncogene homolog (KRAS) mutationsALK gene rearrangement analysisAnaplastic lymphoma kinase (ALK) gene rearrangementEGFR T790M mutationRat sarcoma viral oncogene homolog mutationsCases of lungT790M mutationImportant therapeutic implicationsFine needle aspiratesGene rearrangement analysisCell block materialGrowth factor receptorRecurrent lungRecurrent adenocarcinoma
2011
Molecular classification of nonsmall cell lung cancer using a 4‐protein quantitative assay
Anagnostou VK, Dimou AT, Botsis T, Killiam EJ, Gustavson MD, Homer RJ, Boffa D, Zolota V, Dougenis D, Tanoue L, Gettinger SN, Detterbeck FC, Syrigos KN, Bepler G, Rimm DL. Molecular classification of nonsmall cell lung cancer using a 4‐protein quantitative assay. Cancer 2011, 118: 1607-1618. PMID: 22009766, DOI: 10.1002/cncr.26450.Peer-Reviewed Original Research