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 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
Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors
Ayeni D, Miller B, Kuhlmann A, Ho PC, Robles-Oteiza C, Gaefele M, Levy S, de Miguel FJ, Perry C, Guan T, Krystal G, Lockwood W, Zelterman D, Homer R, Liu Z, Kaech S, Politi K. Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors. Journal For ImmunoTherapy Of Cancer 2019, 7: 172. PMID: 31291990, PMCID: PMC6617639, DOI: 10.1186/s40425-019-0643-8.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsEGFR-mutant lung cancerMutant lung cancerTumor regressionErlotinib treatmentLung cancerImmune cellsLung tumorsMouse modelEffects of TKIsGrowth factor receptor tyrosine kinase inhibitorsTumor-infiltrating immune cellsDrug resistanceReceptor tyrosine kinase inhibitorsInflammatory immune cellsInflammatory T cellsEffect of erlotinibEGFR mutant lung tumorsInflammatory cellsImmunological profileT cellsCD40 agonistsImmunostimulatory effectsAlveolar macrophagesErlotinib
2016
Increased susceptibility of Cftr−/− mice to LPS-induced lung remodeling
Bruscia E, Zhang P, Barone C, Scholte BJ, Homer R, Krause D, Egan ME. Increased susceptibility of Cftr−/− mice to LPS-induced lung remodeling. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2016, 310: l711-l719. PMID: 26851259, PMCID: PMC4836110, DOI: 10.1152/ajplung.00284.2015.Peer-Reviewed Original ResearchConceptsLung pathologyCF miceImmune responseWT miceChronic inflammationCystic fibrosisAbnormal immune responseChronic pulmonary infectionPersistent immune responseWild-type littermatesCF mouse modelsPseudomonas aeruginosa lipopolysaccharideCF lung pathologyPulmonary infectionChronic administrationLPS exposurePersistent inflammationLung remodelingWT littermatesLung tissueOverall pathologyMouse modelInflammationChronic exposureBacterial products
2014
Thoracic Neoplasia: Carcinoma
Politi K, Dela Cruz C, Homer R. Thoracic Neoplasia: Carcinoma. 2014, 2677-2689. DOI: 10.1016/b978-0-12-386456-7.05310-7.ChaptersLung cancerLung cancer subtypesDifferent natural historyLung cancer biologyCancer deathMolecular subtypesMouse modelNew therapiesSurvival rateCancer subtypesNatural historyLung cancer genomeTumor samplesDiseaseCell linesCancer biologyTherapyOngoing studiesCancerSubtypesRecent knowledgeMolecular mechanismsSpecific subsetPatientsCarcinoma
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
Airway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway
Mijares LA, Wangdi T, Sokol C, Homer R, Medzhitov R, Kazmierczak BI. Airway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway. The Journal Of Immunology 2011, 186: 7080-7088. PMID: 21572023, PMCID: PMC3110630, DOI: 10.4049/jimmunol.1003687.Peer-Reviewed Original ResearchConceptsInnate immune responseImmune responseMyD88-dependent innate immune responsesIL-1-dependent pathwayBone marrow chimeric miceProtective innate immune responseP. aeruginosaNovel transgenic mouse modelVentilator-associated pneumoniaIL-1R signalingTransgenic mouse modelP. aeruginosa infectionEpithelial cell responsesRadio-resistant cellsIntranasal infectionMyD88 expressionMultiple TLR pathwaysMyD88 functionAeruginosa infectionMouse modelTLR pathwayMurine infectionChimeric miceCell responsesInfection
2010
TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P
Murray LA, Chen Q, Kramer MS, Hesson DP, Argentieri RL, Peng X, Gulati M, Homer RJ, Russell T, van Rooijen N, Elias JA, Hogaboam CM, Herzog EL. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. The International Journal Of Biochemistry & Cell Biology 2010, 43: 154-162. PMID: 21044893, DOI: 10.1016/j.biocel.2010.10.013.Peer-Reviewed Original ResearchConceptsSerum amyloid PAnti-fibrotic effectsLung fibrosisFibrocyte accumulationAmyloid PAberrant extracellular matrix (ECM) depositionTransgenic mouse modelM2 macrophage differentiationPleiotropic growth factorExtracellular matrix depositionAirway inflammationIPF patientsAirway remodelingPulmonary fibrosisMacrophage accumulationLung diseaseLiposomal clodronateCXCL10 expressionM2 macrophagesMonocyte responsePulmonary macrophagesMouse modelCollagen depositionPathogenic mechanismsDisease severity
2009
Regression of murine lung tumors by the let-7 microRNA
Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, Homer R, Brown D, Bader AG, Weidhaas JB, Slack FJ. Regression of murine lung tumors by the let-7 microRNA. Oncogene 2009, 29: 1580-1587. PMID: 19966857, PMCID: PMC2841713, DOI: 10.1038/onc.2009.445.Peer-Reviewed Original Research
1999
T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus Production
Cohn L, Homer R, Niu N, Bottomly K. T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus Production. Journal Of Experimental Medicine 1999, 190: 1309-1318. PMID: 10544202, PMCID: PMC2195688, DOI: 10.1084/jem.190.9.1309.Peer-Reviewed Original ResearchConceptsTh1 cellsTh2 cellsMucus productionAirway eosinophiliaIFN-gammaRecipient miceAirway inflammationIFN-gamma receptor signalingT helper type 1T helper 1 cellsAllergic airway inflammationTh2 cytokine secretionHelper type 1Different inhibitory pathwaysAsthmatic patientsPathologic featuresCytokine secretionInflammatory responseRespiratory tractEosinophiliaInhibitory pathwaysMouse modelInflammationType 1Marked reduction