2024
Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.
Trujillo G, Regueiro-Ren A, Liu C, Hu B, Sun Y, Ahangari F, Fiorini V, Ishikawa G, Al Jumaily K, Khoury J, McGovern J, Lee C, Peng X, Pivarnik T, Sun H, Walia A, Woo S, Yu S, Antin-Ozerkis D, Sauler M, Kaminski N, Herzog E, Ryu C. Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024 PMID: 39189851, DOI: 10.1164/rccm.202401-0065oc.Peer-Reviewed Original ResearchToll-like receptor 9Model of pulmonary fibrosisIdiopathic pulmonary fibrosisPulmonary fibrosisFibroproliferative responseLung diseaseIdiopathic pulmonary fibrosis cohortsExpression of toll-like receptor 9Toll-like receptor 9 activationTransplant-free survivalExpression of MCP-1Cohort of patientsSlow clinical progressionFibrotic lung diseaseAccelerated disease courseFatal lung diseaseIP-10Pharmacodynamic endpointsPreclinical modelsDisease courseClinical progressionPlasma mtDNAMCP-1Receptor 9Mouse modelSingle Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Zhao A, Unterman A, Abu Hussein N, Sharma P, Nekola F, Flint J, Yan X, Adams T, Justet A, Sumida T, Zhao J, Schupp J, Raredon M, Ahangari F, Deluliis G, Zhang Y, Buendia-Roldan I, Adegunsoye A, Sperling A, Prasse A, Ryu C, Herzog E, Selman M, Pardo A, Kaminski N. Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2024 PMID: 38924775, DOI: 10.1164/rccm.202401-0078oc.Peer-Reviewed Original ResearchFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsBronchoalveolar lavage cellsBlood mononuclear cellsClassical monocytesHypersensitivity pneumonitisPulmonary fibrosisT cellsImmune perturbationsLavage cellsMononuclear cellsCD8+ T cellsCytotoxic T cellsInterstitial lung diseaseHypersensitivity pneumonitis patientsCytotoxic CD4Immune aberrationsPneumonic patientsPneumonitisLung diseaseHealthy controlsImmune mechanismsPatient cellsSingle-cell transcriptomicsNoninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1
Mannes P, Adams T, Farsijani S, Barnes C, Latoche J, Day K, Nedrow J, Ahangari F, Kaminski N, Lee J, Tavakoli S. Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1. Science Advances 2024, 10: eadm9817. PMID: 38896611, PMCID: PMC11186491, DOI: 10.1126/sciadv.adm9817.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisFibrotic lung diseaseRisk stratificationMurine modelLung fibrosisLung diseaseModel of bleomycin-induced lung fibrosisBleomycin-induced lung fibrosisImaging biomarkersMurine model of bleomycin-induced lung fibrosisBronchoalveolar lavage cellsMonocyte-derived macrophagesPositron emission tomographyInflammatory endotypesPulmonary fibrosisLavage cellsPoor survivalNoninvasive assessmentTherapeutic monitoringEmission tomographyCMKLR1FibrosisClinical trajectoryLungLung regions
2023
Vascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling.
Yanagihara T, Tsubouchi K, Zhou Q, Chong M, Otsubo K, Isshiki T, Schupp J, Sato S, Scallan C, Upagupta C, Revill S, Ayoub A, Chong S, Dvorkin-Gheva A, Kaminski N, Tikkanen J, Keshavjee S, Paré G, Guignabert C, Ask K, Kolb M. Vascular-Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling. American Journal Of Respiratory And Critical Care Medicine 2023, 207: 1498-1514. PMID: 36917778, DOI: 10.1164/rccm.202109-2174oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisVascular smooth muscle cellsAdvanced idiopathic pulmonary fibrosisPulmonary hypertensionFibrotic lungsVascular remodelingEndothelial cellsPulmonary fibrosisLung diseaseLung fibrosisDevelopment of PHConcomitant pulmonary hypertensionProgressive lung scarringPulmonary vascular remodelingFibrotic lung diseaseProgression of fibrosisActivation of VSMCsActive TGF-β1Fatal lung diseaseSmooth muscle cellsWhole-exome sequencingLung scarringEndothelial dysfunctionPoor prognosisFibrogenic effectsRational engineering of lung alveolar epithelium
Leiby K, Yuan Y, Ng R, Raredon M, Adams T, Baevova P, Greaney A, Hirschi K, Campbell S, Kaminski N, Herzog E, Niklason L. Rational engineering of lung alveolar epithelium. Npj Regenerative Medicine 2023, 8: 22. PMID: 37117221, PMCID: PMC10147714, DOI: 10.1038/s41536-023-00295-2.Peer-Reviewed Original Research
2022
Lung Cell Atlases in Health and Disease
Adams T, Marlier A, Kaminski N. Lung Cell Atlases in Health and Disease. Annual Review Of Physiology 2022, 85: 47-69. PMID: 36351366, DOI: 10.1146/annurev-physiol-032922-082826.Peer-Reviewed Original ResearchConceptsCell atlasesSingle-cell profiling technologiesLung biologyProfiling technologiesCell typesCellular morphologyProgressive lung diseaseCellular measurementsHuman lung biologyGas exchangeLung diseaseComplex branching structuresRecent advancesDiseaseIndividual markersBiologyBranching structureUnprecedented levelHealthStructural changesLongitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study
Allen RJ, Oldham JM, Jenkins DA, Leavy OC, Guillen-Guio B, Melbourne CA, Ma SF, Jou J, Kim JS, Cooperative C, Fahy WA, Oballa E, Hubbard RB, Navaratnam V, Braybrooke R, Saini G, Roach KM, Tobin MD, Hirani N, Whyte MKB, Kaminski N, Zhang Y, Martinez FJ, Linderholm AL, Adegunsoye A, Strek ME, Maher TM, Molyneaux PL, Flores C, Noth I, Jenkins R, Wain LV. Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study. The Lancet Respiratory Medicine 2022, 11: 65-73. PMID: 35985358, PMCID: PMC10077113, DOI: 10.1016/s2213-2600(22)00251-x.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisLung capacityAmerican Thoracic Society/European Respiratory Society guidelinesDiagnosis of IPFEuropean Respiratory Society guidelinesPotential novel therapeutic approachHealth-National HeartLongitudinal lung functionRespiratory Society guidelinesGenetic variantsNovel therapeutic approachesIncurable lung diseaseMedical Research CouncilProgressive scarringFVC declineLung functionVital capacityBlood InstituteSociety guidelinesLung diseaseNational HeartDisease progressionTherapeutic approachesSignificant associationFrom COVID to fibrosis: lessons from single-cell analyses of the human lung
Justet A, Zhao AY, Kaminski N. From COVID to fibrosis: lessons from single-cell analyses of the human lung. Human Genomics 2022, 16: 20. PMID: 35698166, PMCID: PMC9189802, DOI: 10.1186/s40246-022-00393-0.Peer-Reviewed Original ResearchConceptsSingle-cell RNA-sequencing technologySingle-cell RNA sequencingRNA-sequencing technologyGene expression patternsMonocyte-derived macrophage populationSingle-cell analysisCell populationsLung diseaseCellular phenotypesRNA sequencingExpression patternsGene expressionAberrant repairMultiple tissuesPulmonary fibrosisMechanisms of diseaseFibrotic interstitial lung diseaseLife-threatening complicationsProgressive lung diseaseCOVID-19 pneumoniaInterstitial lung diseaseParenchymal lung diseaseAcute viral diseaseMacrophage populationsNovel cellFK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis
Preisendörfer S, Ishikawa Y, Hennen E, Winklmeier S, Schupp JC, Knüppel L, Fernandez IE, Binzenhöfer L, Flatley A, Juan-Guardela BM, Ruppert C, Guenther A, Frankenberger M, Hatz RA, Kneidinger N, Behr J, Feederle R, Schepers A, Hilgendorff A, Kaminski N, Meinl E, Bächinger HP, Eickelberg O, Staab-Weijnitz CA. FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis. Cells 2022, 11: 1341. PMID: 35456020, PMCID: PMC9027113, DOI: 10.3390/cells11081341.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPlasma cellsPulmonary fibrosisIgG antibodiesFatal chronic lung diseaseCell linesAntibody-producing plasma cellsChronic lung diseaseAdaptive immune responsesHybridoma cell linesAlveolar epithelial cell lineCell-specific antibodiesCell deathAntibody-producing hybridoma cellsAutoimmune featuresX-box-binding protein 1IPF lungsLung diseaseEpithelial cell lineImmune responseLymphatic tissueB cellsStress-mediated cell deathAntibody secretionER stress-mediated cell deathLung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis.
De Sadeleer LJ, McDonough JE, Schupp JC, Yan X, Vanstapel A, Van Herck A, Everaerts S, Geudens V, Sacreas A, Goos T, Aelbrecht C, Nawrot TS, Martens DS, Schols D, Claes S, Verschakelen JA, Verbeken EK, Ackermann M, Decottignies A, Mahieu M, Hackett TL, Hogg JC, Vanaudenaerde BM, Verleden SE, Kaminski N, Wuyts WA. Lung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2022, 205: 60-74. PMID: 34724391, PMCID: PMC8865586, DOI: 10.1164/rccm.202103-0569oc.Peer-Reviewed Original ResearchConceptsFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisHypersensitivity pneumonitisLung zonesMolecular traitsUnused donor lungsInterstitial lung diseaseLocal disease extentProgression of fibrosisSevere fibrosis groupGene co-expression network analysisCo-expression network analysisExplant lungsDonor lungsLung involvementEndothelial functionLung findingsDisease extentPulmonary fibrosisLung diseaseFibrosis groupLung microenvironmentClinical behaviorDisease progressionBAL samples
2021
Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
Bui LT, Winters NI, Chung MI, Joseph C, Gutierrez AJ, Habermann AC, Adams TS, Schupp JC, Poli S, Peter LM, Taylor CJ, Blackburn JB, Richmond BW, Nicholson AG, Rassl D, Wallace WA, Rosas IO, Jenkins RG, Kaminski N, Kropski JA, Banovich NE. Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity. Nature Communications 2021, 12: 4314. PMID: 34262047, PMCID: PMC8280215, DOI: 10.1038/s41467-021-24467-0.Peer-Reviewed Original ResearchConceptsChronic lung diseaseLung diseaseImmune responseSARS-CoV-2 entry factorsSevere coronavirus disease-19SARS-CoV-2 infectionWorse COVID-19 outcomesSARS-CoV-2 entryAdaptive immune responsesCoronavirus disease-19COVID-19 outcomesInnate immune responseInflammatory gene expression programSimilar cellular distributionPoor outcomePeripheral lungViral exposureDisease-19Inflammatory microenvironmentEntry factorsLung epitheliumLung cellsViral replicationAT2 cellsBasal differencesElevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers
Zhang Y, Tedrow J, Nouraie M, Li X, Chandra D, Bon J, Kass DJ, Fuhrman CR, Leader JK, Duncan SR, Kaminski N, Sciurba FC. Elevated plasma level of Pentraxin 3 is associated with emphysema and mortality in smokers. Thorax 2021, 76: 335-342. PMID: 33479043, PMCID: PMC8249179, DOI: 10.1136/thoraxjnl-2020-215356.Peer-Reviewed Original ResearchConceptsAirflow obstructionPlasma levelsLung tissueEmphysema severitySmoking-related lung diseaseAssociation of lungExpiratory airflow obstructionFormer tobacco smokersLevels of PTX3PTX3 gene expressionElevated plasma levelsHyaluronic acid levelsBlood of subjectsPlasma PTX3PTX3 levelsLung functionTobacco exposureClinical outcomesTobacco smokersLung diseasePentraxin 3Predictive biomarkersPTX3 expressionLower riskDisease patterns
2020
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis.
Schupp JC, Khanal S, Gomez JL, Sauler M, Adams TS, Chupp GL, Yan X, Poli S, Zhao Y, Montgomery RR, Rosas IO, Dela Cruz CS, Bruscia EM, Egan ME, Kaminski N, Britto CJ. Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2020, 202: 1419-1429. PMID: 32603604, PMCID: PMC7667912, DOI: 10.1164/rccm.202004-0991oc.Peer-Reviewed Original ResearchConceptsCF lung diseaseHealthy control subjectsImmune dysfunctionLung diseaseCystic fibrosisControl subjectsSputum cellsAbnormal chloride transportLung mononuclear phagocytesInnate immune dysfunctionDivergent clinical coursesImmune cell repertoireMonocyte-derived macrophagesCF monocytesAirway inflammationClinical courseProinflammatory featuresCell survival programInflammatory responseTissue injuryCell repertoireImmune functionTranscriptional profilesAlveolar macrophagesMononuclear phagocytesSingle-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-seqCMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis
Konikov-Rozenman J, Breuer R, Kaminski N, Wallach-Dayan SB. CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis. Biomolecules 2020, 10: 997. PMID: 32630842, PMCID: PMC7408087, DOI: 10.3390/biom10070997.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBinding SitesCASP8 and FADD-Like Apoptosis Regulating ProteinCell LineCell SurvivalDisease Models, AnimalFibroblastsGene Expression RegulationHumansHydroxamic AcidsIdiopathic Pulmonary FibrosisKu AutoantigenLungMaleMiceMice, Inbred C57BLModels, MolecularMolecular Docking SimulationProtein ConformationProtein StabilitySirtuin 1ConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisFibrotic-lung myofibroblastsProgressive lung diseaseExperimental pulmonary fibrosisFibroblast cell deathLung diseaseLung fibrosisLung sectionsVital organsFlow cytometryFibrosisMyofibroblast resistanceRegenerative capacityFLIP levelsCell survivalCell deathImmunoblotCmHSIRT1Activity inhibitionUseful strategySmall moleculesBleomycinMyofibroblasts
2019
The Human Lung Cell Atlas: A High-Resolution Reference Map of the Human Lung in Health and Disease
Schiller HB, Montoro DT, Simon LM, Rawlins EL, Meyer KB, Strunz M, Braga F, Timens W, Koppelman GH, Budinger GRS, Burgess JK, Waghray A, van den Berge M, Theis F, Regev A, Kaminski N, Rajagopal J, Teichmann S, Misharin A, Nawijn M. The Human Lung Cell Atlas: A High-Resolution Reference Map of the Human Lung in Health and Disease. American Journal Of Respiratory Cell And Molecular Biology 2019, 61: 31-41. PMID: 30995076, PMCID: PMC6604220, DOI: 10.1165/rcmb.2018-0416tr.Peer-Reviewed Original ResearchConceptsCell atlasHuman Cell Atlas consortiumCell typesCell-cell interactionsHigh-throughput techniquesFunction of geneticsLung cell typesTranscriptomic analysisDevelopmental processesIndividual cellsMolecular descriptionReference mapTissue microenvironmentDisease mechanismsCellular neighborhoodsHealthy human bodyMolecular profilePersonalized therapeutic regimensCellsLung diseaseTherapeutic regimensImmune cellsLung tissueRecent progressTissue matrix
2018
Evolving Genomics of Pulmonary Fibrosis
Ibarra G, Herazo-Maya J, Kaminski N. Evolving Genomics of Pulmonary Fibrosis. Respiratory Medicine 2018, 207-239. DOI: 10.1007/978-3-319-99975-3_9.Peer-Reviewed Original ResearchTranscript profiling approachesProfiling approachPotential drug targetsNonspecific interstitial pneumoniaIdiopathic pulmonary fibrosisFibrotic lung diseaseGenomic profiling studiesLung diseaseDrug targetsPulmonary fibrosisHypersensitivity pneumonitisKey moleculesProfiling studiesCells of patientsUnbiased viewDifferent interstitial lung diseasesInterstitial lung diseaseInterstitial pneumoniaLung fibrosisAnimal modelsTranscriptomeCellsGenomicsFibrosisDiseaseBPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation
Britto CJ, Niu N, Khanal S, Huleihel L, Herazo-Maya J, Thompson A, Sauler M, Slade MD, Sharma L, Dela Cruz CS, Kaminski N, Cohn LE. BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l321-l333. PMID: 30461288, PMCID: PMC6397348, DOI: 10.1152/ajplung.00056.2018.Peer-Reviewed Original ResearchConceptsLung inflammationAcute inflammationC motif chemokine ligand 10Lung neutrophil recruitmentRegulation of CXCL10Acute lung inflammationBronchoalveolar lavage concentrationsChemokine ligand 10Innate immune responseIFN regulatory factorIntranasal LPSLavage concentrationsLung recruitmentNeutrophil recruitmentWT miceImmune effectsLung diseasePMN recruitmentInflammatory responseLPS treatmentLung tissueInflammatory signalsImmune responseImmunomodulatory propertiesInflammationGene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis
McDonough JE, Kaminski N, Thienpont B, Hogg JC, Vanaudenaerde BM, Wuyts WA. Gene correlation network analysis to identify regulatory factors in idiopathic pulmonary fibrosis. Thorax 2018, 74: 132. PMID: 30366970, PMCID: PMC6467239, DOI: 10.1136/thoraxjnl-2018-211929.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung functionPulmonary fibrosisExtensive pathological changesSevere lung diseaseLung Tissue Research ConsortiumCorrelation network analysisIPF cohortIPF groupLung diseaseControl subjectsUpregulated modulesT cellsImmune responsePathological changesLeucocyte activationB cellsClinical relevanceSurfactant metabolismDisease pathologyInterferon responseFibrosisBlood vesselsPathological processesGene correlation network analysisCharacteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease – analysis of institutional and population data
Yoon JH, Nouraie M, Chen X, Zou RH, Sellares J, Veraldi KL, Chiarchiaro J, Lindell K, Wilson DO, Kaminski N, Burns T, Trejo Bittar H, Yousem S, Gibson K, Kass DJ. Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease – analysis of institutional and population data. Respiratory Research 2018, 19: 195. PMID: 30285867, PMCID: PMC6171146, DOI: 10.1186/s12931-018-0899-4.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisSingle lung transplantInterstitial lung diseaseLung cancerIPF patientsPulmonary fibrosisIPF ILDNon-IPF ILD patientsLung Cancer RegistrySquamous cell histologySquamous cell carcinomaStandard incidence ratioBackgroundLung cancerCenter registryILD patientsLung transplantCell histologyClinical characteristicsInterstitial lungCancer RegistryIncidence ratiosWorse prognosisLower lobeCell carcinomaLung disease