2022
Lung 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
Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19
2020
Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways
Li X, Christenson SA, Modena B, Li H, Busse WW, Castro M, Denlinger LC, Erzurum SC, Fahy JV, Gaston B, Hastie AT, Israel E, Jarjour NN, Levy BD, Moore WC, Woodruff PG, Kaminski N, Wenzel SE, Bleecker ER, Meyers DA, Program N. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. Journal Of Allergy And Clinical Immunology 2020, 147: 894-909. PMID: 32795586, PMCID: PMC7876167, DOI: 10.1016/j.jaci.2020.07.030.Peer-Reviewed Original ResearchConceptsExpression quantitative trait loci (eQTL) analysisQuantitative trait locus (QTL) analysisSingle nucleotide polymorphismsGasdermin BMultiple single nucleotide polymorphismsFunctional genesExpression levelsLocus analysisAntiviral pathwaysGenes/single-nucleotide polymorphismsWhole genome sequencesGene expression dataEpithelial cellsImmune system pathwaysHigh expression levelsHuman bronchial epithelial cellsIFN regulatory factorGPI attachmentGSDMB expressionAsthma susceptibilityGenetic analysisGene expressionPathway analysisBronchial epithelial cellsRegulatory factorsExpression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype
Camiolo M, Gauthier M, Kaminski N, Ray A, Wenzel SE. Expression of SARS-CoV-2 receptor ACE2 and coincident host response signature varies by asthma inflammatory phenotype. Journal Of Allergy And Clinical Immunology 2020, 146: 315-324.e7. PMID: 32531372, PMCID: PMC7283064, DOI: 10.1016/j.jaci.2020.05.051.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAngiotensin-Converting Enzyme 2AsthmaBetacoronavirusBiomarkersBronchiBronchoalveolar Lavage FluidCohort StudiesCoronavirus InfectionsCOVID-19EosinophilsFemaleGene Expression ProfilingHumansInterferon Type IInterferon-gammaMaleMiddle AgedPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein Interaction MappingReceptors, VirusRisk FactorsSARS-CoV-2Severity of Illness IndexT-LymphocytesTranscriptomeUnited StatesConceptsCoronavirus disease 2019Severe coronavirus disease 2019Subset of patientsDisease 2019Risk factorsBronchial epitheliumAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSevere acute respiratory syndrome coronavirus 2Syndrome coronavirus 2 infectionType 2 inflammatory biomarkersAcute respiratory syndrome coronavirus 2Receptor ACE2SARS-CoV-2 receptor ACE2Respiratory syndrome coronavirus 2Asthma inflammatory phenotypesLarge asthma cohortsLower peripheral bloodT cell-activating factorCoronavirus 2 infectionEnzyme 2 (ACE2) expressionHistory of hypertensionDiagnosis of asthmaBronchoalveolar lavage lymphocytesT cell recruitment
2019
BAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications
Weathington N, O’Brien M, Radder J, Whisenant TC, Bleecker ER, Busse WW, Erzurum SC, Gaston B, Hastie A, Jarjour N, Meyers D, Milosevic J, Moore W, Tedrow J, Trudeau J, Wong H, Wu W, Kaminski N, Wenzel S, Modena B. BAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications. American Journal Of Respiratory And Critical Care Medicine 2019, 200: 837-856. PMID: 31161938, PMCID: PMC6812436, DOI: 10.1164/rccm.201811-2221oc.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic beta-AgonistsAdultAsthmaBronchoalveolar Lavage FluidCase-Control StudiesCyclic AMPEosinophilsEpithelial CellsFemaleGene ExpressionHumansIn Vitro TechniquesLymphocytesMacrophages, AlveolarMaleNeutrophilsSequence Analysis, RNASeverity of Illness IndexSignal TransductionTHP-1 CellsConceptsCell gene expressionGene expressionAirway epithelial cell gene expressionEpithelial cell gene expressionGlobal gene expressionCellular gene expressionCell expression profilesAsthma susceptibility lociProtein levelsSystem-wide analysisExpression networksImportant disease mechanismCoexpression networkCellular milieuExpression changesExpression profilesSusceptibility lociCellular modelDisease mechanismsBiomolecular mechanismsNew targetsRobust upregulationSample traitsGenesExpression
2017
Extreme Trait Whole-Genome Sequencing Identifies PTPRO as a Novel Candidate Gene in Emphysema with Severe Airflow Obstruction
Radder JE, Zhang Y, Gregory AD, Yu S, Kelly NJ, Leader JK, Kaminski N, Sciurba FC, Shapiro SD. Extreme Trait Whole-Genome Sequencing Identifies PTPRO as a Novel Candidate Gene in Emphysema with Severe Airflow Obstruction. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 159-171. PMID: 28199135, PMCID: PMC5519967, DOI: 10.1164/rccm.201606-1147oc.Peer-Reviewed Original ResearchConceptsNovel candidate genesCandidate genesSuggestive associationSuggestive candidate genesRare genetic variationRare variationRegion-based testsGene-based testsSingle-variant testsRare nonsynonymous variantsWhole-genome sequencingRare variantsWhole genome sequencing resultsGenomic regionsGenetic variationGenetic association studiesDisease heritabilityCellular pathwaysAssociation studiesExtreme phenotypesPTPRONonsynonymous variantsSequencing resultsGenesDisease susceptibility
2016
Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease
Modena BD, Bleecker ER, Busse WW, Erzurum SC, Gaston BM, Jarjour NN, Meyers DA, Milosevic J, Tedrow JR, Wu W, Kaminski N, Wenzel SE. Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease. American Journal Of Respiratory And Critical Care Medicine 2016, 195: 1449-1463. PMID: 27984699, PMCID: PMC5470748, DOI: 10.1164/rccm.201607-1407oc.Peer-Reviewed Original ResearchConceptsWeighted gene coexpression network analysisGene coexpression network analysisCoexpression network analysisGene expressionBiological processesAirway epithelial cell gene expressionEpithelial cell gene expressionNetwork of genesGene expression networksGene network modulesAsthma susceptibility lociT2 gene expressionCell gene expressionGene expression studiesNeuronal functionEpithelial growthMultiple molecular mechanismsExpression networksT2 genesGene networksUnderlying biological processesHub genesExpression studiesBiological insightsNetwork analysisExpression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort
Li X, Hawkins GA, Moore WC, Hastie AT, Ampleford EJ, Milosevic J, Li H, Busse WW, Erzurum SC, Kaminski N, Wenzel SE, Bleecker ER, Meyers DA. Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort. Journal Of Asthma 2016, 53: 775-782. PMID: 27050946, PMCID: PMC5137190, DOI: 10.3109/02770903.2016.1158268.Peer-Reviewed Original Research
2014
Wnt Coreceptor Lrp5 Is a Driver of Idiopathic Pulmonary Fibrosis
Lam AP, Herazo-Maya JD, Sennello JA, Flozak AS, Russell S, Mutlu GM, Budinger GR, DasGupta R, Varga J, Kaminski N, Gottardi CJ. Wnt Coreceptor Lrp5 Is a Driver of Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2014, 190: 185-195. PMID: 24921217, PMCID: PMC4226053, DOI: 10.1164/rccm.201401-0079oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsBeta CateninBiomarkersDisease ProgressionFemaleHumansIdiopathic Pulmonary FibrosisLeukocytes, MononuclearLow Density Lipoprotein Receptor-Related Protein-5Low Density Lipoprotein Receptor-Related Protein-6MaleMiceMice, KnockoutMiddle AgedProspective StudiesSeverity of Illness IndexSignal TransductionTransforming Growth Factor betaWnt ProteinsConceptsIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsBlood mononuclear cellsLung fibrosisPulmonary fibrosisDisease progressionMononuclear cellsDisease severityNull miceAlveolar type 2 cellsTGF-β productionWild-type miceActivation of TGFType 2 cellsWnt pathway inhibitorsWnt/β-catenin signalingWnt coreceptors LRP5Role of LRP5Bone marrow cellsLrp5 lossΒ-catenin signalingPatient selectionSmall molecular inhibitorsAdditional cohortFibrosisThe Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis
Huang LS, Mathew B, Li H, Zhao Y, Ma SF, Noth I, Reddy SP, Harijith A, Usatyuk PV, Berdyshev EV, Kaminski N, Zhou T, Zhang W, Zhang Y, Rehman J, Kotha SR, Gurney TO, Parinandi NL, Lussier YA, Garcia JG, Natarajan V. The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2014, 189: 1402-1415. PMID: 24779708, PMCID: PMC4098083, DOI: 10.1164/rccm.201310-1917oc.Peer-Reviewed Original ResearchMeSH Keywords1-Acylglycerol-3-Phosphate O-AcyltransferaseAcyltransferasesAnimalsBiomarkersCardiolipinsCohort StudiesDisease Models, AnimalHumansIdiopathic Pulmonary FibrosisIn Situ HybridizationLeukocytes, MononuclearMiceMitochondriaPredictive Value of TestsPulmonary FibrosisRNA, MessengerSensitivity and SpecificitySeverity of Illness IndexConceptsPeripheral blood mononuclear cellsIdiopathic pulmonary fibrosisPulmonary fibrosisMurine modelAlveolar epithelial cellsOverall survivalReactive oxygen species generationLysocardiolipin acyltransferaseOxygen species generationCarbon monoxide diffusion capacityRadiation-induced pulmonary fibrosisPulmonary function outcomesEpithelial cellsBlood mononuclear cellsPreclinical murine modelsNovel therapeutic approachesSpecies generationBleomycin challengeLung inflammationLung protectionPulmonary functionFunction outcomesLung fibrosisMononuclear cellsFibrotic lungsC-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis
Vuga LJ, Tedrow JR, Pandit KV, Tan J, Kass DJ, Xue J, Chandra D, Leader JK, Gibson KF, Kaminski N, Sciurba FC, Duncan SR. C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2014, 189: 966-974. PMID: 24628285, PMCID: PMC4098096, DOI: 10.1164/rccm.201309-1592oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBiomarkersCase-Control StudiesChemokine CXCL13Disease ProgressionEnzyme-Linked Immunosorbent AssayFemaleHumansIdiopathic Pulmonary FibrosisImmunohistochemistryMaleMiddle AgedOligonucleotide Array Sequence AnalysisPredictive Value of TestsPrognosisPulmonary Disease, Chronic ObstructiveRisk FactorsSensitivity and SpecificitySeverity of Illness IndexConceptsChronic obstructive pulmonary diseaseC motif chemokine 13IPF lungsPrognostic biomarkerB cellsIdiopathic pulmonary fibrosis (IPF) pathogenesisB cell-targeted therapiesAntibody-mediated syndromeDysregulated B cellsPulmonary fibrosis pathogenesisPulmonary artery hypertensionObstructive pulmonary diseaseIdiopathic pulmonary fibrosisSix-month survivalB-cell traffickingAcute exacerbationArtery hypertensionCXCL13 mRNAPlasma CXCL13IPF pathogenesisRespiratory failureLung injuryCXCL13 concentrationsPulmonary diseaseRadiographic emphysemaAn airway epithelial iNOS–DUOX2–thyroid peroxidase metabolome drives Th1/Th2 nitrative stress in human severe asthma
Voraphani N, Gladwin MT, Contreras AU, Kaminski N, Tedrow JR, Milosevic J, Bleecker ER, Meyers DA, Ray A, Ray P, Erzurum SC, Busse WW, Zhao J, Trudeau JB, Wenzel SE. An airway epithelial iNOS–DUOX2–thyroid peroxidase metabolome drives Th1/Th2 nitrative stress in human severe asthma. Mucosal Immunology 2014, 7: 1175-1185. PMID: 24518246, PMCID: PMC4130801, DOI: 10.1038/mi.2014.6.Peer-Reviewed Original ResearchConceptsInducible nitric oxide synthaseHuman airway epithelial cellsDual oxidase 2Severe asthmaNitrative stressThyroid peroxidaseIL-13Ex vivoSevere refractory asthmaNitric oxide synthaseTh2 cytokine expressionAirway epithelial cellsRefractory asthmaLower interleukinHigher interferonCytokine expressionOxide synthaseOxidase 2AsthmaIFNEpithelial cellsEpithelial cell systemSuperoxide dismutaseRNA knockdownEndogenous peroxidase
2013
Oral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis: A Randomized, Single-Masked, Placebo-Controlled Study
Drake WP, Oswald-Richter K, Richmond BW, Isom J, Burke VE, Algood H, Braun N, Taylor T, Pandit KV, Aboud C, Yu C, Kaminski N, Boyd AS, King LE. Oral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis: A Randomized, Single-Masked, Placebo-Controlled Study. JAMA Dermatology 2013, 149: 1040-1049. PMID: 23863960, PMCID: PMC3927541, DOI: 10.1001/jamadermatol.2013.4646.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAnti-Bacterial AgentsAzithromycinCD4-Positive T-LymphocytesChronic DiseaseDrug Therapy, CombinationEthambutolFemaleFollow-Up StudiesHumansLevofloxacinMaleMiddle AgedOfloxacinRifampinSarcoidosisSeverity of Illness IndexSingle-Blind MethodSkin DiseasesTranscriptomeTreatment OutcomeYoung AdultConceptsChronic cutaneous sarcoidosisCutaneous sarcoidosis lesionsAntimycobacterial therapyLesion diameterCutaneous sarcoidosisSarcoidosis lesionsDisease severityPlacebo-controlled studyPlacebo-treated groupCompletion of therapyT cell functionChronic granulomatous diseaseT cell receptor stimulationSignificant reductionConcomitant levofloxacinPlacebo regimenRifampin regimenSingle-MaskedPlacebo groupTreat analysisDermatology centersTherapeutic optionsGranulomatous diseaseT cellsLesion severity
2005
Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors
Segman RH, Shefi N, Goltser-Dubner T, Friedman N, Kaminski N, Shalev AY. Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors. Molecular Psychiatry 2005, 10: 500-513. PMID: 15685253, DOI: 10.1038/sj.mp.4001636.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PsychologicalAdolescentAdultFollow-Up StudiesGene Expression ProfilingGenetic MarkersHumansLeukocytes, MononuclearLife Change EventsMiddle AgedOligonucleotide Array Sequence AnalysisPredictive Value of TestsSeverity of Illness IndexStress Disorders, Post-TraumaticStress, PsychologicalSurvivorsConceptsGene expression signaturesPeripheral blood mononuclear cell gene expressionExpression signaturesTrauma survivorsPeripheral blood mononuclear cell gene expression profilesTime pointsDSM-IV diagnostic criteriaKey clinical featuresPost-traumatic stress disorder symptomsPost-traumatic stress disorderCell gene expression profilesClinical featuresOutcome predictorsEmergency roomPTSD symptom clustersDevelopment of PTSDPathogenetic implicationsDiagnostic criteriaChronic PTSDDiagnostic utilityEarly symptomsMental disordersNeuropsychiatric disordersSymptom clustersPTSD criteria