2021
Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma
Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Respiratory Research 2021, 22: 122. PMID: 33902571, PMCID: PMC8074196, DOI: 10.1186/s12931-021-01709-9.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsSevere asthmaEffector T cellsBlood mononuclear cellsT cellsHealthy controlsPoly IDendritic cellsMononuclear cellsUnstimulated peripheral blood mononuclear cellsInterferon responseTLR3 agonist poly IImpaired interferon responseMain cell subsetsNatural killer cellsPro-inflammatory profilePro-inflammatory pathwaysC stimulationCyTOF profilingHigh CD8Cell typesEffector cellsKiller cellsCell subsetsMain cell typesMicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease
Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan IS, Li CX, Sköld C, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra RS, Wheelock ÅM, Gomez JL, Kaminski N, Lee PJ, Sauler M. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease. JCI Insight 2021, 6: e134218. PMID: 33290275, PMCID: PMC7934877, DOI: 10.1172/jci.insight.134218.Peer-Reviewed Original ResearchConceptsCellular stress responseStress responseHomology-directed DNA repairDNA damage responseProtein BRCA1Damage responseCellular stressDNA repairProtein BimCOPD lung tissueLung epithelial cellsCellular responsesExpression arraysEpithelial cell apoptosisDNA damageChronic obstructive pulmonary diseaseBRCA1 expressionCell apoptosisApoptosisEpithelial cellsCritical mechanismMicroRNAsRegulatorObstructive pulmonary diseaseIncreases Susceptibility
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 phagocytesApproaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients
Spakowicz D, Lou S, Barron B, Gomez JL, Li T, Liu Q, Grant N, Yan X, Hoyd R, Weinstock G, Chupp GL, Gerstein M. Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients. Genome Biology 2020, 21: 150. PMID: 32571363, PMCID: PMC7310008, DOI: 10.1186/s13059-020-02033-z.Peer-Reviewed Original ResearchA Network of Sputum MicroRNAs is Associated with Neutrophilic Airway Inflammation in Asthma
Gomez JL, Chen A, Diaz MP, Zirn N, Gupta A, Britto C, Sauler M, Yan X, Stewart E, Santerian K, Grant N, Liu Q, Fry R, Rager J, Cohn L, Alexis N, Chupp GL. A Network of Sputum MicroRNAs is Associated with Neutrophilic Airway Inflammation in Asthma. American Journal Of Respiratory And Critical Care Medicine 2020, 0: 51-64. PMID: 32255668, PMCID: PMC7328332, DOI: 10.1164/rccm.201912-2360oc.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum stressAirway inflammationNeutrophil countClinical featuresT-helper cell type 17Neutrophilic airway inflammationReticulum stressSputum of subjectsLung function impairmentHistory of hospitalizationNumber of neutrophilsPeripheral blood neutrophilsSputum of patientsMicroRNA expressionAsthma severityTh17 pathwayFunction impairmentAirway samplesMicroRNA networkBlood neutrophilsOzone exposureAsthmaSputumCellular sourceClinical phenotype
2018
The DNA repair transcriptome in severe COPD
Sauler M, Lamontagne M, Finnemore E, Herazo-Maya JD, Tedrow J, Zhang X, Morneau JE, Sciurba F, Timens W, Paré PD, Lee PJ, Kaminski N, Bossé Y, Gomez JL. The DNA repair transcriptome in severe COPD. European Respiratory Journal 2018, 52: 1701994. PMID: 30190272, PMCID: PMC6422831, DOI: 10.1183/13993003.01994-2017.Peer-Reviewed Original ResearchConceptsDNA damage toleranceDNA repairInadequate DNA repairSevere chronic obstructive pulmonary diseaseChronic obstructive pulmonary diseaseRepair pathwaysGene correlation network analysisIntegrative genomics approachNucleotide excision repair pathwayDNA repair pathwaysGene Set Enrichment AnalysisExcision repair pathwayGlobal transcriptomic profilesDNA repair genesDNA repair responseCorrelation network analysisCOPD severityGenomic approachesLung tissue transcriptomeTranscriptomic differencesTranscriptomic changesTranscriptomic patternsRNA sequencingTissue transcriptomesTranscriptomic profiles
2017
Characterisation of asthma subgroups associated with circulating YKL-40 levels
Gomez JL, Yan X, Holm CT, Grant N, Liu Q, Cohn L, Nezgovorova V, Meyers DA, Bleecker ER, Crisafi GM, Jarjour NN, Rogers L, Reibman J, Chupp GL. Characterisation of asthma subgroups associated with circulating YKL-40 levels. European Respiratory Journal 2017, 50: 1700800. PMID: 29025889, PMCID: PMC5967238, DOI: 10.1183/13993003.00800-2017.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge of OnsetAirway ObstructionAsthmaChitinase-3-Like Protein 1Cluster AnalysisCross-Sectional StudiesDisease ProgressionFemaleGene Expression ProfilingHumansInflammationMaleMiddle AgedReproducibility of ResultsRespiratory SystemSeverity of Illness IndexSputumStatistics as TopicSymptom Flare UpConceptsSerum YKL-40 levelsYKL-40 levelsHigher serum YKL-40 levelsAirflow obstructionAsthma phenotypesElevated serum YKL-40 levelsSevere Asthma Research ProgramClinical asthma phenotypesExacerbation-prone asthmaIrreversible airway obstructionSevere airflow obstructionFrequent exacerbationsSevere exacerbationsAirway inflammationAirway obstructionAsthma exacerbationsAirway diseaseAsthma patientsAsthma severitySerum levelsInflammatory pathwaysAsthma subgroupsAdult onsetIdentification of individualsUnsupervised cluster analysis
2015
Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma
Yan X, Chu JH, Gomez J, Koenigs M, Holm C, He X, Perez MF, Zhao H, Mane S, Martinez FD, Ober C, Nicolae DL, Barnes KC, London SJ, Gilliland F, Weiss ST, Raby BA, Cohn L, Chupp GL. Noninvasive Analysis of the Sputum Transcriptome Discriminates Clinical Phenotypes of Asthma. American Journal Of Respiratory And Critical Care Medicine 2015, 191: 1116-1125. PMID: 25763605, PMCID: PMC4451618, DOI: 10.1164/rccm.201408-1440oc.Peer-Reviewed Original ResearchConceptsHistory of intubationNitric oxide levelsOxide levelsClinical phenotypeMost subjectsHigher bronchodilator responseNormal lung functionBlood of patientsCohort of childrenLogistic regression analysisSputum gene expressionBlood of childrenAirway transcriptomeMilder asthmaPathophysiologic heterogeneityPrebronchodilator FEV1Steroid requirementsLung functionBronchodilator responseGene expressionPhenotype of diseaseAsthmaBlood samplesGene signatureIntubationGenetic variation in chitinase 3-like 1 (CHI3L1) contributes to asthma severity and airway expression of YKL-40
Gomez JL, Crisafi GM, Holm CT, Meyers DA, Hawkins GA, Bleecker ER, Jarjour N, Investigators S, Cohn L, Chupp GL. Genetic variation in chitinase 3-like 1 (CHI3L1) contributes to asthma severity and airway expression of YKL-40. Journal Of Allergy And Clinical Immunology 2015, 136: 51-58.e10. PMID: 25592985, PMCID: PMC4494869, DOI: 10.1016/j.jaci.2014.11.027.Peer-Reviewed Original ResearchConceptsYKL-40 levelsYKL-40 expressionSerum YKL-40 levelsAsthma severityYKL-40Airway expressionAirway diseaseLung functionSingle nucleotide polymorphismsChitinase 3Severe Asthma Research ProgramHigh YKL-40 expressionOnly single nucleotide polymorphismRisk allele APostbronchodilator FEV1Airflow obstructionFEV1 percentSevere asthmaAsthmatic subjectsAsthma prevalenceHaplotype analysisGene polymorphismsG alleleCHI3L1 geneAsthma