2023
Sputum alarmins delineate distinct T2 cytokine pathways and unique subtypes of patients with asthma
Gautam S, Chu J, Cohen A, Kaur R, Lee S, Wilson G, Liu Q, Gomez J, Rajaveen H, Yan X, Cohn L, Clark B, Chupp G. Sputum alarmins delineate distinct T2 cytokine pathways and unique subtypes of patients with asthma. Allergy 2023, 78: 3274-3277. PMID: 37874609, PMCID: PMC10842366, DOI: 10.1111/all.15915.Peer-Reviewed Original ResearchDeep learning prediction of hospital readmissions for asthma and COPD
Lopez K, Li H, Lipkin-Moore Z, Kay S, Rajeevan H, Davis J, Wilson F, Rochester C, Gomez J. Deep learning prediction of hospital readmissions for asthma and COPD. Respiratory Research 2023, 24: 311. PMID: 38093373, PMCID: PMC10720134, DOI: 10.1186/s12931-023-02628-7.Peer-Reviewed Original Research
2022
CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging.
Cui H, Xie N, Banerjee S, Dey T, Liu RM, Antony VB, Sanders YY, Adams TS, Gomez JL, Thannickal VJ, Kaminski N, Liu G. CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 459-475. PMID: 35687485, DOI: 10.1164/rccm.202109-2151oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung fibrosisCD38 expressionAlveolar epithelial cell injuryEpithelial cell injuryEffective therapeutic strategyHuman lung parenchymaIPF lungsLung functionPulmonary fibrosisDisease progressionFibrotic lungsReal-time PCRYoung miceLung parenchymaOld miceCell injuryTherapeutic strategiesFibrosisPharmacological inactivationCD38Single-cell RNA sequencingFlow cytometryWestern blottingOld animalsCharacterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
2021
Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis
Kumar A, Elko E, Bruno SR, Mark ZF, Chamberlain N, Mihavics BK, Chandrasekaran R, Walzer J, Ruban M, Gold C, Lam YW, Ghandikota S, Jegga AG, Gomez JL, Janssen-Heininger YM, Anathy V. Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis. Thorax 2021, 77: 669-678. PMID: 34400514, PMCID: PMC8847543, DOI: 10.1136/thoraxjnl-2021-216882.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisProtein disulfide isomerase A3Lung fibrosisPulmonary fibrosisClub cellsFibrosis-related proteinsMechanism of actionControl patientsLung functionBleomycin modelLung parenchymaFibrosisTherapeutic potentialMiceOsteopontin productionSpecific deletionPatientsProtein signaturesInhibitionResearch ConsortiumPathologyCellsSPP1Human transcriptome datasetsMajor interactorsGenes, environment, and developmental timing: New insights from translational approaches to understand early origins of respiratory diseases
Gutierrez MJ, Perez GF, Gomez JL, Rodriguez‐Martinez C, Castro‐Rodriguez J, Nino G. Genes, environment, and developmental timing: New insights from translational approaches to understand early origins of respiratory diseases. Pediatric Pulmonology 2021, 56: 3157-3165. PMID: 34388306, PMCID: PMC8858026, DOI: 10.1002/ppul.25598.Peer-Reviewed Original ResearchConceptsDevelopmental timingHistone modificationsPotential molecular mechanismsEpigenetic paradigmEpigenetic reprogrammingGenetic reprogrammingDevelopmental programDNA methylationMolecular mechanismsMolecular programmingReprogrammingEarly originsGenesLatest insightsNew insightsOmicsMethylationMicroRNAsHomeostasisLife-long consequencesInsightsTranslational approachRespiratory mucosaRespiratory diseaseCurrent evidenceSPLUNC1: a novel marker of cystic fibrosis exacerbations
Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. SPLUNC1: a novel marker of cystic fibrosis exacerbations. European Respiratory Journal 2021, 58: 2000507. PMID: 33958427, PMCID: PMC8571118, DOI: 10.1183/13993003.00507-2020.Peer-Reviewed Original ResearchConceptsAcute pulmonary exacerbationsSPLUNC1 levelsCystic fibrosisClinical outcomesCF participantsLong-term disease controlNasal epithelium clone 1Cystic fibrosis exacerbationsHigher AE riskLung function declineCytokines interleukin-1βTumor necrosis factorAE riskClinical worseningPulmonary exacerbationsStable patientsLung functionAirway clearanceFunction declineSputum collectionAcute inflammationInflammatory cytokinesMicrobiology findingsCF careClinical managementSingle-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 typesIFN Stimulates ACE2 Expression in Pediatric Airway Epithelial Cells
Salka K, Abutaleb K, Chorvinsky E, Thiruvengadam G, Arroyo M, Gomez JL, Gutierrez MJ, Pillai DK, Jaiswal JK, Nino G. IFN Stimulates ACE2 Expression in Pediatric Airway Epithelial Cells. American Journal Of Respiratory Cell And Molecular Biology 2021, 64: 515-518. PMID: 33544656, PMCID: PMC8008803, DOI: 10.1165/rcmb.2020-0352le.Peer-Reviewed Original ResearchMicroRNA 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 phagocytesBioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease
Ryu C, Walia A, Ortiz V, Perry C, Woo S, Reeves BC, Sun H, Winkler J, Kanyo JE, Wang W, Vukmirovic M, Ristic N, Stratton EA, Meena SR, Minasyan M, Kurbanov D, Liu X, Lam TT, Farina G, Gomez JL, Gulati M, Herzog EL. Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease. Arthritis & Rheumatology 2020, 72: 1905-1915. PMID: 32602227, PMCID: PMC8081728, DOI: 10.1002/art.41418.Peer-Reviewed Original ResearchConceptsCGAS/STING activationExtracellular vesiclesMitochondrial DNAPattern recognition receptorsCyclic GMP-AMP synthase/stimulatorHuman lung fibroblastsSSc-ILD cohortsInterstitial lung diseaseMT-ATP6 geneΑ-SMA expressionI interferonSSc-ILDScleroderma-Associated Interstitial Lung DiseaseSynthetic CpG DNATLR-9Clinical outcomesLung diseaseSTING activationInterleukin-6Enzyme-linked immunosorbent assay-based methodProteomic profilesMulticellular originSystemic sclerosis-associated interstitial lung diseaseImmune pattern recognition receptorsExtracellular mtDNAApproaches 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 phenotypeAn endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis
Korde A, Ahangari F, Haslip M, Zhang X, Liu Q, Cohn L, Gomez JL, Chupp G, Pober JS, Gonzalez A, Takyar SS. An endothelial microRNA-1–regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis. Journal Of Allergy And Clinical Immunology 2020, 145: 550-562. PMID: 32035607, PMCID: PMC8440091, DOI: 10.1016/j.jaci.2019.10.031.Peer-Reviewed Original ResearchConceptsMiR-1 levelsAllergic airway inflammationChronic rhinosinusitisP-selectin levelsEndothelium-specific overexpressionLung endotheliumAirway eosinophiliaAirway inflammationAsthmatic patientsTissue eosinophiliaMiR-1House dust mite modelEndothelial cellsThymic stromal lymphopoietinNumber of hospitalizationsHuman lung endotheliumIL-13 stimulationCRS cohortQuantitative RT-PCRSputum eosinophiliaAirway obstructionAsthma modelAsthma phenotypesLentiviral vector deliveryMurine model
2019
Epigenetics in Asthma
Gomez JL. Epigenetics in Asthma. Current Allergy And Asthma Reports 2019, 19: 56. PMID: 31776749, PMCID: PMC6986424, DOI: 10.1007/s11882-019-0886-y.BooksConceptsChildhood asthmaCommon chronic respiratory diseasePurpose of ReviewAsthmaChronic respiratory diseasesUnderlying pathophysiological processesHuman asthmaAllergic inflammationAsthma endotypesHealthcare utilizationAsthma pathogenesisEpigenetic mechanismsImmune cellsRespiratory diseaseAsthmaHuman studiesPathophysiological processesSummaryThis reviewSpecific methylation signaturesNovel findingsMethylation signaturesCurrent literatureAdditional researchFuture studiesRegulatory roleEndotypes
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 profilesCharacterization of Sex-Based Dna Methylation Signatures in the Airways During Early Life
Nino C, Perez G, Isaza N, Gutierrez M, Gomez J, Nino G. Characterization of Sex-Based Dna Methylation Signatures in the Airways During Early Life. Scientific Reports 2018, 8: 5526. PMID: 29615635, PMCID: PMC5882800, DOI: 10.1038/s41598-018-23063-5.Peer-Reviewed Original ResearchConceptsX-linked genesDNA methylation signaturesDifferential methylationMethylation signaturesGenome-wide DNA methylationProtein coding transcriptsX chromosome dosageX-chromosome methylationEpigenomic marksMethylation patternsX chromosomeDNA methylationCpG sitesGenomic signaturesX-inactivationGenetic componentCoding transcriptsGenesMethylation signalsAirways of infantsInfants aged 1Independent populationsRespiratory phenotypeAirway expressionIndividual's sexImpaired type I interferon regulation in the blood transcriptome of recurrent asthma exacerbations
Gomez JL, Diaz MP, Nino G, Britto CJ. Impaired type I interferon regulation in the blood transcriptome of recurrent asthma exacerbations. BMC Medical Genomics 2018, 11: 21. PMID: 29486764, PMCID: PMC5830339, DOI: 10.1186/s12920-018-0340-3.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsAsthma exacerbationsInterferon-stimulated genesRespiratory infectionsIL-15Vivo cohortToll-like receptor 2STAT1 responseRecurrent asthma exacerbationsAcute asthma exacerbationPro-inflammatory moleculesType I interferon regulationBlood mononuclear cellsPro-inflammatory signatureTranscriptomic signaturesType I interferonFold changeAdult asthmaAcute phaseMononuclear cellsImmunologic genesExacerbationIndependent cohortReceptor 2I interferon
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