2024
Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.
Unterman A, Zhao A, Neumark N, Schupp J, Ahangari F, Cosme C, Sharma P, Flint J, Stein Y, Ryu C, Ishikawa G, Sumida T, Gomez J, Herazo-Maya J, Dela Cruz C, Herzog E, Kaminski N. Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 484-496. PMID: 38717443, PMCID: PMC11351796, DOI: 10.1164/rccm.202306-0979oc.Peer-Reviewed Original ResearchStable idiopathic pulmonary fibrosisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsProgressive idiopathic pulmonary fibrosisPeripheral immune systemT cellsPulmonary fibrosisCohort of IPF patientsAssociated with decreased survivalIdiopathic pulmonary fibrosis patientsPeripheral blood mononuclear cell samplesPeripheral blood cell populationsImmune systemFraction of TregsRegulatory T cellsBlood mononuclear cellsBlood cell populationsFlow cytometry analysisImmune aberrationsIPF patientsTregsMononuclear cellsSingle-cell RNA sequencingLung homogenatesMonocyte chemoattractantCFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling
Yin H, Kockar Kizilirmak T, Li N, Adams T, Sauler M, Gomez J, Britto-Leon C. CFTR Modulators Reprogram Sex-Specific Airway Neutrophil Signaling. 2024, a7454-a7454. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a7454.Peer-Reviewed Original Research
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 ResearchShared genetic architecture of blood eosinophil counts and asthma in UK Biobank
Li B, Wang Y, Wang Z, Li X, Kay S, Chupp G, Zhao H, Gomez J. Shared genetic architecture of blood eosinophil counts and asthma in UK Biobank. ERJ Open Research 2023, 9: 00291-2023. PMID: 37650091, PMCID: PMC10463033, DOI: 10.1183/23120541.00291-2023.Peer-Reviewed Original ResearchGenome-wide association studiesGenetic architectureGenetic correlation analysisUK BiobankGWAS resultsTranscription factorsInterleukin-4 SignalingBlood eosinophil countsAssociation studiesDoctor-diagnosed asthmaSignificant variantsEosinophil countEuropean ancestryTraitsPathwayGenetic linkType 2 immune responsesType 2 inflammationSignalingCritical associationImmune responseHeterogeneous diseaseTAGCSevere asthmaTherapeutic interventionsMortality Differences Among Patients With Airway Disease Hospitalized With COVID-19
Liu Y, Rajeevan H, Simonov M, Wilson F, Desir G, Vinetz J, Yan X, Wang Z, Clark B, Possick J, Price C, Lutchmansingh D, Gomez J, Cohn L, Gautam S, Chupp G. Mortality Differences Among Patients With Airway Disease Hospitalized With COVID-19. 2023, a6297-a6297. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a6297.Peer-Reviewed Original ResearchMachine Learning Prediction of Severe Asthma and COPD Hospital Readmission
Li H, Lopez K, Lipkin-Moore Z, Kay S, Rajeevan H, Davis J, Wilson F, Rochester C, Gomez J. Machine Learning Prediction of Severe Asthma and COPD Hospital Readmission. 2023, a4831-a4831. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a4831.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 managementLung Compliance Clusters of COVID-ARDS Identify Distinct Subgroups with Increased Mortality
Alapaty S, Siner J, Sauler M, Baldassarri S, Davis J, Gomez J. Lung Compliance Clusters of COVID-ARDS Identify Distinct Subgroups with Increased Mortality. 2021, a2492-a2492. DOI: 10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a2492.Peer-Reviewed Original ResearchAblation or Inhibition of Protein Disulfide Isomerase A3 (PDIA3) in Club Cells Attenuates Osteopontin (SPP1) Production and Lung Fibrosis
Kumar A, Elko E, Bruno S, Mark Z, Chamberlain N, Korwin-Mihavics B, Chandrasekaran R, walzer J, Ruban M, Gold C, Lam Y, Gomez J, Janssen-Heininger Y, Anathy V. Ablation or Inhibition of Protein Disulfide Isomerase A3 (PDIA3) in Club Cells Attenuates Osteopontin (SPP1) Production and Lung Fibrosis. 2021, a4241-a4241. DOI: 10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a4241.Peer-Reviewed Original ResearchSingle-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 SusceptibilityMacrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. Journal Of Clinical Investigation 2021, 131: e136542. PMID: 33393489, PMCID: PMC7773383, DOI: 10.1172/jci136542.Peer-Reviewed Original ResearchConceptsNetrin-1Lung fibrosisCell-specific knockout miceΑ1-adrenoreceptor blockadeIPF lung tissueNeuronal guidance proteinsNetrin-1 expressionExtracellular matrix accumulationAdrenergic processesAdrenoreceptor antagonismAdrenoreceptor blockadeFibrotic histologyInflammatory scarringIPF cohortAdrenergic nervesΑ1-blockersImproved survivalColorectal carcinomaLung tissueKnockout miceCollagen accumulationFibrosisMatrix accumulationMacrophagesGuidance proteins
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 mtDNA