2024
A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma
Everman J, Sajuthi S, Liegeois M, Jackson N, Collet E, Peters M, Chioccioli M, Moore C, Patel B, Dyjack N, Powell R, Rios C, Montgomery M, Eng C, Elhawary J, Mak A, Hu D, Huntsman S, Salazar S, Feriani L, Fairbanks-Mahnke A, Zinnen G, Michel C, Gomez J, Zhang X, Medina V, Chu H, Cicuta P, Gordon E, Zeitlin P, Ortega V, Reisdorph N, Dunican E, Tang M, Elicker B, Henry T, Bleecker E, Castro M, Erzurum S, Israel E, Levy B, Mauger D, Meyers D, Sumino K, Gierada D, Hastie A, Moore W, Denlinger L, Jarjour N, Schiebler M, Wenzel S, Woodruff P, Rodriguez-Santana J, Pearson C, Burchard E, Fahy J, Seibold M. A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma. Nature Communications 2024, 15: 3900. PMID: 38724552, PMCID: PMC11082194, DOI: 10.1038/s41467-024-48034-5.Peer-Reviewed Original ResearchConceptsAirway epithelial cellsIntelectin-1Mucus pluggingGene expressionAirways of severe asthmaticsEpithelial cellsHuman airway epithelial cellsAirway epithelial brushingsMucus secretory cellsT2-high asthmaFormation of mucus plugsAssociated with protectionC-terminusGenetic variantsAirway mucus pluggingMolecular roleSecretory cellsSecreted componentsEpithelial brushingsT2-lowIL-13Mucus obstructionTarget pathwaysSevere asthmaticsClinical significanceStem cell migration drives lung repair in living mice
Chioccioli M, Liu S, Magruder S, Tata A, Borriello L, McDonough J, Konkimalla A, Kim S, Nouws J, Gonzalez D, Traub B, Ye X, Yang T, Entenberg D, Krishnaswamy S, Hendry C, Kaminski N, Tata P, Sauler M. Stem cell migration drives lung repair in living mice. Developmental Cell 2024, 59: 830-840.e4. PMID: 38377991, PMCID: PMC11003834, DOI: 10.1016/j.devcel.2024.02.003.Peer-Reviewed Original ResearchStem cell migrationCell migrationAlveolar type 2 cellsAlveolar unitsStem cell motilityAlveolar type 1 cellsStem cell activityCellular response to injuryResponse to injuryType 2 cellsMotile phenotypeType 1 cellsCell motilityLung repairImpaired regenerationGenetic depletionCell activationAT2Stem cellsTissue repairAT1Longitudinal imagingInjuryMotilityCellular resolution
2023
Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells.
Schupp J, Manning E, Chioccioli M, Kamp J, Christian L, Ryu C, Herzog E, Kühnel M, Prasse A, Kaminski N, Jonigk D, Homer R, Neubert L, Ius F, stringJustet A, Hariri L, Seeliger B, Welte T, Knipe R, Gottlieb J. Alveolar Vascular Remodeling in Nonspecific Interstitial Pneumonia: Replacement of Normal Lung Capillaries with COL15A1-Positive Endothelial Cells. American Journal Of Respiratory And Critical Care Medicine 2023, 208: 819-822. PMID: 37552025, PMCID: PMC10563189, DOI: 10.1164/rccm.202303-0544le.Peer-Reviewed Original ResearchMicroRNA-1 protects the endothelium in acute lung injury
Korde A, Haslip M, Pednekar P, Khan A, Chioccioli M, Mehta S, Lopez-Giraldez F, Bermejo S, Rojas M, Dela Cruz C, Matthay M, Pober J, Pierce R, Takyar S. MicroRNA-1 protects the endothelium in acute lung injury. JCI Insight 2023, 8: e164816. PMID: 37737266, PMCID: PMC10561733, DOI: 10.1172/jci.insight.164816.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeAcute lung injuryVascular endothelial growth factorAngiopoietin-2Lung injuryAcute injuryMiR-1MicroRNA-1Endothelial cell-specific overexpressionSevere endothelial dysfunctionRespiratory distress syndromeSurvival of miceIntrinsic protective effectContext of injuryCell-specific overexpressionEndothelial growth factorFamily member 3Pneumonia cohortMiR-1 targetsEndothelial dysfunctionDistress syndromeBarrier dysfunctionCapillary leakProtective effectSevere formMild Phenotypes in French-Canadians With TT25-related Primary Ciliary Dyskinesia
Palani M, Ding S, Ma K, Lek M, Vinh D, Henry M, Knowles M, Zariwala M, Leigh M, Chioccioli M, Shapiro A. Mild Phenotypes in French-Canadians With TT25-related Primary Ciliary Dyskinesia. 2023, a6109-a6109. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a6109.Peer-Reviewed Original ResearchmicroRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mousePhototaxis of Chlamydomonas arises from a tuned adaptive photoresponse shared with multicellular Volvocine green algae
Leptos K, Chioccioli M, Furlan S, Pesci A, Goldstein R. Phototaxis of Chlamydomonas arises from a tuned adaptive photoresponse shared with multicellular Volvocine green algae. Physical Review E 2023, 107: 014404. PMID: 36797913, PMCID: PMC7616094, DOI: 10.1103/physreve.107.014404.Peer-Reviewed Original ResearchConceptsVolvocine algaeGreen algaeVolvocine green algaeMulticellular speciesMulticellular organismsEvolutionary transitionsChlamydomonasVolvoxAlgaeIndividual flagellaExtracellular matrixIndividual cellsIntercellular connectionsAdaptive responsePrimary axisGoniumSwimming cellsLight levelsPhototaxisOrganismsSpeciesFlagellar responsesCell numberCellsBeat plane
2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Ahangari F, Becker C, Foster DG, Chioccioli M, Nelson M, Beke K, Wang X, Justet A, Adams T, Readhead B, Meador C, Correll K, Lili LN, Roybal HM, Rose KA, Ding S, Barnthaler T, Briones N, DeIuliis G, Schupp JC, Li Q, Omote N, Aschner Y, Sharma L, Kopf KW, Magnusson B, Hicks R, Backmark A, Dela Cruz CS, Rosas I, Cousens LP, Dudley JT, Kaminski N, Downey GP. Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1463-1479. PMID: 35998281, PMCID: PMC9757097, DOI: 10.1164/rccm.202010-3832oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisHuman precision-cut lung slicesPrecision-cut lung slicesPulmonary fibrosisNormal human lung fibroblastsEpithelial-mesenchymal transitionHuman lung fibroblastsFibrogenic pathwaysPreclinical modelsMurine modelLung slicesSrc kinase inhibitorLung fibroblastsKinase inhibitorsAmelioration of fibrosisSelective Src kinase inhibitorHuman lung fibrosisWhole lung extractsPotential therapeutic efficacyIPF diseaseIPF treatmentLung functionInflammatory cascadeLung fibrosisAntifibrotic efficacyA lung targeted miR-29 mimic as a therapy for pulmonary fibrosis
Chioccioli M, Roy S, Newell R, Pestano L, Dickinson B, Rigby K, Herazo-Maya J, Jenkins G, Ian S, Saini G, Johnson SR, Braybrooke R, Yu G, Sauler M, Ahangari F, Ding S, DeIuliis J, Aurelien N, Montgomery RL, Kaminski N. A lung targeted miR-29 mimic as a therapy for pulmonary fibrosis. EBioMedicine 2022, 85: 104304. PMID: 36265417, PMCID: PMC9587275, DOI: 10.1016/j.ebiom.2022.104304.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNon-human primatesPulmonary fibrosisAnimal modelsPro-fibrotic genesAnti-fibrotic efficacyMiR-29 mimicsHuman peripheral bloodMiR-29b levelsHuman lung fibroblastsIPF patientsIPF diagnosisPeripheral bloodReduced fibrosisAdverse findingsPotential therapyLung slicesTGF-β1Relevant dosesLung fibroblastsNIH-NHLBIFibrosisTherapyCollagen productionProfibrotic gene programMicroRNA-1 Regulates an Endothelial Gene Network Controlling Permeability and Alveolar Cell Death
Korde A, Haslip M, Chioccioli M, Khan A, Mehta S, Pober J, Pierce R, Takyar S. MicroRNA-1 Regulates an Endothelial Gene Network Controlling Permeability and Alveolar Cell Death. 2022, a5771-a5771. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5771.Peer-Reviewed Original ResearchCharacterization 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
Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung
Schupp JC, Adams TS, Cosme C, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe’er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung. Circulation 2021, 144: 286-302. PMID: 34030460, PMCID: PMC8300155, DOI: 10.1161/circulationaha.120.052318.Peer-Reviewed Original ResearchConceptsDifferential expression analysisPrimary lung endothelial cellsLung endothelial cellsCell typesMarker genesExpression analysisSingle-cell RNA sequencing dataCross-species analysisVenous endothelial cellsEndothelial marker genesSingle-cell atlasMarker gene setsRNA sequencing dataEndothelial cellsSubsequent differential expression analysisDifferent lung cell typesResident cell typesLung cell typesCellular diversityEndothelial cell typesCapillary endothelial cellsHuman lung endothelial cellsPhenotypic diversityEndothelial diversityIndistinguishable populationsLong noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state
Omote N, Sakamoto K, Li Q, Schupp JC, Adams T, Ahangari F, Chioccioli M, DeIuliis G, Hashimoto N, Hasegawa Y, Kaminski N. Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state. Physiological Reports 2021, 9: e14727. PMID: 33527707, PMCID: PMC7851438, DOI: 10.14814/phy2.14727.Peer-Reviewed Original ResearchConceptsTerminal differentiation-induced lncRNANormal human bronchial epithelial cellsTINCR overexpressionCell differentiationNotch genesTissue developmentBronchial epithelial cellsExtracellular matrix organizationCell phenotypeRNA sequencing analysisNumerous biological functionsRole of lncRNAsCell differentiation stateEpithelial cellsHuman bronchial epithelial cellsCiliated cell differentiationStaufen1 proteinNovel regulatorBasal cell phenotypeDownstream regulatorsRNA immunoprecipitationBiological functionsCritical regulatorDifferential expressionDifferentiation stateMicroRNA 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 and Population Transcriptomics Reveal Pan-epithelial Remodeling in Type 2-High Asthma
Jackson ND, Everman JL, Chioccioli M, Feriani L, Goldfarbmuren KC, Sajuthi SP, Rios CL, Powell R, Armstrong M, Gomez J, Michel C, Eng C, Oh SS, Rodriguez-Santana J, Cicuta P, Reisdorph N, Burchard EG, Seibold MA. Single-Cell and Population Transcriptomics Reveal Pan-epithelial Remodeling in Type 2-High Asthma. Cell Reports 2020, 32: 107872. PMID: 32640237, PMCID: PMC8046336, DOI: 10.1016/j.celrep.2020.107872.Peer-Reviewed Original ResearchConceptsIL-13Single-cell RNA sequencingHuman airway epithelial cell culturesCell typesIL-13 effectsAirway epithelial cell culturesNasal airway epitheliumCandidate therapeutic targetTranscriptional statesAsthmatic childrenAsthma endotypesRNA sequencingMucus obstructionAirway epitheliumSecretory programMucin productionNormal epithelial functionTherapeutic targetEpithelial cell culturesCellular remodelingER stressCell deathEpithelial functionMetaplastic stateSecretory cellsIntelectin-1 Affects Interleukin-13-Induced Mucociliary Airway Dysfunction and Its Expression Is Regulated by a Cis-eQTL Associated with Development of Asthma and IBD
Everman J, Jackson N, Sajuthi S, Saef B, Chioccioli M, Dyjack N, Powell R, Rios C, Montgomery M, Oh S, Eng C, Elhawary J, Feriani L, Armstrong M, Gomez J, Zhang X, Medina V, Chu H, Cicuta P, Rodriguez-Santana J, Reisdorph N, Burchard E, Seibold M. Intelectin-1 Affects Interleukin-13-Induced Mucociliary Airway Dysfunction and Its Expression Is Regulated by a Cis-eQTL Associated with Development of Asthma and IBD. 2020, a7400-a7400. DOI: 10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7400.Peer-Reviewed Original Research
2019
Quantitative High-Speed Video Profiling Discriminates between DNAH11 and HYDIN Variants of Primary Ciliary Dyskinesia
Chioccioli M, Feriani L, Nguyen Q, Kotar J, Dell SD, Mennella V, Amirav I, Cicuta P. Quantitative High-Speed Video Profiling Discriminates between DNAH11 and HYDIN Variants of Primary Ciliary Dyskinesia. American Journal Of Respiratory And Critical Care Medicine 2019, 199: 1436-1438. PMID: 31116566, DOI: 10.1164/rccm.201812-2256le.Peer-Reviewed Original ResearchQuantitative High Speed Video Profiling Discriminates Between Variants of Primary Ciliary Dyskinesia
Chioccioli M, Feriani L, Nguyen Q, Kotar J, Dell S, Mennella V, Amirav I, Cicuta P. Quantitative High Speed Video Profiling Discriminates Between Variants of Primary Ciliary Dyskinesia. 2019, a5883-a5883. DOI: 10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a5883.Peer-Reviewed Original ResearchPhenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells
Chioccioli M, Feriani L, Kotar J, Bratcher PE, Cicuta P. Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells. Nature Communications 2019, 10: 1763. PMID: 30992452, PMCID: PMC6467870, DOI: 10.1038/s41467-019-09798-3.Peer-Reviewed Original ResearchConceptsHuman airway epithelial cellsEpithelial cellsCystic fibrosis respiratory epithelial cellsAirway epithelial cellsRespiratory epithelial cellsCiliary beat frequencyCiliary beatingRespiratory disordersRespiratory diseaseClinical observationsCystic fibrosisDrug efficacyPilot studyDrug testingEfficient drugsDrugsIndividual donorsEfficacyDrug screeningBeat dynamicsCellsSame genotypeFibrosisDonorsDiseaseA How-To guide to: Quantitative high-speed video profiling to discriminate between variants of primary ciliary dyskinesia
https://doi.org/10.1101/614966Peer-Reviewed Original Research