Featured Publications
A 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 programAirway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
Jaeger B, Schupp JC, Plappert L, Terwolbeck O, Artysh N, Kayser G, Engelhard P, Adams TS, Zweigerdt R, Kempf H, Lienenklaus S, Garrels W, Nazarenko I, Jonigk D, Wygrecka M, Klatt D, Schambach A, Kaminski N, Prasse A. Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis. Nature Communications 2022, 13: 5637. PMID: 36163190, PMCID: PMC9513076, DOI: 10.1038/s41467-022-33193-0.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway basal cellsPulmonary fibrosisNovel mouse xenograft modelEffect of saracatinibBasal cellsLimited treatment optionsMouse xenograft modelLung developmental processesConnectivity Map analysisExtracellular matrix depositionIPF lungsBronchial brushSevere fibrosisTreatment optionsBronchial brushingsNRG miceHealthy volunteersXenograft modelCyst-like structuresProfibrotic changesAlveolar compartmentFatal diseaseFibrosisPotent Src inhibitorIntegrated 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 populationsThyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function
Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo e Drigo R, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nature Medicine 2017, 24: 39-49. PMID: 29200204, PMCID: PMC5760280, DOI: 10.1038/nm.4447.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 mouse
2024
SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data
Liu Y, Li N, Qi J, Xu G, Zhao J, Wang N, Huang X, Jiang W, Wei H, Justet A, Adams T, Homer R, Amei A, Rosas I, Kaminski N, Wang Z, Yan X. SDePER: a hybrid machine learning and regression method for cell-type deconvolution of spatial barcoding-based transcriptomic data. Genome Biology 2024, 25: 271. PMID: 39402626, PMCID: PMC11475911, DOI: 10.1186/s13059-024-03416-2.Peer-Reviewed Original ResearchINTERACTIONS BETWEEN MITOCHONDRIAL DNA AND TOLL-LIKE RECEPTOR 9 MEDIATES PULMONARY FIBROSIS
LEE C, TRUJILLO G, REGUEIRO-REN A, LIU C, HU B, SUN Y, KHOURY J, KHOURY J, AHANGARI F, ISHIKAWA G, WALIA A, PIVARNIK T, YU S, WOO S, FIORINI V, MCGOVERN J, AL JUMAILY K, SUN H, PENG X, ANTIN-OZERKIS D, SAULER M, KAMINSKI N, HERZOG E. INTERACTIONS BETWEEN MITOCHONDRIAL DNA AND TOLL-LIKE RECEPTOR 9 MEDIATES PULMONARY FIBROSIS. CHEST Journal 2024, 166: a3384-a3386. DOI: 10.1016/j.chest.2024.06.2020.Peer-Reviewed Original ResearchDissecting the immune cell niche in pulmonary sarcoidosis – CXCL10+ monocyte-derived macrophages are potential drivers of TH17.1 inflammation
Ruwisch J, Schupp J, Bartkute B, Artysh N, Kaminski N, Prasse A. Dissecting the immune cell niche in pulmonary sarcoidosis – CXCL10+ monocyte-derived macrophages are potential drivers of TH17.1 inflammation. 2024, oa953. DOI: 10.1183/13993003.congress-2024.oa953.Peer-Reviewed Original ResearchSingle-nuclei RNA-seq reveals aberrant cell populations in restrictive allograft syndrome after lung transplantation
Leiber L, Christian L, Neubert L, Yilmaz H, Kamp J, Plucinski E, Welte T, Falk C, Kaminski N, Jonigk* D, Gottlieb* J, Schupp* J. Single-nuclei RNA-seq reveals aberrant cell populations in restrictive allograft syndrome after lung transplantation. 2024, oa985. DOI: 10.1183/13993003.congress-2024.oa985.Peer-Reviewed Original ResearchToll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.
Trujillo G, Regueiro-Ren A, Liu C, Hu B, Sun Y, Ahangari F, Fiorini V, Ishikawa G, Al Jumaily K, Khoury J, McGovern J, Lee C, Peng X, Pivarnik T, Sun H, Walia A, Woo S, Yu S, Antin-Ozerkis D, Sauler M, Kaminski N, Herzog E, Ryu C. Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2024 PMID: 39189851, DOI: 10.1164/rccm.202401-0065oc.Peer-Reviewed Original ResearchToll-like receptor 9Model of pulmonary fibrosisIdiopathic pulmonary fibrosisPulmonary fibrosisFibroproliferative responseLung diseaseIdiopathic pulmonary fibrosis cohortsExpression of toll-like receptor 9Toll-like receptor 9 activationTransplant-free survivalExpression of MCP-1Cohort of patientsSlow clinical progressionFibrotic lung diseaseAccelerated disease courseFatal lung diseaseIP-10Pharmacodynamic endpointsPreclinical modelsDisease courseClinical progressionPlasma mtDNAMCP-1Receptor 9Mouse modelSpatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2
Bell J, Davies E, Brereton C, Vukmirovic M, Roberts J, Lunn K, Wickens L, Conforti F, Ridley R, Ceccato J, Sayer L, Johnston D, Vallejo A, Alzetani A, Jogai S, Marshall B, Fabre A, Richeldi L, Monk P, Skipp P, Kaminski N, Offer E, Wang Y, Davies D, Jones M. Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2. Cell Reports Medicine 2024, 5: 101695. PMID: 39173635, PMCID: PMC11524965, DOI: 10.1016/j.xcrm.2024.101695.Peer-Reviewed Original ResearchSingle-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 chemoattractantPlasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts
Sand J, Jessen H, Leeming D, Yu S, Lee C, Hu B, Sun Y, Adams T, Pivarnik T, Liu A, Woo S, McGovern J, Fiorini V, Saber T, Higuero-Sevilla J, Gulati M, Kaminski N, Damsky W, Shaw A, Mohanty S, Goobie G, Zhang Y, Herzog E, Ryu C. Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts. Thorax 2024, 79: thorax-2023-221095. PMID: 39117421, DOI: 10.1136/thorax-2023-221095.Peer-Reviewed Original ResearchSarcoidosis cohortMultiorgan diseasePRO-C3Interleukin-4Case Control Etiologic Study of SarcoidosisPlasma levels of interleukin-4Alpha-1 antitrypsin deficiencyLevels of interleukin-4Pathogenesis of sarcoidosisC6MC3MHealthy control patientsStudy of sarcoidosisGenomic researchAbnormal extracellular matrixAssociated with dermatological diseaseCollagen degradationScadding stageCorticosteroid useComplex diseasesPRO-C6Control patientsIL-13IL-5IL-9Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Zhao A, Unterman A, Abu Hussein N, Sharma P, Nikola F, Flint J, Yan X, Adams T, Justet A, Sumida T, Zhao J, Schupp J, Raredon M, Ahangari F, Deluliis G, Zhang Y, Buendia-Roldan I, Adegunsoye A, Sperling A, Prasse A, Ryu C, Herzog E, Selman M, Pardo A, Kaminski N. Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 1252-1266. PMID: 38924775, PMCID: PMC11568434, DOI: 10.1164/rccm.202401-0078oc.Peer-Reviewed Original ResearchFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsBronchoalveolar lavage cellsBlood mononuclear cellsClassical monocytesHypersensitivity pneumonitisPulmonary fibrosisT cellsImmune perturbationsLavage cellsMononuclear cellsCD8+ T cellsCytotoxic T cellsInterstitial lung diseaseHypersensitivity pneumonitis patientsCytotoxic CD4Immune aberrationsPneumonic patientsPneumonitisLung diseaseHealthy controlsImmune mechanismsPatient cellsSingle-cell transcriptomicsNoninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1
Mannes P, Adams T, Farsijani S, Barnes C, Latoche J, Day K, Nedrow J, Ahangari F, Kaminski N, Lee J, Tavakoli S. Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1. Science Advances 2024, 10: eadm9817. PMID: 38896611, PMCID: PMC11186491, DOI: 10.1126/sciadv.adm9817.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisFibrotic lung diseaseRisk stratificationMurine modelLung fibrosisLung diseaseModel of bleomycin-induced lung fibrosisBleomycin-induced lung fibrosisImaging biomarkersMurine model of bleomycin-induced lung fibrosisBronchoalveolar lavage cellsMonocyte-derived macrophagesPositron emission tomographyInflammatory endotypesPulmonary fibrosisLavage cellsPoor survivalNoninvasive assessmentTherapeutic monitoringEmission tomographyCMKLR1FibrosisClinical trajectoryLungLung regionsUnderstanding the Added Value of High-Resolution CT Beyond Chest X-Ray in Determining Extent of Physiologic Impairment
Benn B, Lippitt W, Cortopassi I, Balasubramani G, Barbosa E, Drake W, Herzog E, Gibson K, Chen E, Koth L, Fuhrman C, Lynch D, Kaminski N, Wisniewski S, Carlson N, Maier L. Understanding the Added Value of High-Resolution CT Beyond Chest X-Ray in Determining Extent of Physiologic Impairment. CHEST Journal 2024, 166: 1093-1107. PMID: 38830401, PMCID: PMC11560486, DOI: 10.1016/j.chest.2024.04.031.Peer-Reviewed Original ResearchScadding stageCT featuresLung functionChest radiologistsCT scanAlpha-1 anti-trypsin deficiencyChest computed tomographyChest CT scanChest X-rayIncreasing clinical useCompare demographic featuresAssociated with FEV1Visual scoring systemSarcoidosis stagePulmonary sarcoidosisChest CTCT findingsAssociated with lung functionCT assessmentComputed tomographySarcoidosisClinical useRadiological measurementsCT measurementsScoring systemSingle-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury
Yuan Y, Sharma L, Tang W, Raredon M, Ahangari F, Khoury J, Wu D, Niklason L, Kaminski N. Single-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury. Physiology 2024, 39: 1314. DOI: 10.1152/physiol.2024.39.s1.1314.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisAcute lung injuryChronic obstructive pulmonary diseaseAcute respiratory distress syndromeAnalysis of cell-cell communicationVEGF-DMicrovascular nicheSingle-cell RNA-seqLung injury modelSingle-cell RNA-seq analysisLung injuryCell-cell communicationLigand-receptor pairsLPS-induced lung injury modelRNA-seqAdjacent cell typesPulmonary diseaseInjury modelHuman lung endothelial cellsBarrier functionImmune cell infiltrationTumor necrosis factor-aRespiratory distress syndromeLung vascular integrityGene expressionCollagen Prolyl-3-hydroxylase 1 Controls Collagen Quality and Extracellular Matrix Deposition
Staab-Weijnitz C, Hennen E, Sarohi V, Pijadina K, Binzenhöfer L, Cabeza-Boeddinghaus N, Merl-Pham J, Onursal C, Jentsch R, Behr J, Gote-Schniering J, Schiller H, Hilgendorff A, Bächinger H, Hauck S, Kaminski N, Eickelberg O, Vanacore R, Basak T. Collagen Prolyl-3-hydroxylase 1 Controls Collagen Quality and Extracellular Matrix Deposition. 2024, a5192-a5192. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5192.Peer-Reviewed Original ResearchNebulizable Conjugates to Sustain Retention, Delivery, and Efficacy of Galectin-3 Inhibitory Drug TD139 in the Alveolar Space
Marti Munoz J, Khoury J, Ahangari F, Deiuliis G, Kaminski N, Pandit A. Nebulizable Conjugates to Sustain Retention, Delivery, and Efficacy of Galectin-3 Inhibitory Drug TD139 in the Alveolar Space. 2024, a3218-a3218. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a3218.Peer-Reviewed Original ResearchsnRNAseq of IPF Stromal Cells Reveals Dysfunctional Gene Co-expression Profile
Sharma P, Taylor S A, Anderson S, Nekola F, Giuseppe D, Yan X, Schupp J, Balayev A, Justet A, Wuyts W, Vanaudenaerde B, Kaminski N. snRNAseq of IPF Stromal Cells Reveals Dysfunctional Gene Co-expression Profile. 2024, a4903-a4903. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4903.Peer-Reviewed Original Research