2025
A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases
Zheng Y, Schupp J, Adams T, Clair G, Justet A, Ahangari F, Yan X, Hansen P, Carlon M, Cortesi E, Vermant M, Vos R, De Sadeleer L, Rosas I, Pineda R, Sembrat J, Königshoff M, McDonough J, Vanaudenaerde B, Wuyts W, Kaminski N, Ding J. A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases. Nature Biomedical Engineering 2025, 1-26. PMID: 40542107, DOI: 10.1038/s41551-025-01423-7.Peer-Reviewed Original ResearchComplex cellular dynamicsCellular dynamicsSingle-cell transcriptomic dataIn silico drug discoverySingle-cell transcriptomicsTranscriptome dataPotential therapeutic drug candidateComplex diseasesHuman diseasesIdiopathic pulmonary fibrosisTherapeutic drug candidateCell embeddingDrug discoveryPulmonary fibrosisDrug candidatesDisease progressionHuman tissuesHuman precision-cut lung slicesDynamic analysisPrecision-cut lung slicesPathological landscapeComputational toolsAnti-fibrotic effectsUnagiTranscriptomeRaman Spectroscopy Detects Differences Between Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Disease Biopsies
Marti Munoz J, Owens P, Contessotto P, Xiting Y, Balayev A, Serrano M, Dockery P, Kaminski N, Pandit A. Raman Spectroscopy Detects Differences Between Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Disease Biopsies. American Journal Of Respiratory And Critical Care Medicine 2025, 211: a4661-a4661. DOI: 10.1164/ajrccm.2025.211.abstracts.a4661.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisPulmonary fibrosisDeupirfenidone Compared to Placebo and Pirfenidone in Idiopathic Pulmonary Fibrosis: ELEVATE IPF Phase 2b Trial
Maher T, Bergna M, Hajari Case A, Choi W, Hamblin M, Kulkarni T, Shore J, Tomos I, Tzouvelekis A, Golod D, Elenko E, Zhang Y, Graham C, Song J, ELEVATE IPF Investigators. Deupirfenidone Compared to Placebo and Pirfenidone in Idiopathic Pulmonary Fibrosis: ELEVATE IPF Phase 2b Trial. American Journal Of Respiratory And Critical Care Medicine 2025, 211: a7046-a7046. DOI: 10.1164/ajrccm.2025.211.abstracts.a7046.Peer-Reviewed Original ResearchApplying single cell profiling to assess drug anti fibrotic properties in the human precision cut lung slice model of fibrosis
Justet A, Mitash N, Pineda R, Adams T, Balayev A, Abu Hussein N, Ishizuka M, Kim H, Khoury J, Cala-García J, Ahangari F, Yan X, Kaminski N, Königshoff M. Applying single cell profiling to assess drug anti fibrotic properties in the human precision cut lung slice model of fibrosis. Revue Des Maladies Respiratoires 2025, 42: 223. DOI: 10.1016/j.rmr.2025.02.083.Peer-Reviewed Original ResearchAbnormal cell populationsAlveolar epithelial cellsTreated with drugsAnti-fibrotic propertiesSingle cell platformsSingle nuclear RNA sequencingLigand-receptor analysisPreclinical evidencePulmonary fibrosisBasaloid cellsFibrotic propertiesReceptor analysisFibrotic pathwaysCell signaturesClinical trialsProfibrotic genesAnti-fibroticFDA-approved drugsGene signatureAnimal modelsEpithelial cellsGene expression changesDay 5Drug efficacyCell profileseNAMPT Is a Novel DAMP and Therapeutic Target in Human and Murine Pulmonary Fibrosis.
Casanova N, Herazo-Maya J, Kempf C, Sun B, Song J, Hernandez A, Canizales Galaviz J, Sun X, Camp S, Ledford J, Hellinger R, Rodriguez M, Zhao A, Unterman A, Rosas I, Duncan S, Thannickal V, Hufford M, Ahmed M, Zaghloul N, Gupta A, Bime C, Sammani S, Stansfield B, Chen J, Anandhan A, Disney M, Ooi A, Kee S, Karampitsakos T, Benos P, Kaminski N, Zhang D, Garcia J. eNAMPT Is a Novel DAMP and Therapeutic Target in Human and Murine Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2025 PMID: 40126452, DOI: 10.1165/rcmb.2024-0342oc.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisExtracellular nicotinamide phosphoribosyltransferaseDamage-associated molecular pattern proteinToll-like receptor 4Lung tissuePulmonary fibrosisBleomycin-induced lung fibrosis modelNASH-associated hepatic fibrosisIdiopathic pulmonary fibrosis subjectsRadiation-induced lung fibrosisIdiopathic pulmonary fibrosis patientsBleomycin-exposed miceIdentification of novel therapeuticsLung fibrosis modelMurine lung tissueMurine pulmonary fibrosisLung fibrosis developmentCurative therapyGene expressionC57BL6 miceLung fibrosisIPF treatmentFatal disorderHuman PBMCsFibrosis developmentFGF21 Signaling Exerts Antifibrotic Properties during Pulmonary Fibrosis.
Ghanem M, Archer G, Justet A, Jaillet M, Vasarmidi E, Mordant P, Castier Y, Mal H, Cazes A, Poté N, Crestani B, Mailleux A. FGF21 Signaling Exerts Antifibrotic Properties during Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2025, 211: 486-498. PMID: 39637324, DOI: 10.1164/rccm.202311-2021oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisWild-type littermatesPlasma of patientsPulmonary fibrosisAntifibrotic propertiesIntratracheal injection of bleomycinDevelopment of pulmonary fibrosisDecreased fibrosis markersEffects of FGF21Increased sensitivity to bleomycinInjection of bleomycinPulmonary fibrosis developmentSensitivity to bleomycinDecrease of BaxConcentrations of FGF21Human lung fibroblastsTherapeutic optionsFibrosis markersAntifibrotic effectsControl subjectsInjury scoreIntratracheal injectionLiver fibrosisLung fibrogenesisFibroblast growth factorChanges in Lung Function and Mortality Risk in Patients With Idiopathic Pulmonary Fibrosis
Oldham J, Neely M, Wojdyla D, Gulati M, Li P, Patel D, Palmer S, Todd J, Investigators I. Changes in Lung Function and Mortality Risk in Patients With Idiopathic Pulmonary Fibrosis. CHEST Journal 2025 PMID: 40020995, DOI: 10.1016/j.chest.2025.02.018.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisLung transplantationLung function declinePulmonary fibrosisAssociated with 1.8-foldProgressive fibrosing interstitial lung diseaseMedian follow-up timeFibrosing interstitial lung diseaseFollow-up timeInterstitial lung diseaseCox proportional hazards modelsRisk of deathFunctional declineRisk of mortalityProportional hazards modelAntifibrotic treatmentThreshold of declineAssociated with lung function declineOutcomes RegistryLung diseaseEnrolling centersDLCOSmoking statusDiffusing capacityLung functionEpigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks
Kurbanov D, Ahangari F, Adams T, De Man R, Tang J, Carlon M, Abu Hussein N, Cortesi E, Zapata M, De Sadelaar L, Wuyts W, Vanaudenaerde B, Kaminski N, McDonough J. Epigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2025, 328: l456-l462. PMID: 39970931, PMCID: PMC12169420, DOI: 10.1152/ajplung.00171.2024.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIdiopathic pulmonary fibrosis tissuePulmonary fibrosisLung tissueEpigenetic clocksPotential of DNA methylationDNA methylation levelsDebilitating lung diseaseIllumina MethylationEPIC arrayHuman lung tissueEpigenetic ageDNA methylation clocksBiological ageAffected lung tissueIPF casesClinical prognosisMethylation patternsDNA methylationLung diseaseHealthy controlsAcceleration of biological agingMethylation levelsMethylationEPIC arrayAge accelerationClinical assessmentCD103+ dendritic cell — fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis
Carter H, Costa R, Adams T, Gilchrist T, Emch C, Bame M, Oldham J, Huang S, Linderholm A, Noth I, Kaminski N, Moore B, Gurczynski S. CD103+ dendritic cell — fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis. JCI Insight 2025, 10 PMID: 39964756, PMCID: PMC11949071, DOI: 10.1172/jci.insight.177072.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBasic Helix-Loop-Helix Transcription FactorsBleomycinDendritic CellsDisease Models, AnimalFibroblastsHumansIdiopathic Pulmonary FibrosisIntegrin alpha ChainsInterleukin-6LungMaleMiceMice, Inbred C57BLReceptors, Aryl HydrocarbonSignal TransductionToll-Like Receptor 9Tryptophan OxygenaseConceptsIdiopathic pulmonary fibrosisAhR signalingMice treated with BLMIL-17+ cellsCD103+ DCLoss of lung functionStudies of human samplesLimited treatment optionsTreated ex vivoProduction of IL-6Inflammatory cytokine productionExon 2 deletionExpression of TDO2IL-6 productionAdoptive transferCD11c-CreCD11c+ cellsImmunological changesPulmonary fibrosisTLR agonistsProgressive scarringTreatment optionsCytokine productionLung fibrogenesisAryl hydrocarbon receptorInvestigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis
Spagnolo P, Tonelli R, Mura M, Reisman W, Sotiropoulou V, Tzouvelekis A. Investigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis. Expert Opinion On Investigational Drugs 2025, 34: 61-80. PMID: 39916340, DOI: 10.1080/13543784.2025.2462592.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisGene therapyPulmonary fibrosisAssociated with tolerability issuesProgressive fibrosing interstitial lung diseaseEfficacy of gene therapyApplication of gene therapyTreatment of idiopathic pulmonary fibrosisLong-term clinical dataFibrosing interstitial lung diseaseFirst-line therapyImproved vector designInterstitial lung diseaseMitigate off-target effectsTolerated treatmentDismal prognosisClinical dataLung diseaseClinical studiesAssociated with poor qualityProfibrotic pathwaysTarget cellsTherapyFibrosisOff-target effectsCollagen Hybridizing Peptide-Based Radiotracers for Molecular Imaging of Collagen Turnover in Pulmonary Fibrosis.
Ahmad A, Ghim M, Kukreja G, Neishabouri A, Zhang Z, Li J, Salarian M, Toczek J, Gona K, Hedayatyanfard K, Morrison T, Zhang J, Huang Y, Liu C, Yu S, Sadeghi M. Collagen Hybridizing Peptide-Based Radiotracers for Molecular Imaging of Collagen Turnover in Pulmonary Fibrosis. Journal Of Nuclear Medicine 2025, 66: 425-433. PMID: 39915119, PMCID: PMC11876730, DOI: 10.2967/jnumed.124.268832.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisTracer uptakeLung uptakeMurine model of pulmonary fibrosisModel of pulmonary fibrosisMice 3 wkEffect of antifibrotic therapyCollagen turnoverInterstitial lung diseaseClinical diagnostic methodsSPECT/CT imagingHybrid tracersLung histologyAntifibrotic therapyControl miceDisease activityMurine modelLung diseaseMice 8Tissue fibrosisPatient managementLiver uptakeSPECT/CTFibrosisSPECT imagesContinued Treatment with Nintedanib in Patients with Progressive Pulmonary Fibrosis: Data from INBUILD-ON
Wuyts W, Bonella F, Chaudhuri N, Varone F, Antin-Ozerkis D, Song J, Miede C, Dumistracel M, Coeck C, Cottin V. Continued Treatment with Nintedanib in Patients with Progressive Pulmonary Fibrosis: Data from INBUILD-ON. Lung 2025, 203: 25. PMID: 39789408, PMCID: PMC11717875, DOI: 10.1007/s00408-024-00778-z.Peer-Reviewed Original ResearchConceptsProgressive pulmonary fibrosisForced Vital CapacityAdverse eventsSafety profilePulmonary fibrosisConclusionThe safety profileDiscontinuation of nintedanibExposure to nintedanibSafety of nintedanibOpen-label extensionBaseline to weekFrequent adverse eventsFatal adverse eventsLong-term treatmentLonger-term treatmentNintedanib groupGastrointestinal eventsINBUILD trialNintedanibMethodsAdverse eventsModerate severityPatientsContinuous treatmentVital capacityINBUILDTranscriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis
Divolis G, Synolaki E, Tringidou R, Tzouvelekis A, Boumpas D, Skendros P, Galani I. Transcriptomic analysis reveals shared deregulated neutrophil responses in COVID-19 and idiopathic pulmonary fibrosis. Respiratory Research 2025, 26: 213. PMID: 40500689, PMCID: PMC12160113, DOI: 10.1186/s12931-025-03180-2.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosis patientsIdiopathic pulmonary fibrosisNeutrophil extracellular trapsPulmonary fibrosisIPF pathophysiologyPeripheral blood neutrophil countElevated peripheral blood neutrophil countsAcute respiratory distress syndromeCOVID-19 neutrophilsPeripheral blood of COVID-19 patientsLung biopsy specimensBlood of COVID-19 patientsRespiratory distress syndromeDeregulated immune responseNeutrophil extracellular trap formationBlood neutrophil countNeutrophil-driven pathologiesCOVID-19 pathogenesisCOVID-19 patientsLung biopsyBiopsy specimensDistress syndromePeripheral bloodNeutrophil countActivin/follistatin system
2024
Positron emission tomography an imaging biomarker in pulmonary fibrosis: from therapeutic mechanism to treatment monitoring
Cho S, Herzog E, Thorn S, Sinusas A. Positron emission tomography an imaging biomarker in pulmonary fibrosis: from therapeutic mechanism to treatment monitoring. EBioMedicine 2024, 111: 105519. PMID: 39700895, PMCID: PMC11718319, DOI: 10.1016/j.ebiom.2024.105519.Peer-Reviewed Original ResearchThe effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice
McGovern J, Perry C, Ghincea A, Herzog E, Shao S, Sun H. The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 328: l15-l29. PMID: 39470613, PMCID: PMC11905795, DOI: 10.1152/ajplung.00062.2024.Peer-Reviewed Original ResearchLung fibrosisSurgical adrenalectomyBronchoalveolar lavageLung tissueBleomycin-Induced Pulmonary FibrosisAlpha-smooth muscle actinModel of lung fibrosisBleomycin model of lung fibrosisProgressive lung fibrosisLimited treatment optionsSmooth muscle actinWild type miceEffects of adrenalectomyProduction of catecholaminesDecrease of lymphocytesAdrenal ablationAldosterone levelsBleomycin administrationBleomycin modelSham surgeryAld levelsLung remodelingPulmonary fibrosisType miceAdrenal glandIdentification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis
Ghanem M, Justet A, Jaillet M, Vasarmidi E, Boghanim T, Hachem M, Vadel A, Joannes A, Mordant P, Balayev A, Adams T, Mal H, Cazes A, Poté N, Mailleux A, Crestani B. Identification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 327: l818-l830. PMID: 39350729, DOI: 10.1152/ajplung.00184.2023.Peer-Reviewed Original ResearchWild type littermatesFibroblast growth factorMurine embryonic fibroblastsEndothelin-1Pulmonary fibrosisFGFR4 inhibitionBleomycin-Induced Pulmonary FibrosisIn vitroMyofibroblast differentiationBleomycin-induced lung fibrosisPulmonary fibrosis in vivoTGF-bLung fibroblastsPro-fibrotic propertiesProtein levelsIn vivoAnti-fibrotic propertiesFibrosis in vivoRegulation of myofibroblast differentiationDevelopment of bleomycin-induced lung fibrosisWT miceTherapeutic optionsHuman lung fibroblastsIPF lungsLung fibrosisAcute exacerbations in patients with progressive pulmonary fibrosis
Kreuter M, Belloli E, Bendstrup E, Cerri S, Flaherty K, Shapera S, Song J, Mueller H, Rohr K, Kondoh Y, investigators O, Quadrelli S, Otaola M, Bergna M, Elias P, Arce G, Cazaux A, Guiot J, Bondue B, Dahlqvist C, Homik L, Shapera S, Cantin A, Kolb M, Fénero M, Rozas R, Orellana A, Xu Z, Luo Q, Kang J, Cai H, Marchand-Adam S, Bergot E, Gamez-Dubuis A, Riviere F, Kessler R, Nunes H, Marquette C, Wemeau L, Jouneau S, Lebargy F, Crestani B, Cottin V, Reynaud-Gaubert M, Blaas S, Bonella F, Randerath W, Hetzel J, Koschel D, Kreuter M, Prasse A, Skowasch D, Stieglitz S, Refini R, Cerri S, Pesci A, Tomassetti S, Vancheri C, Varone F, Sakamoto N, Abe S, Hayashi H, Saito T, Suda T, Kitamura H, Okamoto M, Kondoh Y, Makino S, Takeuchi T, Yamada Y, Kono C, Inoue Y, Sugiura H, Kishi K, Takaya H, Yamauchi H, Ichikado K, Tomii K, Takahashi H, Izumi S, Kawamura T, Nishioka Y, Miyazaki Y, Song J, Park J, Kim Y, Jassem E, Kus J, Piotrowski W, Barczyk A, Ziora D, Bazdyrev E, Moiseev S, Avdeev S, Ilkovich M, Yakusevich V, Valenzuela C, Acosta O, Martínez M, Gómez L, Molina-Molina M, Villegas D, Aburto M, Portal J, Villar A, Jiménez A, Sauleda J, Arias M, Beirne P, Stone H, Hope-Gill B, Hirani N, Chaudhuri N, Gifford A, Jones L, Morrison L, Antin-Ozerkis D, Bhatt N, Kulkarni T, Moua T, Ettinger N, Pitts L, Veeraraghavan S, Padilla M, Pérez E, Giessel G, Strek M, Danoff S, Burk J, Rossman M, Patel N, Belloli E, Hotchkin D, Weigt S, Scholand M, Kaner R, Sigal B, Safdar Z, Tolle L, Martinez R, Glassberg M, Hallowell R, Golden J, Schwartz M, Britt E, Morrow L, Mageto Y, Buch K, Chaaban S, Poonyagariyagorn H, Dilling D, Shlobin O, Thavarajah K, Nambiar A, Rosas I, Bascom R, Oldham J, Schmidt S, D'Amico J, Falk J, Glazer C, Criner G. Acute exacerbations in patients with progressive pulmonary fibrosis. ERJ Open Research 2024, 10: 00403-2024. PMID: 39624387, PMCID: PMC11610068, DOI: 10.1183/23120541.00403-2024.Peer-Reviewed Original ResearchProgressive pulmonary fibrosisInterstitial lung diseaseIdiopathic pulmonary fibrosisAcute exacerbationPulmonary fibrosisAcute exacerbation of idiopathic pulmonary fibrosisExacerbation of idiopathic pulmonary fibrosisHazard ratioFibrosing ILDsProgressive fibrosing ILDsRisk factorsRisk of acute exacerbationIncreased risk of acute exacerbationAssociated with high mortalityMedian Follow-UpKaplan-Meier methodCox proportional hazards modelsInvestigate risk factorsRisk of deathProportional hazards modelRisk factor analysisPrognostic impactINBUILD trialBaseline characteristicsFollow-upCross-tissue organization of myeloid cells in scleroderma and related fibrotic diseases
Odell I. Cross-tissue organization of myeloid cells in scleroderma and related fibrotic diseases. Current Opinion In Rheumatology 2024, 36: 379-386. PMID: 39171604, PMCID: PMC11451931, DOI: 10.1097/bor.0000000000001047.Peer-Reviewed Original ResearchScRNA-seqIdiopathic pulmonary fibrosisMyeloid cell typesScRNA-seq studiesScRNA-seq analysisSingle-cell RNA sequencingCell typesDendritic cellsFc receptor genesScleroderma skinExpression of EREGLung fibrosis severityFibrotic diseasesMyeloid cell populationsRNA sequencingMultiple tissuesSignaling mechanismsReceptor geneMyeloid cellsSSc skinPulmonary fibrosisFibrosis severityLung fibrosisCardiac fibrosisSPP1CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury
Shen S, Wang P, Wu P, Huang P, Chi T, Xu W, Xi Y. CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury. Molecular Therapy 2024, 32: 3974-3989. PMID: 39245939, PMCID: PMC11573616, DOI: 10.1016/j.ymthe.2024.09.008.Peer-Reviewed Original ResearchWnt/b-catenin signalingStem cell activityLung epitheliumAlveolar regenerationPulmonary fibrosisLung fibrosisWnt signalingCell activationMouse models of lung injuryModel of lung injuryWnt activityAlveolar type II cell proliferationBleomycin-induced injuryAmeliorated pulmonary fibrosisActivation of Wnt signalingType II cell proliferationInhibit lung fibrosisRegenerative medicineAnti-fibrotic effectsTreating pulmonary fibrosisActivated Wnt signalingLung injuryMouse modelFibrosisWnt/b-cateninRetraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Lee C, He C, Park J, Lee J, Kamle S, Ma B, Akosman B, Cortez R, Chen E, Zhou Y, Herzog E, Ryu C, Peng X, Rosas I, Poli S, Bostwick C, Choi A, Elias J, Lee C. Retraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Science Alliance 2024, 7: e202402987. PMID: 39209538, PMCID: PMC11361373, DOI: 10.26508/lsa.202402987.Peer-Reviewed Original Research
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