2024
Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease
Yang M, Lee S, Neely J, Hinchcliff M, Wolters P, Sirota M. Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease. Frontiers In Immunology 2024, 15: 1326922. PMID: 38348044, PMCID: PMC10859856, DOI: 10.3389/fimmu.2024.1326922.Peer-Reviewed Original ResearchConceptsScleroderma-associated interstitial lung diseaseSSc-ILDInterstitial lung diseaseLung tissueGene expression meta-analysisPulmonary fibrosisLung diseaseSenescence signatureDegree of skin involvementIdiopathic pulmonary fibrosisTelomere lengthType II alveolar cellsCellular senescence signaturesCellular senescenceIndependent of ageSkin involvementSSc skinExpression meta-analysisHealthy controlsAssociated with degreeAlveolar cellsLungMeta-analysisAging genesFibrosis
2022
Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis
Odell I, Steach H, Gauld S, Reinke-Breen L, Karman J, Carr T, Wetter J, Phillips L, Hinchcliff M, Flavell R. Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis. Science Immunology 2022, 7: eabq6691. PMID: 36490328, PMCID: PMC9840167, DOI: 10.1126/sciimmunol.abq6691.Peer-Reviewed Original ResearchConceptsLung fibrosisDendritic cellsImmune cellsDiffuse cutaneous systemic sclerosisPersistence of fibrosisCutaneous systemic sclerosisExtent of fibrosisType I interferonSystemic sclerosisAutoimmune diseasesAntifibrotic targetsTherapeutic administrationMouse modelI interferonLung samplesLung explantsFibrosisFibrotic tissueImmune signalsEpiregulin expressionPatient's skinExtracellular matrix productionGenetic deficiencyEpiregulinEGFR ligands
2020
Current and Potential New Targets in Systemic Sclerosis Therapy: a New Hope
Hinchcliff M, O’Reilly S. Current and Potential New Targets in Systemic Sclerosis Therapy: a New Hope. Current Rheumatology Reports 2020, 22: 42. PMID: 32562016, PMCID: PMC7305248, DOI: 10.1007/s11926-020-00918-3.Peer-Reviewed Original ResearchConceptsSkin fibrosisNew targetsSSc interstitial lung diseaseAutoimmune connective tissue diseaseSystemic sclerosis therapyConnective tissue diseaseInterstitial lung diseaseCurrent ongoing trialsNew therapeutic targetsActivation of fibroblastsPotential new targetsReviewSystemic sclerosisSclerosis therapyOngoing trialsTissue diseaseLung diseaseClinical trialsTherapeutic targetRate of declineDisease pathogenesisPhase IIIPhase IIFibrosisNew hopeDiseasePro-fibrotic Activation of Human Macrophages in Systemic Sclerosis
Bhandari R, Ball M, Martyanov V, Popovich D, Schaafsma E, Han S, Eltanbouly M, Carns M, Arroyo E, Aren K, Hinchcliff M, Whitfield M, Pioli P. Pro-fibrotic Activation of Human Macrophages in Systemic Sclerosis. The Journal Of Immunology 2020, 204: 224.33-224.33. DOI: 10.4049/jimmunol.204.supp.224.33.Peer-Reviewed Original ResearchSystemic sclerosisSSc patientsIL-6IL-6 blockadeHealthy donor monocytesMediator of fibrosisFibrotic activationSSc tissuesInflammatory signatureDonor monocytesPatient macrophagesHealthy donorsTherapeutic targetingBasal conditionsSoluble factorsHuman macrophagesSurface markersMacrophagesPatient's skinElevated levelsGene expression profilesSclerosisPatientsFibrosisImmunophenotypeCirculating classical monocytes share a common transcriptional signature with skin macrophages in Systemic Sclerosis
Makinde H, Dominguez S, Cuda C, Gadhvi G, Aren K, Zeng C, Eickelberg G, Khanna D, Assassi S, Frech T, Winter D, Perlman H, Hinchcliff M. Circulating classical monocytes share a common transcriptional signature with skin macrophages in Systemic Sclerosis. The Journal Of Immunology 2020, 204: 152.12-152.12. DOI: 10.4049/jimmunol.204.supp.152.12.Peer-Reviewed Original ResearchClassical monocytesSSc patientsSystemic sclerosisSkin macrophagesCommon transcriptional signatureEnd-organ fibrosisSystemic sclerosis cohortTranscriptional signatureSites of fibrosisPrecursors of macrophagesUpregulated genesSSc progressionProspective registryControl patientsProinflammatory moleculesSkin biopsiesPatientsMacrophage clustersMacrophagesMonocytesRespective controlsPrecursor populationSclerosisSignificant differencesFibrosis
2018
Diffuse cardiac fibrosis quantification in early systemic sclerosis by magnetic resonance imaging and correlation with skin fibrosis
Lee DC, Hinchcliff ME, Sarnari R, Stark MM, Lee J, Koloms K, Hoffmann A, Carns M, Thakrar A, Aren K, Varga J, Aquino A, Carr JC, Benefield BC, Shah SJ. Diffuse cardiac fibrosis quantification in early systemic sclerosis by magnetic resonance imaging and correlation with skin fibrosis. Journal Of Scleroderma And Related Disorders 2018, 3: 159-169. PMID: 29808171, PMCID: PMC5969530, DOI: 10.1177/2397198318762888.Peer-Reviewed Original ResearchEarly systemic sclerosisT1 mapping parametersSystemic sclerosisSSc patientsDiffuse myocardial fibrosisT1 mapping indicesSkin scoreMyocardial fibrosisSkin fibrosisCardiac structure/functionRodnan skin scoreCardiac magnetic resonance T1 mappingT1 mappingMagnetic resonance imagingMagnetic resonance T1 mappingCardiac involvementCardiovascular evaluationConsecutive patientsClinical studiesPatientsResonance imagingFibrosisFibrosis quantificationCine imagingSclerosis
2016
Tenascin-C drives persistence of organ fibrosis
Bhattacharyya S, Wang W, Morales-Nebreda L, Feng G, Wu M, Zhou X, Lafyatis R, Lee J, Hinchcliff M, Feghali-Bostwick C, Lakota K, Budinger GR, Raparia K, Tamaki Z, Varga J. Tenascin-C drives persistence of organ fibrosis. Nature Communications 2016, 7: 11703. PMID: 27256716, PMCID: PMC4895803, DOI: 10.1038/ncomms11703.Peer-Reviewed Original ResearchConceptsSystemic sclerosisToll-like receptorsOrgan fibrosisFibrosis resolutionPathogenesis of SScTreatment of SScLevels of tenascinEndogenous danger signalsSSc skin biopsy samplesSkin biopsy samplesMechanism of actionLung fibrosisPathogenic roleTLR activatorsMouse modelBiopsy samplesFibroblast activationDanger signalsMyofibroblast transformationFibrosisSSc fibroblastsCollagen gene expressionSkin fibroblastsAmplification loopTenascin
2013
Assessment of diffuse myocardial fibrosis in systemic sclerosis by cardiac magnetic resonance imaging
Lee D, Sarnari R, Benefield B, Aquino A, Carr J, Varga J, Hinchcliff M, Wu E, Shah S. Assessment of diffuse myocardial fibrosis in systemic sclerosis by cardiac magnetic resonance imaging. Journal Of Cardiovascular Magnetic Resonance 2013, 15: e121. PMCID: PMC3559286, DOI: 10.1186/1532-429x-15-s1-e121.Peer-Reviewed Original Research
2012
Imatinib mesylate causes genome-wide transcriptional changes in systemic sclerosis fibroblasts in vitro.
Hinchcliff M, Huang CC, Ishida W, Fang F, Lee J, Jafari N, Wilkes M, Bhattacharyya S, Leof E, Varga J. Imatinib mesylate causes genome-wide transcriptional changes in systemic sclerosis fibroblasts in vitro. Clinical And Experimental Rheumatology 2012, 30: s86-96. PMID: 22691216, PMCID: PMC3860597.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBiopsyCase-Control StudiesCells, CulturedFibroblastsFibrosisGene Expression ProfilingGene Expression RegulationHumansImatinib MesylateMiceMice, KnockoutOligonucleotide Array Sequence AnalysisPhosphorylationPiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-ablPyrimidinesScleroderma, SystemicSignal TransductionSkinTime FactorsTranscription, GeneticTransforming Growth Factor beta1ConceptsSystemic sclerosisSSc fibroblastsSkin biopsiesInternal organ fibrosisHeterogeneous multifactorial diseaseControl fibroblastsControl skin biopsiesFibrotic gene expressionSystemic sclerosis fibroblastsC-AblProgressive skinAntifibrotic effectsImatinib mesylateHealthy controlsCardiovascular diseaseGene expressionHealthy subjectsFibrotic responseCholesterol metabolismOrgan fibrosisC-Abl activationMultifactorial diseaseTreatment resultsTissue levelsFibrosis