2022
A genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis
Franks JM, Toledo DM, Martyanov V, Wang Y, Huang S, Wood TA, Spino C, Chung L, Denton C, Derrett-Smith E, Gordon JK, Spiera R, Domsic R, Hinchcliff M, Khanna D, Whitfield ML. A genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis. Rheumatology 2022, 62: 19-28. PMID: 35751592, PMCID: PMC9788818, DOI: 10.1093/rheumatology/keac344.Peer-Reviewed Original ResearchConceptsMolecular subsetsIntrinsic subsetInflammatory subsetBaseline demographicsSSc patientsWhite/Caucasian patientsBaseline clinical demographicsAverage disease durationRodnan skin scoreAfrican American/BlackASSET trialUnique gene expression signatureDisease durationGene expression signaturesClinical demographicsParticipant seraSkin scoreSystemic sclerosisValidation cohortClinical variablesCaucasian patientsSpecific therapyAmerican/BlackSkin biopsiesDisease pathogenesis
2020
Profibrotic Activation of Human Macrophages in Systemic Sclerosis
Bhandari R, Ball MS, Martyanov V, Popovich D, Schaafsma E, Han S, ElTanbouly M, Orzechowski NM, Carns M, Arroyo E, Aren K, Hinchcliff M, Whitfield ML, Pioli PA. Profibrotic Activation of Human Macrophages in Systemic Sclerosis. Arthritis & Rheumatology 2020, 72: 1160-1169. PMID: 32134204, PMCID: PMC7329566, DOI: 10.1002/art.41243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, CDAntigens, Differentiation, MyelomonocyticCell DifferentiationChemokine CCL2Coculture TechniquesFemaleFibroblastsFibrosisHLA-DR AntigensHumansImmunophenotypingInterleukin-6Lectins, C-TypeLeukocytes, MononuclearMacrophage ActivationMacrophagesMaleMannose ReceptorMannose-Binding LectinsMiddle AgedMonocytesPhosphorylationReceptor, Transforming Growth Factor-beta Type IReceptor, Transforming Growth Factor-beta Type IIReceptors, Cell SurfaceRNA, MessengerScleroderma, SystemicSkinSTAT3 Transcription FactorTranscriptomeTransforming Growth Factor betaConceptsPeripheral blood mononuclear cellsSystemic sclerosisSSc patientsBasal conditionsSex-matched healthy controlsSSc fibroblastsSurface markersHealthy donor monocytesBlood mononuclear cellsMediator of fibrosisInflammatory macrophage activationMonocyte-derived macrophagesActivation profilesGrowth factor βFibrotic activationGene expression signaturesDonor monocytesMononuclear cellsProfibrotic activationSkin fibrosisInterleukin-6Healthy controlsSSc skinIndependent cohortMacrophage activation
2017
A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis
Taroni JN, Greene CS, Martyanov V, Wood TA, Christmann RB, Farber HW, Lafyatis RA, Denton CP, Hinchcliff ME, Pioli PA, Mahoney JM, Whitfield ML. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis. Genome Medicine 2017, 9: 27. PMID: 28330499, PMCID: PMC5363043, DOI: 10.1186/s13073-017-0417-1.Peer-Reviewed Original ResearchConceptsDisease-associated signaturesFunctional genomic networksGene expression signaturesPulmonary fibrosisAutoimmune diseasesDisease processMulti-organ autoimmune diseaseDistinct underlying pathologyPro-fibrotic macrophagesInternal organ involvementPulmonary arterial hypertensionExpression signaturesSkin of patientsInnate immune systemWilcoxon rank sum testGenomic networksRank sum testBackgroundSystemic sclerosisArterial hypertensionOrgan involvementSystemic sclerosisUnderlying pathologyLung microenvironmentSkin fibrosisFibrotic genes
2015
Experimentally-Derived Fibroblast Gene Signatures Identify Molecular Pathways Associated with Distinct Subsets of Systemic Sclerosis Patients in Three Independent Cohorts
Johnson ME, Mahoney JM, Taroni J, Sargent JL, Marmarelis E, Wu MR, Varga J, Hinchcliff ME, Whitfield ML. Experimentally-Derived Fibroblast Gene Signatures Identify Molecular Pathways Associated with Distinct Subsets of Systemic Sclerosis Patients in Three Independent Cohorts. PLOS ONE 2015, 10: e0114017. PMID: 25607805, PMCID: PMC4301872, DOI: 10.1371/journal.pone.0114017.Peer-Reviewed Original ResearchConceptsNormal-like subsetsGenome-wide expression profilingSet of genesDifferential gene expressionDistinct signaling pathwaysInflammatory subsetSystemic sclerosisGene signatureIndependent cohortGene expression signaturesLipid signalingInnate immune pathwaysActive TGFβ signalingExpression profilingSystemic sclerosis patientsMolecular relationshipsGene expressionNon-lesional skinTGFβ signalingSignaling pathwaysSubsets of diseaseMolecular pathwaysMicroarray datasetsExpression signaturesEarly disease pathologyMolecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures
Taroni JN, Martyanov V, Huang CC, Mahoney JM, Hirano I, Shetuni B, Yang GY, Brenner D, Jung B, Wood TA, Bhattacharyya S, Almagor O, Lee J, Sirajuddin A, Varga J, Chang RW, Whitfield ML, Hinchcliff M. Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures. Arthritis Research & Therapy 2015, 17: 194. PMID: 26220546, PMCID: PMC4518531, DOI: 10.1186/s13075-015-0695-1.Peer-Reviewed Original ResearchConceptsSystemic sclerosisEsophageal biopsiesInflammatory signatureLarge inflammatory infiltratesConsecutive SSc patientsSmooth muscle atrophyAbsence of fibrosisSmooth muscle functionProliferative gene expression signatureGene expression subsetsSmooth muscle cellsEsophageal dilatationGene expression signaturesSSc patientsEsophageal fibrosisSerum autoantibodiesInflammatory infiltrateEsophageal pathologyImmune activationAutopsy studySSc pathogenesisSSc casesMolecular subsetsGene expressionMuscle atrophy
2013
Molecular Signatures in Skin Associated with Clinical Improvement during Mycophenolate Treatment in Systemic Sclerosis
Hinchcliff M, Huang CC, Wood TA, Mahoney J, Martyanov V, Bhattacharyya S, Tamaki Z, Lee J, Carns M, Podlusky S, Sirajuddin A, Shah SJ, Chang RW, Lafyatis R, Varga J, Whitfield ML. Molecular Signatures in Skin Associated with Clinical Improvement during Mycophenolate Treatment in Systemic Sclerosis. Journal Of Investigative Dermatology 2013, 133: 1979-1989. PMID: 23677167, PMCID: PMC3714324, DOI: 10.1038/jid.2013.130.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiopsyCluster AnalysisFemaleGene Expression RegulationGenetic HeterogeneityGenetic MarkersHumansImmunosuppressive AgentsMaleMiddle AgedMycophenolic AcidPredictive Value of TestsReverse Transcriptase Polymerase Chain ReactionScleroderma, SystemicSkin Physiological PhenomenaTranscriptomeYoung AdultConceptsMRSS improvementSystemic sclerosisIntrinsic subsetMycophenolate mofetil treatmentCyclophosphamide-treated patientsGene expression changesGene expression subsetsMycophenolate treatmentTreatment biopsiesClinical improvementMMF treatmentMofetil treatmentGene expression signaturesSSc patientsSerial biopsiesClinical trialsExpression changesBaseline gene expressionGene expressionSSc skinSkin AssociatedPatientsTargeted treatmentPatient biopsiesBiopsy