2020
Regulator combinations identify systemic sclerosis patients with more severe disease
Wang Y, Franks JM, Yang M, Toledo DM, Wood TA, Hinchcliff M, Whitfield ML. Regulator combinations identify systemic sclerosis patients with more severe disease. JCI Insight 2020, 5: e137567. PMID: 32721949, PMCID: PMC7526449, DOI: 10.1172/jci.insight.137567.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseSystemic sclerosisActivity scoreSevere diseaseSevere interstitial lung diseaseSubsets of SScVital capacity declineRodnan skin scoreSubgroup of patientsSystemic sclerosis patientsHeterogeneous autoimmune disorderInternal organ dysfunctionGene expression subsetsSkin gene expressionActivation of regulatorsIntrinsic subsetOrgan dysfunctionSclerosis patientsSkin scoreAutoantibody productionClinical outcomesAutoimmune disordersClinical variablesLung diseaseSkin fibrosis
2016
Molecular Stratification by Gene Expression as a Paradigm for Precision Medicine in Systemic Sclerosis
Hinchcliff M, Whitfield M. Molecular Stratification by Gene Expression as a Paradigm for Precision Medicine in Systemic Sclerosis. 2016, 657-670. DOI: 10.1007/978-3-319-31407-5_49.Peer-Reviewed Original ResearchSystemic sclerosisPatient subsetsProgressive interstitial lung diseaseDiffuse cutaneous systemic sclerosisAppropriate patient subsetsScleroderma renal crisisCutaneous systemic sclerosisInvestigator-initiated trialPulmonary arterial hypertensionSubset of patientsDifferent patient subsetsInterstitial lung diseaseDifferent pathophysiological processesMolecular pathwaysPrecision medicineGene expression subsetsT lymphocyte activationUninvolved skin samplesInflammatory subsetRenal crisisSSc complicationsArterial hypertensionMycophenolate mofetilClinical improvementOrgan involvement
2015
Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms
Mahoney JM, Taroni J, Martyanov V, Wood TA, Greene CS, Pioli PA, Hinchcliff ME, Whitfield ML. Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms. PLOS Computational Biology 2015, 11: e1004005. PMID: 25569146, PMCID: PMC4288710, DOI: 10.1371/journal.pcbi.1004005.Peer-Reviewed Original ResearchConceptsGene-gene interaction networksGenetic risk lociInteraction networksGenome-wide gene expression datasetsRisk lociGene expression modulesSubset-specific genesExtracellular matrix remodelingGene expression datasetsExpression modulesSystemic sclerosisGene expressionGenetic polymorphismsIntrinsic subsetGenesSystem-level analysisExpression datasetsMatrix remodelingPolymorphic genesAntigen geneCell proliferationMultiple clinical cohortsOrgan fibrosisGene expression subsetsLociMolecular 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