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
IMPAIRED CORONARY FLOW RESERVE ON 82RUBIDIUM POSITRON EMISSION TOMOGRAPHY IMAGING PREDICTS ADVERSE EVENTS IN PATIENTS WITH AUTOIMMUNE DISEASE
Feher A, Boutagy N, Oikonomou E, Miller E, Sinusas A, Hinchcliff M. IMPAIRED CORONARY FLOW RESERVE ON 82RUBIDIUM POSITRON EMISSION TOMOGRAPHY IMAGING PREDICTS ADVERSE EVENTS IN PATIENTS WITH AUTOIMMUNE DISEASE. Journal Of The American College Of Cardiology 2020, 75: 1726. DOI: 10.1016/s0735-1097(20)32353-6.Peer-Reviewed Original Research
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
2016
Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity
Lofgren S, Hinchcliff M, Carns M, Wood T, Aren K, Arroyo E, Cheung P, Kuo A, Valenzuela A, Haemel A, Wolters PJ, Gordon J, Spiera R, Assassi S, Boin F, Chung L, Fiorentino D, Utz PJ, Whitfield ML, Khatri P. Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity. JCI Insight 2016, 1: e89073. PMID: 28018971, PMCID: PMC5161207, DOI: 10.1172/jci.insight.89073.Peer-Reviewed Original ResearchSSc patientsSystemic sclerosisDisease severityMulticohort analysisHealthy controlsHigh case fatality rateLarge longitudinal trialsSkin severity scoreUnmet critical needRare autoimmune diseaseMonths of treatmentRodnan skin scoreConnective tissue diseaseCase fatality rateSkin samplesPotential clinical utilitySkin biopsy samplesRobust molecular signatureSSc cohortSkin scoreTissue diseaseAutoimmune diseasesSeverity scorePatient responseDiscovery cohort
2014
FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling
Bhattacharyya S, Tamaki Z, Wang W, Hinchcliff M, Hoover P, Getsios S, White ES, Varga J. FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling. Science Translational Medicine 2014, 6: 232ra50. PMID: 24739758, PMCID: PMC4414050, DOI: 10.1126/scitranslmed.3008264.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Endogenous TLR4 ligandsCutaneous fibrosisTLR4 ligandToll-like receptor signalingProgressive autoimmune diseaseLesional skin biopsiesFibronectin extra domain ATreatment of fibrosisTissue repair responseHallmark of sclerodermaPersistent fibroblast activationExtra domain ATLR4 blockadeAutoimmune diseasesChronic conditionsChronic fibrosisReceptor 4Skin biopsiesFibrotic responseOrganotypic skin equivalentsMultiple organsPotent stimulusSclerodermaFibroblast activation
2011
Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps
Tan BK, Li QZ, Suh L, Kato A, Conley DB, Chandra RK, Zhou J, Norton J, Carter R, Hinchcliff M, Harris K, Peters A, Grammer LC, Kern RC, Mohan C, Schleimer RP. Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps. Journal Of Allergy And Clinical Immunology 2011, 128: 1198-1206.e1. PMID: 21996343, PMCID: PMC3384688, DOI: 10.1016/j.jaci.2011.08.037.Peer-Reviewed Original ResearchConceptsPresence of autoantibodiesChronic rhinosinusitisNasal polypsNasal tissueAnti-dsDNA antibody levelsSelf-reactive B cell clonesIgA-secreting plasma cellsB-cell activating factorControl nasal tissueEvidence of autoimmunityAnti-dsDNA IgGB cell clonesPotential of antibodiesAutoantibody microarrayAutoantibody levelsIgA antibodiesSpecific autoantibodiesAntibody levelsSubepithelial depositionAutoimmune diseasesSinonasal tissueControl subjectsInflammatory conditionsRevision surgeryImmunoglobulin production