grant
Interferon Regulatory Factor 7 Links Interferon Pathway Activation to the Exaggerates Fibrotic Response in Systemic Sclerosis
Organization UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTONLocation HOUSTON, UNITED STATESPosted 1 May 2023Deadline 30 Apr 2028
NIHUS FederalResearch GrantFY2026AddressAttenuatedAutoimmuneAutoimmune DiseasesBasal Transcription FactorBasal transcription factor genesBleoBleomycinBloodBlood CellsBlood Reticuloendothelial SystemBody TissuesBone-Derived Transforming Growth FactorCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCas nuclease technologyCell Communication and SignalingCell LineCell SignalingCellLineChIP SequencingChIP-seqChIPseqClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyDataDermalDevelopmentDiseaseDisorderEffector CellExpression SignatureFibroblastsFibrosisGene Action RegulationGene ExpressionGene Expression MonitoringGene Expression Pattern AnalysisGene Expression ProfileGene Expression ProfilingGene Expression RegulationGene RegulationGene Regulation ProcessGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGenetic PredispositionGenetic Predisposition to DiseaseGenetic SusceptibilityGenetic TranscriptionGenetic propensityGoalsHumanIFNIRF-7 proteinImmuneImmune systemImmunesImmunityIn VitroIn-bleomycinInherited PredispositionInherited SusceptibilityInterferon Type IInterferonsIntracellular Communication and SignalingJV15-2KO miceKnock-out MiceKnockout MiceLinkLong-term cohortLongitudinal cohortMADH3MADH3 geneMediatingMiceMice MammalsMilk Growth FactorModelingModern ManMolecularMolecular FingerprintingMolecular ProfilingMorbidityMothers Against Decapentaplegic, Drosophila, Homolog of, 3MurineMusMusculoskeletal Pain DisorderNon-Polyadenylated RNANull MouseOrganPathogenesisPathologicPathway interactionsPatientsPeripheral Blood CellPlatelet Transforming Growth FactorPublishingRNARNA ExpressionRNA Gene ProductsRNA SeqRNA sequencingRNAseqRheumatic DiseasesRheumatismRheumatologic DiseasesRheumatologic DisorderRibonucleic AcidRoleSMA- and MAD-Related Protein 3SMAD3SamplingSclerodermaSignal TransductionSignal Transduction SystemsSignalingSingle Base PolymorphismSingle Nucleotide PolymorphismSkinSkin TissueStrains Cell LinesSystemSystemic SclerodermaSystemic SclerosisTGF BTGF-betaTGF-βTGFbetaTGFβTissuesTranscriptTranscript Expression AnalysesTranscript Expression AnalysisTranscriptionTranscription Factor Proto-OncogeneTranscription factor genesTransforming Growth Factor betaTransforming Growth Factor-Beta Family GeneUpregulationWorkanalyze gene expressionattenuateattenuatesautoimmune conditionautoimmune disorderautoimmunity diseasebiological signal transductionchromatin immunoprecipitation coupled with sequencingchromatin immunoprecipitation followed by sequencingchromatin immunoprecipitation with sequencingchromatin immunoprecipitation-seqchromatin immunoprecipitation-sequencingconditional knock-outconditional knockoutcultured cell linecutaneous fibrosiscutaneous tissuedermal fibrosisdermatosclerosisdevelopmentaleffective therapyeffective treatmentexperimentexperimental researchexperimental studyexperimentsfibrotic skingene expression analysisgene expression assaygene expression patterngene expression signaturegenetic vulnerabilitygenetically predisposedin vivoindium-bleomycininsightinterferon regulatory factor-7knock-downknockdownmolecular profilemolecular signaturemortalitymouse modelmurine modeloverexpressoverexpressionpathwayperipheral bloodprogressive systemic sclerosisresponsescRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle nucleotide variantsingle-cell RNA sequencingskin fibrosissocial roletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttranscription factortranscriptional profiletranscriptional profilingtranscriptional signaturetranscriptome sequencingtranscriptomic sequencing
Description preview
Systemic sclerosis (SSc-scleroderma) is a multisystem autoimmune, fibrotic disease associated with high
morbidity and mortality. Progress in the development of effective therapies for SSc has been hampered by a
fragmented understanding of its pathogenesis. Although abundant evidence implicates dysregulated immunity
in SSc, the mechanisms by which…
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