grant
Investigating the role of A20 and DREAM in adipogenesis and systemic sclerosis
Organization UNIVERSITY OF MICHIGAN AT ANN ARBORLocation ANN ARBOR, UNITED STATESPosted 19 Sept 2025Deadline 31 Aug 2030
NIHUS FederalResearch GrantFY2025APF-1ATP-Dependent Proteolysis Factor 1AdipocytesAdipose CellAdipose tissueAnimal ModelAnimal Models and Related StudiesAnimalsAnti-diabetic AgentsAnti-diabetic DrugsAtrophicAtrophyAutoimmune DiseasesBindingBlood VesselsBody TissuesBone-Derived Transforming Growth FactorCell DifferentiationCell Differentiation processCell NucleusCell-Extracellular MatrixCharacteristicsClinicalCompetitive BindingCoriumCutaneous sclerosisCutisDNADNA BindingDNA Binding InteractionDNA boundData SetDeoxyribonucleic AcidDermalDermatologic biopsyDermisDevelopmentDiseaseDisorderDown-RegulationECMElementsEndothelial CellsEndotheliumEnzyme GeneEnzymesEquilibriumExpression SignatureExtracellular MatrixFDA approvedFat CellsFat progenitor cellFat stem cellFatty TissueFibroblastsFibrosisGene Expression ProfileGene TranscriptionGenesGenetic TranscriptionHMG-20High Mobility Protein 20HumanImmune responseImmunochemical ImmunologicImmunologicImmunologicalImmunologicallyImmunologicsIn VitroLipocytesLungLung Respiratory SystemMature LipocyteMature fat cellMediatorMesenchymalMesenchymal DifferentiationMesenchymal Progenitor CellMesenchymal Stem CellsMesenchymal progenitorMesenchymal stromal/stem cellsMiceMice MammalsMilk Growth FactorModelingModern ManMolecular InteractionMorphologyMurineMusMyofibroblastNatureNucleusOrganPathogenesisPathogenicityPathway interactionsPatientsPhenotypePlatelet Transforming Growth FactorPredisposition geneProcessPublicationsRNA ExpressionRegulationRegulatory ElementRepressionResolutionRoleScientific PublicationSclerodermaSkinSkin TissueSusceptibility GeneSystemic SclerodermaSystemic SclerosisTGF BTGF-betaTGF-βTGFbetaTGFβTissuesTranscriptionTranscription RepressorTranscriptional RepressorTransforming Growth Factor betaTransforming Growth Factor-Beta Family GeneUbiquitinVascular DiseasesVascular Disorderadipocyte developmentadipocyte differentiationadipocyte progenitorsadipocyte stem celladipocyte-derived stem celladipogenesisadiposeadipose derived stem celladipose progenitoradipose stem celladipose tissue derived stem celladipose tissue stem cellsantagonismantagonistanti-diabeticattenuationautoimmune conditionautoimmune disorderautoimmunity diseasebalancebalance functionblood vessel disordercell transformationcell typecellular differentiationcompetitively boundcutaneous biopsycutaneous fibrosiscutaneous tissuederepressiondermal fibrosisdermal sclerosisdermatosclerosisdevelopmentaleffective therapyeffective treatmentexperimentexperimental researchexperimental studyexperimentsfat derived stem cellfibrotic skingene expression patterngene expression signaturegene signaturesgenetic approachgenetic repressorgenetic signaturegenetic strategyglobal gene expressionglobal transcription profilehost responseimmune system responseimmunoresponseinhibitorinjury to the vasculatureinnovateinnovationinnovativelipid biosynthesislipogenesisloss of functionmesenchymal stromal cellmesenchymal stromal progenitor cellsmesenchymal-derived stem cellsmodel of animalmortalitynew approachesnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynovelnovel approachesnovel strategiesnovel strategynovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachpathwaypharmacologicpredisposing geneprogressive systemic sclerosispromoterpromotorrandomized, clinical trialsreconstitutereconstitutionrepaglinideresolutionsrestraintscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell technologysingle cell transcriptomic profilingsingle-cell RNA sequencingskin biopsyskin fibrosisskin sclerosissocial rolespatial RNA sequencingspatial gene expression analysisspatial gene expression profilingspatial resolved transcriptome sequencingspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatially resolved transcriptomicsspatio transcriptomicssusceptibility allelesusceptibility locussusceptibility varianttranscriptional profiletranscriptional signaturetranscriptometransdifferentiationtransformed cellstreatment strategyvascularvascular dysfunctionvascular injuryvasculopathywhite adipose tissueyellow adipose tissue
Description preview
PROJECT SUMMARY
The pathogenesis of systemic sclerosis (SSc) is not well understood, and effective treatments are lacking. A
unifying fibrosis paradigm is myofibroblast plasticity, by which quiescent resident myofibroblasts transform into
activated myofibroblasts during fibrosis development. Key interactions between vascular changes and early…
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