grant
Crosstalk of Immune Dysregulation and Impaired Wound Healing in inherited STAT4-mediated Autoinflammatory Disease
Organization UNIVERSITY OF CALIFORNIA, SAN DIEGOLocation LA JOLLA, UNITED STATESPosted 1 Feb 2025Deadline 31 Jan 2030
NIHUS FederalResearch GrantFY2025AcLDLAffectAngiogenesis FactorAngiogenic FactorAssayAttentionB cell differentiation factorB cell stimulating factor 2B-Cell Differentiation FactorB-Cell Differentiation Factor-2B-Cell Stimulatory Factor-2BCDFBSF-2BSF2BioassayBiological AssayBleedingBlood VesselsBone MarrowBone Marrow Blood-Deriving CellBone Marrow Blood-Forming CellBone Marrow CellsBone Marrow Reticuloendothelial SystemCancersCell BodyCell Communication and SignalingCell FunctionCell PhysiologyCell ProcessCell SignalingCellsCellular FunctionCellular PhysiologyCellular ProcessCessation of lifeChemotactic CytokinesChildhoodChronicCompetenceCritical PathsCritical PathwaysCytoplasmCytotoxic cellDNA mutationDataDeathDeath RateDefectDevelopmentDiagnosisDisablingDiseaseDisease ProgressionDisorderEndothelial CellsExperimental ModelsFITC-dextranFailureFamilyFibroblastsGene TranscriptionGene variantGeneticGenetic ChangeGenetic PredispositionGenetic Predisposition to DiseaseGenetic SusceptibilityGenetic TranscriptionGenetic defectGenetic mutationGenetic propensityGenetic studyHPGFHematopoieticHemorrhageHepatocyte-Stimulating FactorHereditaryHomeHomologous Chemotactic CytokinesHumanHybridoma Growth FactorIFN-beta 2IFNB2IL-6IL6 ProteinImmuneImmunesImmunomodulationImpaired tissue repairImpaired wound healingIn VitroInflammationInflammatoryInheritedInherited PredispositionInherited SusceptibilityIntercrinesInterleukin-6Intracellular Communication and SignalingInvestigationInvestigatorsJointsJournalsK lymphocyteKnock-inLeadLifeLymphatic cellLymphocyteLymphocyticMGI-2MagazineMalignant NeoplasmsMalignant TumorMediatingMedicalMedicineMembraneMendelian diseaseMendelian disorderMendelian genetic disorderMiceMice MammalsModelingModern ManMolecularMorbidityMorbidity - disease rateMorpheaMucosaMucosal TissueMucous MembraneMurineMusMutationMyeloid Differentiation-Inducing ProteinNK CellsNatural Killer CellsNatureNew EnglandNon-Polyadenylated RNANortheastern United StatesOxidative StressOxidative Stress InductionPancytopeniaPathologicPathologyPathway interactionsPatientsPb elementPeripheralPermeabilityPhenotypePhosphorylationPlasmacytoma Growth FactorPrimary ImmunodeficiencyProductionProgenitor CellsProtein PhosphorylationProteomicsRNARNA ExpressionRNA Gene ProductsRNA SeqRNA sequencingRNAseqResearch PersonnelResearchersRibonucleic AcidRoleSIS cytokinesSTAT4STAT4 geneSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSkinSubcellular ProcessSymptomsSyndromeT-Cell DevelopmentT-Cell OntogenyT-Lymphocyte DevelopmentTestingTranscriptionUpregulationVariantVariationWound Repairabnormal tissue repairacetyl-LDLacetyl-low density lipoproteinsacetylated LDLacetylated low density lipoproteinallelic variantangiogenesisautoinflammationautoinflammatoryautoinflammatory diseasesautoinflammatory disordersautosomebiological signal transductionblood losschemoattractant cytokinechemokinecongenital immune deficiencycongenital immunodeficiencycutaneous fibrosiscytokinecytopeniadelayed wound healingdermal fibrosisdevelopmentalexhaustionfibrotic skinfluorescein isothiocyanate dextranfluoresceinthiocarbamoyl dextransgain of functiongain of function mutationgenetic etiologygenetic immune defectgenetic immune deficiencygenetic immunodeficiencygenetic mechanism of diseasegenetic variantgenetic vulnerabilitygenetically predisposedgenome mutationgenomic variantheavy metal Pbheavy metal leadhemopoietichomeshypogammaglobulinemiaiPSiPSCiPSCsimmune modulationimmune regulationimmunologic reactivity controlimmunomodulatoryimmunoregulationimmunoregulatoryimprovedin vivoinborn errors in immunityinborn errors of immunityinborn immunodeficiencyinduced pluripotent cellinduced pluripotent stem cellinduced pluripotent stem cells derived from patientsinduced pluripotent stem cells from patientsinducible pluripotent cellinducible pluripotent stem cellineffective therapiesineffective treatmentinfection recurrenceinherited immune defectinherited immune deficiencyinherited immunodeficiencyinhibitorinterferon beta 2knockinlymph cellmalignancymembrane structuremonogenic diseasemonogenic disordermortalitymortality ratemortality rationeoplasm/cancerneovascularizationnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapypathwaypatient derived human iPSpatient derived human iPSCpatient derived human induced pluripotent stem cellpatient derived iPSpatient derived iPSCpatient derived induced pluripotent cellspatient derived induced pluripotent stem cellspatient-derived pluripotent stem cellspediatricpharmacologicpreventpreventingprimary immune defectprimary immune deficiencyprogenitorrecurrent infectionrecurring infectionsingle-gene diseasesingle-gene disorderskin fibrosissocial rolestem cellssystemic inflammationsystemic inflammatory responsetherapeutic targettissue woundtranscriptome sequencingtranscriptomic sequencingtranscriptomicsuptakevascularwoundwound healingwound recoverywound resolutionwoundingwounds
Description preview
Abstract
Disabling pansclerotic morphea (DPM) is a severe, systemic disorder of childhood with debilitating skin, joint,
and mucosal symptoms, immune dysregulation and malignancy. DPM is known to be severely recalcitrant to
therapy, leading to death within 10 years of diagnosis. Our investigation of the specific contribution of STAT4 to
the…
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