grant
Gene regulation mechanisms involving the inactive X in B cells during lupus disease
Organization UNIVERSITY OF PENNSYLVANIALocation PHILADELPHIA, UNITED STATESPosted 1 Jun 2018Deadline 31 Aug 2030
NIHUS FederalResearch GrantFY20253-D3-Dimensional3DAccelerationAgonistAldaraAllelesAllelomorphsAlpha-Beta-Omega Interferon Receptor-1Antiviral Protein Alpha TypeArchitectureAutoantibodiesAutoimmune DiseasesAutoimmune StatusAutoimmunityAutomobile DrivingB blood cellsB cellB cellsB-Cell ActivationB-Cell SubsetsB-CellsB-Lymphocyte SubsetsB-LymphocytesB-cellBlood Plasma CellCD11cCD4 CellsCD4 Positive T LymphocytesCD4 T cellsCD4 helper T cellCD4 lymphocyteCD4+ T-LymphocyteCD4-Positive LymphocytesCLGICUT&RUNCell BodyCell Communication and SignalingCell SignalingCellsCharacteristicsChromosomesChronicCleavage Targets and Release Using NucleaseCleavage Under Targets and Release Using NucleaseDNADataDeoxyribonucleic AcidDevelopmentDifferential Gene ExpressionDiseaseDisease ProgressionDisorderDisproportionate number of femalesDisproportionate number of womenDisproportionately affects femalesDisproportionately affects womenDisproportionately impacts femalesDisproportionately impacts womenDisproportionately in femalesDisproportionately in womenDouble-Stranded DNAEngineering / ArchitectureEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessExhibitsFemaleFishesFutureGender BiasGene Action RegulationGene Copy NumberGene DosageGene ExpressionGene Expression RegulationGene InactivationGene RegulationGene Regulation ProcessGene SilencingGene TranscriptionGenesGeneticGenetic TranscriptionGerminal CenterHi-CHistonesHuIFN-Alpha-RecHumanIFNIFNBRIFRCIRAKIRAK1IRAK1 geneITGAXITGAX geneImageImiquimodImmune systemImmunityImpairmentIn VitroInflammationInjectionsInterferon Alpha-Beta Receptor Alpha ChainInterferon ReceptorInterferon Type IInterferonsInterleukin-1 Receptor-Associated Kinase 1Intracellular Communication and SignalingLinkLupusLupus Erythematosus DisseminatusLymphatic cellLymphocyteLymphocyticLyonizationMaintenanceMiceMice MammalsModern ManModificationMolecularMurineMusNon-Polyadenylated RNAPathway interactionsPatientsPatternPlasma CellsPlasmacytesPredisposition genePristaneProductionPromoter RegionsPromotor RegionsRNARNA ExpressionRNA Gene ProductsRNA SeqRNA sequencingRNAseqReceptor SignalingRibonucleic AcidSLESex BiasSignal TransductionSignal Transduction SystemsSignalingSomatic CellStructure of germinal center of lymph nodeSusceptibility GeneSystemic Lupus ErythematosusSystemic Lupus ErythematousSystemic Lupus ErythmatosusT4 CellsT4 LymphocytesTIMP1TIMP1 geneTLR7TLR7 geneTestingTherapeutic InterventionTissue-Specific Differential Gene ExpressionTissue-Specific Gene ExpressionToll-Like Receptor 7TranscriptionX ChromosomeX InactivationX-Chromosome Inactivationactivated B cellsage associatedage correlatedage dependentage linkedage relatedage specificautoimmune antibodyautoimmune conditionautoimmune disorderautoimmunity diseaseautoreactive antibodybiological signal transductiondevelopmentaldisease modeldisorder modeldisseminated lupus erythematosusdrivingds-DNAdsDNAepigeneticallyepigenomicsfemale biasfemale predominancefemale preponderancegene signaturesgenetic promoter elementgenetic promoter sequencegenetic signaturehistone modificationifnar1 gene productimaginginnovateinnovationinnovativeinsightintervention therapylupus-likelymph cellmalemouse modelmurine modelnew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetoverexpressoverexpressionpathwaypelleplasmocytepleiotropic effectpleiotropismpleiotropypredisposing genepredominance in femalespredominance in womenpromoterpromoter sequencepromotorscRNA sequencingscRNA-seqself reactive antibodysingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsusceptibility allelesusceptibility locussusceptibility variantsystemic lupus erythematosisthree dimensionaltranscriptional silencingtranscriptome sequencingtranscriptomic sequencingtype I IFN receptortype I interferon receptorwomen's predominancewomen's preponderance♀♂
Description preview
Females are predisposed for developing systemic lupus erythematosus (SLE), but the underlying mechanisms
remain obscure. Chronic inflammation is also a feature of SLE, and the majority of SLE patients have elevated
type I interferon (IFN) levels and increased expression of interferon signature genes. B cells from female SLE
patients exhibit…
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