grant
Activating Autophagy to Treat Uromodulin-Associated Genetic Chronic Kidney Disease
Organization WASHINGTON UNIVERSITYLocation SAINT LOUIS, UNITED STATESPosted 15 Aug 2017Deadline 31 Aug 2029
NIHUS FederalResearch GrantFY2025ATF6ATF6 geneAblationAccelerationActivating Transcription Factor 6Active OxygenAddressAdeno-Associated VirusesApoptosisApoptosis PathwayAstrocytesAstrocytusAstrogliaAutophagocytosisBiologicalBiological Response Modifier TherapyBiological TherapyBiologyBlood SerumCRE RecombinaseCRISPRCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas systemCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCas nuclease technologyCell BodyCell Communication and SignalingCell DeathCell SignalingCell modelCellsCellular modelCessation of lifeChronic Kidney FailureChronic Renal DiseaseChronic Renal FailureClinicalClustered Regularly Interspaced Short Palindromic RepeatsClustered 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 technologyDNA mutationDeathDeletion MutationDependoparvovirusDependovirusDiseaseDisease ProgressionDisorderER stressEndoplasmic ReticulumEnterobacteria phage P1 Cre recombinaseEpithelial CellsErgastoplasmExtravasationExtremitiesFKHR-Like 1FKHRL1FOXO3FOXO3AFOXO3A geneFibrosisForkhead Box O3AForkhead in Rhabdomyosarcoma-Like 1Gene TranscriptionGeneticGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGoalsHereditaryHumanImageImmuneImmune signalingImmunesImpairmentIn SituInflammationInheritedInjuryIntracellular Communication and SignalingInvestigatorsKO miceKidneyKidney DiseasesKidney FailureKidney InsufficiencyKidney Urinary SystemKnock-outKnock-out MiceKnockoutKnockout MiceLeakageLegal patentLimb structureLimbsLinkLoxP-flanked alleleMediatingMedicalMiceMice MammalsMitochondriaMitochondrial DNAModelingModern ManMolecularMurineMusMutationNGF ReceptorsNephropathyNerve Growth Factor ReceptorsNeurotrophic Factor ReceptorNeurotrophin ReceptorsNon-Polyadenylated RNANon-TrunkNull MouseOnset of illnessOrganellesOxygen RadicalsPET/CTPET/CT scanPatentsPathogenesisPatientsPositionPositioning AttributePro-OxidantsProgrammed Cell DeathProteinsRNARNA ExpressionRNA Gene ProductsReactive Oxygen SpeciesReceptor ProteinRegulationRenal DiseaseRenal FailureRenal InsufficiencyRenal functionResearchResearch PersonnelResearchersRibonucleic AcidRoleSerumSignal TransductionSignal Transduction SystemsSignalingSignaling MoleculeSpillageStimulator of Interferon GenesTHGPTHP geneTHP proteinTestingTherapeuticThickThicknessTranscriptionTransgenic MiceTubularTubular formationUMODUMOD geneUpregulationValidationadeno associated virus groupastrocytic gliaattenuationautophagyautosomebacteriophage P1 recombinase Crebiologicbiological signal transductionbiological therapeuticbiological treatmentbiologically based therapeuticsbiotherapeuticsbiotherapycGAMP STINGcGAMP-STINGcGAMP/STINGcGAS/STINGcausal allelecausal genecausal mutationcausal variantcausative mutationcausative variantchronic kidney diseaseclinical translationclinically translatableconditional knock-outconditional knockoutcyclic GMP-AMP synthase/STINGdisease onsetdisorder onsetendoplasmic reticulum stressfloxedfloxed allelegenome mutationimagingimaging detectionimaging-based detectionimaging-based disease detectionimprovedin vivoinjuriesinnovateinnovationinnovativeinnovative technologiesinsightinterestkidney disorderkidney fibrosiskidney functionmitochondrialmouse modelmtDNAmurine modelmutantnecrocytosisneurotrophic factorneurotrophinneutrophinnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynovelnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachoverexpressoverexpressionpositron emission computed tomographyreceptorrenalrenal disorderrenal fibrosisscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial rolespatial RNA sequencingspatial gene expression analysisspatial gene expression profilingspatial resolved transcriptome sequencingspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatially resolved transcriptomicsspatio transcriptomicstargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttooluromodulinvalidations
Description preview
Uromodulin-associated genetic chronic kidney disease, or autosomal dominant tubulointerstitial kidney disease
caused by uromodulin mutations (ADTKD-UMOD), is a leading hereditary kidney disease and characterized by
renal fibrosis and progressive loss of kidney function. Currently there is no targeted therapy. To address the
unmet medical needs, by…
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