grant
Identifying and characterizing new therapy targets in TDP-43 proteinopathies
Organization WASHINGTON UNIVERSITYLocation SAINT LOUIS, UNITED STATESPosted 1 Mar 2026Deadline 28 Feb 2029
NIHUS FederalResearch GrantFY20263' Untranslated Regions3'UTRAD dementiaAD patientsALS patientsAddressAffectAgeAge related pathologiesAlternate SplicingAlternative RNA SplicingAlternative SplicingAlzheimer Type DementiaAlzheimer disease dementiaAlzheimer sclerosisAlzheimer syndromeAlzheimer'sAlzheimer's DiseaseAlzheimer's disease patientAlzheimer's patientAlzheimers DementiaAmentiaAmyotrophic Lateral SclerosisAmyotrophic Lateral Sclerosis Motor Neuron DiseaseAmyotrophic Lateral Sclerosis patientsAmyotrophic lateral sclerosis and frontotemporal degenerationAmyotrophic lateral sclerosis and frontotemporal dementiaAutopsyBindingBiologic ModelsBiological FunctionBiological ModelsBiological ProcessBiologyBody TissuesBrainBrain Nervous SystemBrain regionCRISPR activationCRISPR activatorCRISPR approachCRISPR based activationCRISPR based approachCRISPR gene activationCRISPR interferenceCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR transcription activationCRISPR transcriptional activationCRISPR-CAS-9CRISPR-Cas-9-mediated gene activationCRISPR-based gene activationCRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR-dCAS9 ActivatorCRISPR-dCas9-mediated repressionCRISPR-mediated transcriptional activationCRISPR/CAS approachCRISPR/CAS9 activationCRISPR/CAS9 gene activationCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCRISPR/dCas9 activationCRISPR/dCas9 interferenceCRISPR/dCas9-based transcriptional activationCRISPR/dCas9-mediated transcriptional inhibitionCRISPRaCRISPRiCas nuclease technologyCausalityCell Communication and SignalingCell SignalingClinicalClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats interferenceClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCognitive DisturbanceCognitive ImpairmentCognitive declineCognitive function abnormalCommunitiesComplexCytoplasmDataData SetDegenerative Neurologic DisordersDementiaDevelopmentDiseaseDisease ProgressionDisorderDisturbance in cognitionDysfunctionEncephalonEnvironmental FactorEnvironmental Risk FactorEtiologyEventExhibitsFTD dementiaFTD/ALSFTLD/ALSFrontal Temporal DementiaFrontotemporal DementiaFrontotemporal Lobar Degeneration/Amyotrophic lateral sclerosisFunctional RNAFunctional disorderGehrig's DiseaseGene TranscriptionGene variantGenesGeneticGenetic TranscriptionGenetic predisposing factorHealthHumanImmune PrecipitationImmunoprecipitationImpaired cognitionIndividualInduced pluripotent stem cell derived human neuronInduced pluripotent stem cell derived neuronsIntermediary MetabolismIntracellular Communication and SignalingIsoformsKnowledgeLengthLightLinkLou Gehrig DiseaseMJD1 proteinMT-bound tauMediatingMetabolic ProcessesMetabolismModel SystemModern ManMolecular InteractionMorbidityNerve CellsNerve DegenerationNerve UnitNervous System Degenerative DiseasesNeural CellNeural Degenerative DiseasesNeural degenerative DisordersNeurocyteNeurodegenerative DiseasesNeurodegenerative DisordersNeurologic Degenerative ConditionsNeuron DegenerationNeuron from iPSCNeuron from induced pluripotent stem cellsNeuronsNon-Polyadenylated RNANoncoding RNANontranslated RNANuclearNuclear ExportPathologicPathologyPathway interactionsPatientsPhosphorylationPhotoradiationPhysiopathologyPoly APoly(rA)PolyadenylationPopulationPost-Transcriptional ControlPost-Transcriptional Gene SilencingPost-Transcriptional RegulationPrimary Senile Degenerative DementiaProcessProtein IsoformsProtein PhosphorylationProteinsPublishingRNARNA ExpressionRNA Gene ProductsRNA InterferenceRNA PolyadenylationRNA ProcessingRNA SeqRNA SilencingRNA SplicingRNA metabolismRNA sequencingRNA-Binding ProteinsRNAiRNAseqRegulationResearchRibonucleic AcidRoleSCA3Sequence-Specific Posttranscriptional Gene SilencingSignal TransductionSignal Transduction SystemsSignalingSplicingStressSymptomsSystemTAR DNA binding protein 43 kDa pathologyTAR DNA binding protein 43 pathologyTAR DNA binding protein of 43 proteinopathyTAR DNA-binding protein 43TDP-43TDP43TDP43 associated neurodegenerationTDP43 associated neurodegenerative diseaseTDP43 associated pathologiesTDP43 induced neurodegenerationTDP43 neurodegenerationTDP43 neurodegenerative diseaseTDP43 neuropathologyTDP43 pathogenesisTDP43 pathologyTDP43 proteinopathyTDP43 related neurodegenerationTDP43 related pathologyTPKI kinaseTauopathiesTimeTissuesTrans active response DNA binding protein 43 pathologyTrans active response DNA binding protein of 43 kDa proteinopathyTranscriptTranscriptionTranslationsUntranslated RNAValidationactivating CRISPR technologyage associated dementiaage associated neurodegenerationage associated neurodegenerative diseaseage associated neurodegenerative disorderage associated pathologiesage dependent neurodegenerationage dependent neurodegenerative conditionage dependent neurodegenerative diseaseage dependent neurodegenerative disorderage dependent pathologiesage induced dementiaage induced pathologiesage related dementiaage related neurodegenerationage-driven neurodegenerative disordersage-related neurodegenerative diseaseage-related neurodegenerative disorderagesaging associated dementiaaging associated neurodegenerationaging associated neurodegenerative diseaseaging associated pathologiesaging dependent pathologiesaging induced pathologiesaging pathologiesaging related dementiaaging related neurodegenerationaging related neurodegenerative diseaseaging related neurodegenerative disorderaging related pathologiesallelic variantamyotrophic lateral sclerosis with frontotemporal dementiaamyotrophic lateral sclerosis/FTLDamyotrophic lateral sclerosis/frontotemporal dementiaamyotrophic lateral sclerosis/ftdataxin-3biological signal transductionbrain tissuecausationcell typeco-morbidco-morbiditycognitive dysfunctioncognitive losscomorbiditycomparativecrosslinkdegenerative diseases of motor and sensory neuronsdegenerative neurological diseasesdevelopmentaldifferential expressiondifferentially expresseddisease causationdisease riskdisorder riskeffective therapyeffective treatmentenvironmental riskexperimentexperimental researchexperimental studyexperimentsfront temporal dementiafrontal lobe dementiafrontotemporal dementia-amyotrophic lateral sclerosisfrontotemporal lobar degeneration dementiafrontotemporal lobar dementiafrontotemporal lobar dementia amyotrophic lateral sclerosisfrontotemporal lobe degeneration associated with dementiagenetic risk factorgenetic variantgenome scalegenome-widegenomewidegenomic variantglobal gene expressionglobal transcription profilehiPSC-derived neuronshuman iPSC-derived sensory neuronhuman induced pluripotent stem cell derived sensory neuroniPSiPS neuronsiPSCiPSC derived-neuronsiPSC-derived human neuroniPSCsinduced pluripotent cellinduced pluripotent stem cellinduced pluripotent stem cell neuronsinducible pluripotent cellinducible pluripotent stem cellinducible pluripotent stem cell derived human neuroninducible pluripotent stem cell derived human sensory neuroninherited factorinsightlimbic-predominant age-related TDP-43 encephalopathylimbic-predominant age-related TDP43 encephalopathyloss of functionmicrotubule bound taumicrotubule-bound taumortalitynecropsynerve cell deathnerve cell lossneural degenerationneurodegenerationneurodegenerativeneurodegenerative illnessneurological degenerationneuron cell deathneuron cell lossneuron deathneuron lossneuronalneuronal cell deathneuronal cell lossneuronal deathneuronal degenerationneuronal lossneurons derived from induced pluripotent stem cellsneurons differentiated from human induced pluripotent stem cellsneurons differentiated from induced pluripotent stem cellsneuropathologic tauneuropathological taunew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnoncodingnovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetoptogeneticspathophysiologypathwaypatient living with Alzheimer's diseasepatient populationpatient suffering from Alzheimer's diseasepatient with Alzheimer'spatient with Alzheimer's diseasepatients with ADpolyadenylatepost-transcriptional gene regulationpostmortempreventpreventingprimary degenerative dementiaprotein TDP-43protein TDP43repressing CRISPR-dCas9 systemsenile dementia of the Alzheimer typesocial roletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttautau Proteinstau associated neurodegenerationtau associated neurodegenerative processtau driven neurodegenerationtau factortau induced degenerationtau induced neurodegenerationtau kinasestau mediated neurodegenerationtau neurodegenerative diseasetau neuropathologytau pathologytau pathophysiologytau protein kinase Itau proteinopathytau related neurodegenerationtau-induced pathologytau-protein kinasetauopathic neurodegenerative disordertauopathytooltrans active response DNA binding protein 43 kDa pathologytrans active response DNA binding protein 43 proteinopathytranscriptional differencestranscriptometranscriptome sequencingtranscriptomic sequencingtranslationvalidationsτ Proteinsτ-protein kinase
Description preview
Project Summary: Age-related neurodegenerative diseases are a rapidly growing cause of mortality and
morbidity worldwide. The overwhelming majority of neurodegenerative disease, referred to as ‘sporadic,’ is
caused by poorly understood interactions between genetic and environmental risk factors. Due in part to the
complex etiology of…
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