grant
Genetic dysregulation of mRNA translation in type 1 diabetes
NIHUS FederalResearch GrantFY202612q135' Untranslated Regions5'UTRAffectAutoantigensAutoimmune DiabetesAutoimmune StatusAutoimmunityAutologous AntigensBeta CellBindingBiologic ModelsBiological ModelsBrittle Diabetes MellitusC-PeptideCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCaringCas nuclease technologyCausalityCellular biologyClustered 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 technologyComplications of Diabetes MellitusContinuous Glucose MonitorCoupledD-GlucoseDNA mutationDataData SetDependenceDevelopmentDevicesDextroseDiabetes ComplicationsDiabetes MellitusDiabetes-Related ComplicationsDiabetic ComplicationsDiseaseDisorderDrug TargetingDrug TherapyDrugsEtiologyFDA licensed drugsFDA-approved agentsFDA-approved drugFDA-approved medicationsFDA-approved pharmaceuticalsFDA-approved therapeutic agentFood and Drug Administration approved drugFood and Drug Administration approved medicationsFood and Drug Administration approved pharmaceuticalsGWA studyGWASGene ExpressionGenesGeneticGenetic ChangeGenetic DiversityGenetic MarkersGenetic PolymorphismGenetic RiskGenetic VariationGenetic defectGenetic mutationGenomic SegmentGlucoseGlycohemoglobin AGlycosylated hemoglobin AHb A1Hb A1a+bHb A1cHbA1HbA1cHemoglobin A(1)HeterogeneityHumanHumulin RHyperglycemiaIDDMImmune systemImpairmentIncidenceIndividualIndividual DifferencesInsulinInsulin CellInsulin Secreting CellInsulin-Dependent Diabetes MellitusIslet CellJuvenile-Onset Diabetes MellitusKetosis-Prone Diabetes MellitusMapsMediatingMedicationMendelian randomizationMessenger RNAMethodsMiceMice MammalsMinisatellite RepeatsMinisatellitesModel SystemModern ManMolecularMolecular InteractionMurineMusMutationNovolin ROnset of illnessOutcomePancreatic beta CellPancreatic β-CellPatientsPersonsPharmaceutical PreparationsPharmacological TreatmentPharmacotherapyPoint MutationPopulation HeterogeneityProteinsQOLQTLQuality of lifeQuantitative Trait LociRecombinant adeno-associated virusRecombinant adeno-associated virus (rAAV)Regular InsulinRegulationResidualResidual stateRibosomesRisk-associated variantSamplingSelf-AntigensSimple Repetitive SequenceStructure of beta Cell of isletSudden-Onset Diabetes MellitusT-CellsT-LymphocyteT1 DMT1 diabetesT1DT1DMTestingTranslatingTranslationsType 1 Diabetes MellitusType 1 diabetesType I Diabetes MellitusUpregulationVNTRVNTR LociVNTR RegionVNTR SequencesVariable Number of Tandem RepeatsVariable Tandem RepeatsVariantVariationautoreactive T cellbiobankbiorepositorycausationcell biologyco-morbidco-morbiditycomorbiditycompare to controlcomparison controlconnecting peptidecontinuous blood glucose monitorcontinuous blood sugar monitorcontinuous glucose measurementcontinuous sugar monitordevelopmentaldiabetesdiabetes controldiabetes geneticsdiabetes mellitus controldiabetes mellitus geneticsdiabetes riskdisease causationdisease onsetdisease riskdisorder onsetdisorder riskdiverse populationsdrug interventiondrug treatmentdrug/agenteffective therapyeffective treatmentendocrine cellgene biomarkergene expression biomarkergene markergene signature biomarkergenetic approachgenetic architecturegenetic biomarkergenetic strategygenome mutationgenome segmentgenome wide associationgenome wide association scangenome wide association studygenomewide association scangenomewide association studygenomic regionglycemic controlhemoglobin A1cheterogeneous populationhigh riskhigh risk grouphigh risk individualhigh risk peoplehigh risk populationhuman modelhyperglycemicimmunogenicityinsightinstrumentinsulin dependent diabetesinsulin dependent diabetes mellitus onsetinsulin dependent type 1isletjuvenile diabetesjuvenile diabetes mellitusketosis prone diabetesknock-downknockdownmRNAmRNA Leader SequencesmRNA Translationmodel of humanneo-antigenneo-epitopesneoantigensneoepitopesnerve cell deathnerve cell lossneuron cell deathneuron cell lossneuron deathneuron lossneuronal cell deathneuronal cell lossneuronal deathneuronal lossneurotoxicnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapypancreas beta cellpancreas β cellpancreatic b-cellpharmaceutical interventionpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticspolymorphismpopulation diversitypreservationpreventpreventingpromoterpromotorrAAVrecombinant AAVresponserisk allelerisk generisk genotyperisk locirisk locusrisk variantscRNA sequencingscRNA-seqself-reactive T cellshRNAshort hairpin RNAsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsmall hairpin RNAtargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmentthymus derived lymphocytetranslationtype 1 diabetes onsettype I diabetestype one diabetesvectorwhole genome association analysiswhole genome association studyβ-cellβ-cellsβCell
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Project Summary/Abstract
Type 1 diabetes (T1D), which is characterized by T cell-mediated destruction of insulin-producing pancreatic
beta cells, has a relatively well-defined genetic architecture that explains about 50% of inter-individual
differences in disease risk. However, translating the genetic architecture into novel disease insights and…
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