grant
Calcium Release Channel Deficiency Syndrome
Organization MAYO CLINIC ROCHESTERLocation ROCHESTER, UNITED STATESPosted 1 Jun 2024Deadline 31 Mar 2028
NIHUS FederalResearch GrantFY20255' Untranslated Regions5'UTRAddressAdrenalineAmishArrhythmiaAsystoleAutopsyBiologyBiophysicsCa Release Channel-Ryanodine ReceptorCaffeineCalciumCalcium-Ryanodine Receptor ComplexCardiacCardiac ArrestCardiac ArrhythmiaCardiac DiseasesCardiac DisordersCardiac Muscle CellsCardiac MyocytesCardiac developmentCardiocyteCardiologyCatecholaminergic Polymorphic Ventricular TachycardiaCell Communication and SignalingCell FunctionCell LineCell PhysiologyCell ProcessCell SignalingCell modelCellLineCellular FunctionCellular PhysiologyCellular ProcessCellular modelCessation of lifeClinical ManagementCodeCoding SystemCommunitiesCouplingDeathDevelopmentDiseaseDisorderECGEKGEchocardiogramEchocardiographyElectrocardiogramElectrocardiographyElectrophysiologyElectrophysiology (science)EngineeringEpinephrineEventExerciseExertionExonsExperimental DesignsFaintingFamily memberFrequenciesFunctional RNAGenerationsGeneticGenotypeHealthHeartHeart ArrestHeart ArrhythmiasHeart DiseasesHeart Muscle CellsHeart myocyteHereditaryHeritabilityHeterozygoteHolter ElectrocardiographyHolter MonitoringHoltmonHourHyperactivityIndividualInheritedIntegraseIntercistronic SequenceIntergenic SequenceInternationalIntracellular Communication and SignalingIsoprenalineIsopropyl NoradrenalineIsopropylarterenolIsopropylnoradrenalineIsopropylnorepinephrineIsoproterenolIsuprelKineticsKnowledgeLeadLinkMeasurableMediatingMissense MutationModelingMolecularNatureNeurophysiology / ElectrophysiologyNoncoding RNANontranslated RNAPathogenicityPatientsPb elementPhenotypePromoter RegionsPromotor RegionsPropertyProteinsRegistriesResolutionRyanodine ReceptorRyanodine Receptor Calcium Release ChannelSERCA2aSecondary toSignal TransductionSignal Transduction SystemsSignalingStrains Cell LinesStress TestsSubcellular ProcessSyncopeSyndromeSystemTestingTherapeutic EpinephrineTranscriptTransthoracic EchocardiographyUntranslated RNAVariantVariationVentricular Arrhythmiaautosomebiological signal transductionbiophysical foundationbiophysical principlesbiophysical sciencescardiac myocytes differentiated from induced pluripotent stem cellcardiogenesiscardiomyocytecell regenerationcellular regenerationclinical diagnosisclinical phenotypecompare to controlcomparison controlcultured cell linedevelopmentaldosageelectrophysiologicalgain of functiongenetic promoter elementgenetic promoter sequencegenome sequencingheart cellheart developmentheart disorderheart formationheart sonographyheavy metal Pbheavy metal leadheterozygosityiPSiPS cell derived cardiomyocytesiPSCiPSC derived cardiomyocytesiPSCsinduced pluripotent cellinduced pluripotent stem cellinduced pluripotent stem cell derived cardiac myocytesinduced pluripotent stem cell derived cardiomyocytesinducible pluripotent cellinducible pluripotent stem cellinducible pluripotent stem cell derived cardiac myocytesinducible pluripotent stem cells derived cardiomyocytesinnovateinnovationinnovativeloss of functionmRNA Leader Sequencesmissense single nucleotide polymorphismmissense single nucleotide variantmissense variantnecropsynew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnoncodingnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapypostmortempromoter sequenceprotein expressionprotein functionresolutionsresponserisk stratificationshRNAshort hairpin RNAsmall hairpin RNAstemstratify riskstructural mutationstructural variantstructural variationsudden cardiac deathunclassified variantvariant of uncertain clinical significancevariant of uncertain significancevariant of undetermined significancevariant of unknown significance
Description preview
PROJECT SUMMARY
Potentially lethal cardiac channelopathies associated with pathogenic variants in the RYR2-encoded
cardiac ryanodine receptor type 2 (RyR2)/calcium release channel (CRC) are the pathogenic basis for
a significant portion of autopsy-negative sudden unexplained death in the young (SUDY). RYR2 gain-
of-function (GOF) pathogenic…
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