grant
A Novel RAD51-BRCA2 Complex Stabilizing Drug: A Medical Countermeasure for Mitigating Accidental Radiation Exposure
Organization UNIVERSITY OF ARIZONALocation TUCSON, UNITED STATESPosted 16 Sept 2025Deadline 31 Aug 2030
NIHUS FederalResearch GrantFY2025AccelerationAccidentsAcuteAcute Radiation SyndromeAddressAdverse Late EffectsAffinityAgeAlimentary CanalAnimal ModelAnimal Models and Related StudiesAssayBRCA2BRCA2 Gene ProductBRCA2 ProteinBRCA2 geneBindingBioassayBiodistributionBiological AssayBiophysicsBlood PlasmaBlood VesselsBody TissuesBone MarrowBone Marrow Reticuloendothelial SystemBreast Cancer 2 GeneBreast Cancer 2 Gene ProductBreast Cancer Type 2 Susceptibility GeneBreast Cancer Type 2 Susceptibility ProteinC57BL/6 MouseCardiac Muscle CellsCardiac MyocytesCardiac ToxicityCardiocyteCardiotoxicCardiotoxicityCell BodyCell Communication and SignalingCell Culture TechniquesCell CycleCell DeathCell Division CycleCell SignalingCell SurvivalCell ViabilityCellsCessation of lifeChaperoneChromosomal InstabilityChromosome InstabilityChromosomesComplexDNADNA DamageDNA Damage RepairDNA Double Strand BreakDNA InjuryDNA RepairDNA ReplicationDNA SynthesisDNA biosynthesisDNA fiber analysisDNA fiber approachDNA fiber assayDNA fiber combingDNA fiber methodDNA fiber spreadingDNA fiber techniqueDNA replication forkDataDeathDeoxyribonucleic AcidDevelopmentDigestive TractDisease-Free SurvivalDoseDouble Strand Break RepairDrug KineticsDrugsEarly Onset Gene Breast Cancer 2Early Onset Protein Breast Cancer 2EffectivenessEvent-Free SurvivalExposure toFANCD1FormulationFrequenciesG2 PhaseG2 periodGI Stem cellGI TractGap Phase 2Gastrointestinal TractGastrointestinal tract structureGoalsHealthHeart Muscle CellsHeart myocyteHereditary Breast Cancer 2HourHumanIn VitroIntestinalIntestinesIntracellular Communication and SignalingInvadedIonizing Electromagnetic RadiationIonizing radiationKineticsLate EffectsLigandsLinkLytotoxicityMediatingMedicationMetaphaseMiceMice MammalsMitoticMitotic MetaphaseModelingModern ManMolecular ChaperonesMolecular InteractionMorbidityMorbidity - disease rateMouse StrainsMurineMusNormal TissueNormal tissue morphologyPathway interactionsPharmaceutical PreparationsPharmacodynamicsPharmacokineticsPlasmaPlasma SerumProliferatingProteinsQOLQuality of lifeRAD51 proteinRad51 recombinaseRadiationRadiation AccidentsRadiation InjuriesRadiation SensitivityRadiation ToleranceRadiation ToxicityRadiation exposureRadiation induced double strand breakRadiation-Ionizing TotalRadiosensitivityRadiotoxicityRegimenReticuloendothelial System, Serum, PlasmaRiskRouteSafetySecond Gap PhaseSeriesSignal TransductionSignal Transduction SystemsSignalingSingle-Stranded DNASiteSpecificityStructureTestingTherapeuticTissuesTotal Body IrradiationToxic effectToxicitiesUnscheduled DNA SynthesisWhole-Body IrradiationWhole-Body Radiationagesalimentary tractanalogbiological signal transductionbiophysical approachesbiophysical foundationbiophysical methodologybiophysical methodsbiophysical principlesbiophysical sciencesbiophysical techniquesbowelbrca 2 genecardiac functioncardiomyocytecell culturecell culturescytotoxicitydesigndesigningdetermine efficacydevelopmentaldigestive canaldosagedrug/agentefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationevaluate efficacyexamine efficacyfunction of the heartgastrointestinalgastrointestinal stem cellgenome integritygenomic integritygut progenitorgut stem cellheart functionhomologous recombinationimprovedinsightintestinal progenitorintestinal stem cellsintraperitonealionizing outputirradiation injurymedical countermeasuremodel of animalmortalitynecrocytosisnew approachesnovelnovel approachesnovel strategiesnovel strategypathwaypre-clinicalpreclinicalpreventpreventingradiation disasterradiation eventradiation incidentradiation induced DSBradiation induced tissue injuryradiation mitigationradiation poisoningradiation-induced tissue damageradio-sensitivityradiological accidentradiological disasterradiological eventradiological incidentradiological mitigationradiomitigationradiosensitiverecombinaserecruitrepairrepairedreplication forksmall moleculessDNAvascular
Description preview
Abstract
Ionizing radiation (IR) exposure from accidents or warfare can cause severe damage to radiosensitive tissues,
such as bone marrow, intestines, and blood vessels, leading to acute radiation syndrome (ARS) and delayed
effects of acute radiation exposure (DEARE) with high mortality and morbidity. These effects are mainly due to
DNA…
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