grant
Novel endogenous and engineered activators of STING: from mechanisms to cancer therapy
Organization UT SOUTHWESTERN MEDICAL CENTERLocation DALLAS, UNITED STATESPosted 3 Apr 2025Deadline 31 Mar 2030
NIHUS FederalResearch GrantFY2025AgonistAnimal ModelAnimal Models and Related StudiesAnimalsAntitumor ResponseBindingBiochemistry and Cellular BiologyBody TissuesCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCancer PatientCancer TreatmentCancersCell BodyCell Communication and SignalingCell DeathCell SignalingCellsChemosensitizationChemosensitization/PotentiationCholesterolCirculatory CollapseColorectal NeoplasmsColorectal TumorsComplexCryo-electron MicroscopyCryoelectron MicroscopyCytotoxic cellDataDendritic CellsDevelopmentDrug KineticsDrug TargetingDrugsElectron CryomicroscopyElectronsEncapsulatedEndoplasmic ReticulumEngineeringErgastoplasmExhibitsFoundationsGene ActivationGolgiGolgi ApparatusGolgi ComplexHost DefenseHost Defense MechanismImmuneImmune Cell ActivationImmune responseImmune signalingImmune systemImmunesIn VitroIndividualInnate ImmunityInterferon Type IIntracellular Communication and SignalingK lymphocyteKnowledgeLarge Bowel TumorLarge Intestine NeoplasmLarge Intestine TumorLigandsLipidsLysosomesMC-38MC38Malignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMediatingMedicationMembraneModelingMolecularMolecular InteractionMonitorMyelogenousMyeloidMyeloid CellsNK CellsNative ImmunityNatural ImmunityNatural Killer CellsNegative Beta ParticleNegatronsNon-Specific ImmunityNonspecific ImmunityNormal TissueNormal tissue morphologyPIP2Pharmaceutical PreparationsPharmacokineticsPhosphatidyl Inositol PhosphatesPhosphatidylinositol 4,5-BiphosphatePhosphatidylinositol 4,5-DiphosphatePhosphatidylinositol PhosphatesPhosphatidylinositol-4,5-BisphosphatePhysical condensationPlayPolymersPolyphosphoinositidesPopulationPotentiationProteinsPtIns 4,5-P2PtdInsP2RegulationResearchResolutionRoleShockSignal TransductionSignal Transduction SystemsSignalingSignaling Factor Proto-OncogeneSignaling Pathway GeneSignaling ProteinSiteStimulator of Interferon GenesStructureSurfaceT-CellsT-LymphocyteT8 CellsT8 LymphocytesTM DomainTestingTissuesToxic effectToxicitiesTransmembrane DomainTransmembrane RegionTreatment EfficacyTumor ImmunityVeiled Cellsadaptive immunityanti-cancer immunotherapyanti-cancer therapyanti-tumor effectanti-tumor immunityanti-tumor responseanticancer immunotherapyantitumor effectantitumor immunitybiological signal transductioncGAMP STINGcGAMP-STINGcGAMP/STINGcGAS/STINGcancer immunitycancer immunotherapycancer therapycancer-directed therapycirculatory shockcolorectal neoplasiacondensationcryo-EMcryoEMcryogenic electron microscopycyclic GMP-AMP synthase/STINGdefense responsedesigndesigningdevelopmentaldrug/agentearly clinical trialearly phase clinical trialfunctional groupgene functionhazardhost responseimmune activationimmune system responseimmune-based cancer therapiesimmunogenicimmunoresponseimmunotherapy for cancerimmunotherapy of cancerimprovedin vivoinsightintervention efficacylarge bowel neoplasmmalignancymembrane structuremodel of animalmouse modelmurine modelnano particlenano-sized particlenanoparticlenanosized particlenecrocytosisneoplasm/cancernew approachesnext generationnovelnovel approachesnovel strategiesnovel strategyparticlephysiological defense responsepolymerpolymericpre-clinicalpre-clinical studypreclinicalpreclinical studyrational designresolutionsresponseshocksside effectsmall moleculesocial rolespatial and temporalspatial temporalspatiotemporalstructural biologysuccesssynergismtargeted cancer therapytherapeutic efficacytherapy efficacythymus derived lymphocytetumor
Description preview
STING is an ER-associated membrane innate immune protein vital for cancer defense. Despite
promising preclinical results, STING agonists have not shown significant success in early clinical
trials due to complex signaling, transient activation as a result lysosomal degradation, and
detrimental side-effects on healthy tissues. The first Aim of this…
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