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Functional Analysis of Pathogenic Human PTEN Variants in Early Neurodevelopment
Organization YALE UNIVERSITYLocation NEW HAVEN, UNITED STATESPosted 16 Dec 2022Deadline 30 Apr 2025 β οΈ
NIHUS FederalResearch GrantFY20250-11 years oldAKTASDAddressAffectAkt proteinAllelesAllelomorphsAutismAutistic DisorderAutomobile DrivingBehaviorBehavior Conditioning TherapyBehavior ModificationBehavior TherapyBehavior TreatmentBehavioralBehavioral Conditioning TherapyBehavioral ModificationBehavioral TherapyBehavioral TreatmentBiologicalBrachydanio rerioBrainBrain Nervous SystemBrain VentricleCRISPR 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 technologyCas nuclease technologyCell BodyCell CycleCell DifferentiationCell Differentiation processCell Division CycleCell Growth in NumberCell MultiplicationCell ProliferationCellsCellular ExpansionCellular GrowthCellular ProliferationCerebral VentriclesChildChild YouthChildhoodChildren (0-21)ClinicalClustered 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 technologyComputer softwareConditioning TherapyCongenital HydrocephalusDNA mutationDanio rerioDataDiseaseDisorderDrug TargetingDrug TherapyEarly Infantile AutismEmbryoEmbryonicEncephalonExhibitsExonsFK506 Binding Protein 12-Rapamycin Associated Protein 1FKBP12 Rapamycin Complex Associated Protein 1FRAP1FRAP1 geneFRAP2FecundabilityFecundityFertilityFishesFrame Shift MutationFrameshift MutationGene Copy NumberGene DosageGene variantGenesGeneticGenetic ChangeGenetic defectGenetic mutationGenomeGoalsHead circumferenceHeterozygoteHumanHuman PathologyImmunoblottingImmunohistochemistryImmunohistochemistry Cell/TissueImmunohistochemistry Staining MethodInfantile AutismInjectionsInvestigationKanner's SyndromeLarvaLibrariesLiquid substanceMMAC1MMAC1 proteinMacrocephalyMechanistic Target of RapamycinMegacephalyMegalocephalyMessenger RNAMetabolic PathwayMethodsModelingModern ManMolecularMutated in Multiple Advanced Cancers 1MutationNerve CellsNerve UnitNeural CellNeural DevelopmentNeurocyteNeurodevelopmental DisorderNeurological Development DisorderNeuronsOperative ProceduresOperative Surgical ProceduresOutcomeOutcomes ResearchPHTS genePHTS proteinPTENPTEN genePTEN proteinPTEN1PathogenesisPathogenicityPathologyPathway interactionsPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPharmacological TreatmentPharmacotherapyPhenotypePhosphatase and Tensin HomologPhosphatase and Tensin Homolog Deleted on Chromosome 10PlayPre-Clinical ModelPreclinical ModelsPrevalenceProcessProliferatingProtein BiosynthesisProtein Kinase BProto-Oncogene Proteins c-aktRAC-PK proteinRAFT1RapamuneRapamycinReading Frame Shift MutationReportingResearchRestRibosomal Peptide BiosynthesisRibosomal Protein BiosynthesisRibosomal Protein SynthesisRisk-associated variantRoleScreening procedureSirolimusSoftwareStartle ReactionSurgicalSurgical InterventionsSurgical ProcedureSymptomsSystemTestingUnited StatesVariantVariationWestern BlottingWestern ImmunoblottingZebra DanioZebra FishZebrafishallelic variantautism spectral disorderautism spectrum disorderautistic childrenautistic spectrum disorderbehavior interventionbehavior phenotypebehavioral interventionbehavioral phenotypingbiologicbrain volumec-akt proteincell growthcellular differentiationchildren on the autism spectrumchildren with ASDchildren with autismchildren with autism spectrum disorderdisease riskdisorder riskdrivingdrug interventiondrug treatmentearly childhoodexome sequencingexome-seqfetalfluidgenetic variantgenome mutationgenomic variantheterozygosityhigh-throughput drug screeningimprovedin vivoinhibitorinsightkidsliquidloss of functionmRNAmTORmTOR Signaling Pathwaymammalian target of rapamycinmembermutantmutated in multiple advanced cancers 1 proteinneuralneural circuitneural circuitryneurocircuitryneurodevelopmentneurodevelopmental diseaseneurogenesisneuronalnew approachesnew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovelnovel approachesnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel strategiesnovel strategynovel therapeutic targetnovel therapy targetpathwaypatient oriented outcomespediatricpharmaceutical interventionpharmacologicpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticsphosphatase and tensin homologue on chromosome tenpleiotropic effectpleiotropismpleiotropyprotein blottingprotein protein interactionprotein synthesisproto-oncogene protein RACproto-oncogene protein aktrac protein kinaserelated to A and C-proteinrisk allelerisk generisk genotyperisk locirisk locusrisk variantscreeningscreening toolsscreeningssocial rolestartle responsesurgerysynaptic circuitsynaptic circuitrytargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmentteleostyoungster
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Project Summary/Abstract
PTEN is highly associated with autism, macrocephaly, and congenital hydrocephalus, which are increasingly
prevalent neurodevelopmental disorders that present in early childhood. Currently, there are no treatments that
address the cause of these conditions, despite mounting genetic evidence through large scale whole exomeβ¦
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