Defining the MAST4 interactome in brain development and epilepsy
定义大脑发育和癫痫中的 MAST4 相互作用组
基本信息
- 批准号:10664122
- 负责人:
- 金额:$ 21.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAlzheimer&aposs DiseaseAxonBindingBiochemicalBrainBrain regionCandidate Disease GeneCellsCellular MorphologyChildChildhoodCo-ImmunoprecipitationsDataDevelopmentDevelopmental Delay DisordersEligibility DeterminationEpilepsyFamilyFutureGenesGeneticGenetic Predisposition to DiseaseGrowthHealthHealthcareHumanImmunohistochemistryImpairmentIn VitroIndividualLabelMass Spectrum AnalysisMicrotubulesMolecular DiagnosisMorbidity - disease rateMorphologyMouse ProteinMusMutationN-terminalNervous System PhysiologyNeurologic DysfunctionsNeuronsPathogenicityPatientsPharmaceutical PreparationsPhosphotransferasesPropertyProtein-Serine-Threonine KinasesProteinsProteomicsRattusReagentResourcesSeizuresSocietiesSynapsesTestingTranscriptValidationVariantVisionWestern Blottingautism spectrum disorderbrain abnormalitiescausal variantchildhood epilepsycortical visual impairmentcostde novo mutationdrug developmentepileptic encephalopathiesexperimental studygenetic disorder diagnosishuman fetal brainin vivomembermortalitymutantnervous system disorderneurodevelopmentneuroimagingprecision medicinepreventprotein expressionquantitative imagingrapid diagnosisscreeningspatiotemporaltherapeutic targettool
项目摘要
PROJECT SUMMARY
Epilepsy is a common and costly cause of morbidity and mortality in children and adults. Developmental and
epileptic encephalopathies (DEEs) are severe childhood epilepsies that require rapid diagnosis to initiate
treatment that will control seizures and prevent or reverse the loss of neurologic function. However, these
seizures often do not respond to medications. Most DEE patients are expected to have a known underlying
genetic etiology, but they often lack a molecular diagnosis because the potential pathogenic variants are in
genes that have not yet been associated with neurological dysfunction. We have identified de novo variants in
the MAST4 gene in patients with developmental delay, DEE, vision abnormalities, and in some, structural brain
abnormalities. MAST4 is a member of an understudied family of serine threonine kinases (MAST1-4 and
MAST-like) that is among the IDG-eligible proteins with high potential to impact human health as a therapeutic
target for epilepsy. In Aim 1, we will characterize MAST4 spatiotemporal expression in neurodevelopment and
identify MAST4 interacting proteins in vivo using label-free mass spectrometry. In Aim 2, we will validate
MAST4 interacting proteins and the impact of patient-specific mutations on these interactions in primary
cultured neurons in vitro. The results from these experiments will provide both important functional data and
tools to instruct the path to precision medicine for DEE patients with MAST4 mutations.
项目总结
项目成果
期刊论文数量(0)
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Kimberly Anne Aldinger其他文献
Kimberly Anne Aldinger的其他文献
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{{ truncateString('Kimberly Anne Aldinger', 18)}}的其他基金
Investigating the cellular and molecular neuropathology of the cerebellum in autism
研究自闭症小脑的细胞和分子神经病理学
- 批准号:
10417052 - 财政年份:2021
- 资助金额:
$ 21.22万 - 项目类别:
Investigating the cellular and molecular neuropathology of the cerebellum in autism
研究自闭症小脑的细胞和分子神经病理学
- 批准号:
10195945 - 财政年份:2021
- 资助金额:
$ 21.22万 - 项目类别:
Determining the neurodevelopmental cell type specific regulatory networks impacted in Down syndrome
确定唐氏综合症影响的神经发育细胞类型特异性调节网络
- 批准号:
10595260 - 财政年份:2021
- 资助金额:
$ 21.22万 - 项目类别:
Determining the neurodevelopmental cell type specific regulatory networks impacted in Down syndrome
确定唐氏综合症影响的神经发育细胞类型特异性调节网络
- 批准号:
10304101 - 财政年份:2021
- 资助金额:
$ 21.22万 - 项目类别: