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

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.
项目摘要 癫痫是儿童和成人发病和死亡的常见且昂贵的原因。发展和 癫痫性脑病(DEE)是严重的儿童癫痫,需要快速诊断, 控制癫痫发作和预防或逆转神经功能丧失的治疗。但这些 癫痫发作通常对药物没有反应。预计大多数DEE患者具有已知的基础疾病, 遗传病因学,但他们往往缺乏分子诊断,因为潜在的致病变异是在 尚未发现与神经功能障碍有关的基因。我们已经确定了新的变异, MAST 4基因在发育迟缓、DEE、视力异常和某些结构性脑疾病患者中的作用 异常MAST 4是未充分研究的丝氨酸苏氨酸激酶家族(MAST 1 -4和MAST 2)的成员。 MAST样),其是IDG合格蛋白质之一,具有作为治疗剂影响人类健康的高潜力 目标是癫痫在目标1中,我们将描述MAST 4在神经发育中的时空表达, 使用无标记质谱法在体内鉴定MAST 4相互作用蛋白。在目标2中,我们将验证 MAST 4相互作用蛋白和患者特异性突变对原发性肝癌中这些相互作用的影响 体外培养神经元。这些实验的结果将提供重要的功能数据, 工具来指导MAST 4突变的DEE患者的精准医疗路径。

项目成果

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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:
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