High-Resolution Spatial MIST Technology for Functional Proteomic Study of Neuroinflammation in Alzheimer's Disease

高分辨率空间 MIST 技术用于阿尔茨海默病神经炎症的功能蛋白质组学研究

基本信息

  • 批准号:
    10343115
  • 负责人:
  • 金额:
    $ 46.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-01-15 至 2024-12-31
  • 项目状态:
    已结题

项目摘要

Summary Alzheimer’s disease (AD) is the most common form of dementia and is a looming crisis in the US. Despite substantial progress made in AD research, the molecular and cellular processes governing neurodegeneration are still not well understood, and AD therapies have not resulted in significant benefits to patients. The traditional hallmarks of AD include amyloid beta aggregation and neurofibrillary tangle deposition, while recently inflammation, an innate immune response in the brain, emerges as a third hallmark. Inflammation particularly occurs near epicenters of amyloid beta plagues and neurofibrillary tangles, and it involves complicated cellular interactions that synergize with the progression of neurodegeneration. Understanding the molecular mechanisms of the functional roles of the cells in neuroinflammation and its influences on neurons is the key to searching for effective therapeutic targets. Due to the nature of high complexity and spatial heterogeneity, recent research has vastly turned to next generation sequencing and transcriptomics tools in neurodegeneration studies. These results on gene expression will still need protein-level validation since proteins carry out most of cellular functions and biochemical processes. The current multiplexed protein assays on tissue samples are either labor intensive and low coverage or in low spatial resolution. In this project, we aim to develop a spatial proteomics technology with cellular resolution to fill the technological gap and timely address the most imperative issues in AD mechanisms. This technology is built upon a multiplex in situ tagging (MIST) array that measures ~200 AD relevant proteins from single neurons in our preliminary study. With ~10-100X higher multiplexity than other spatial protein tools, our spatial MIST will measure most important regulatory proteins and markers in spatially localized cells of brain sections. Two specific aims we propose include (1) Optimize the experimental techniques in spatial MIST for detecting 280 key proteins in signaling and regulation of whole mouse brain slices, and (2) Profile the molecular features of cells near Aβ accumulation and tau enriched regions by spatial MIST during AD progression. The completion of this project will generate an enabling technology and method widely accessible in the AD research community to investigate AD pathogenesis from a new, clinically relevant perspective. This technology will lay the foundation for future mechanistic studies of AD development and identification of potential therapeutic targets.
总结

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Rapid, High-Throughput Single-Cell Multiplex In Situ Tagging (MIST) Analysis of Immunological Disease with Machine Learning.
  • DOI:
    10.1021/acs.analchem.3c01157
  • 发表时间:
    2023-05-16
  • 期刊:
  • 影响因子:
    7.4
  • 作者:
    Yang, Liwei;Dutta, Pratik;Davuluri, Ramana V.;Wang, Jun
  • 通讯作者:
    Wang, Jun
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Jun Wang其他文献

Spiking Neural Systems with Weights
带权重的尖峰神经系统
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Jun Wang;Hendrik Jan Hoogeboom;Gheorghe Paun;Linqiang Pan
  • 通讯作者:
    Linqiang Pan

Jun Wang的其他文献

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{{ truncateString('Jun Wang', 18)}}的其他基金

Striatal ensemble plasticity in alcohol use disorder
酒精使用障碍中的纹状体整体可塑性
  • 批准号:
    10734890
  • 财政年份:
    2023
  • 资助金额:
    $ 46.25万
  • 项目类别:
Development of dual inhibitors targeting the viral main protease and the host cathepsin L as SARS-CoV-2 antivirals
开发针对病毒主要蛋白酶和宿主组织蛋白酶 L 的双重抑制剂作为 SARS-CoV-2 抗病毒药物
  • 批准号:
    10457835
  • 财政年份:
    2022
  • 资助金额:
    $ 46.25万
  • 项目类别:
Repurposing of Maraviroc for the treatment of neuropathic pain
重新利用马拉韦罗治疗神经性疼痛
  • 批准号:
    10586296
  • 财政年份:
    2022
  • 资助金额:
    $ 46.25万
  • 项目类别:
Sex-specific role of CCL5/CCR5 axis in depression and its therapeutic implication
CCL5/CCR5轴在抑郁症中的性别特异性作用及其治疗意义
  • 批准号:
    10364861
  • 财政年份:
    2022
  • 资助金额:
    $ 46.25万
  • 项目类别:
NanoDiagnotic Technology I-Corps Training
纳米诊断技术 I-Corps 培训
  • 批准号:
    10541690
  • 财政年份:
    2022
  • 资助金额:
    $ 46.25万
  • 项目类别:
Development of dual inhibitors targeting the viral main protease and the host cathepsin L as SARS-CoV-2 antivirals
开发针对病毒主要蛋白酶和宿主组织蛋白酶 L 的双重抑制剂作为 SARS-CoV-2 抗病毒药物
  • 批准号:
    10543633
  • 财政年份:
    2022
  • 资助金额:
    $ 46.25万
  • 项目类别:
Development of dual inhibitors targeting the viral main protease and the host cathepsin L as SARS-CoV-2 antivirals
开发针对病毒主要蛋白酶和宿主组织蛋白酶 L 的双重抑制剂作为 SARS-CoV-2 抗病毒药物
  • 批准号:
    10693823
  • 财政年份:
    2022
  • 资助金额:
    $ 46.25万
  • 项目类别:
Sex-specific role of CCL5/CCR5 axis in depression and its therapeutic implication
CCL5/CCR5轴在抑郁症中的性别特异性作用及其治疗意义
  • 批准号:
    10653682
  • 财政年份:
    2022
  • 资助金额:
    $ 46.25万
  • 项目类别:
Rapid detection of infectious viral particles by cluster induced exhaustive reaction
通过簇诱导穷举反应快速检测感染性病毒颗粒
  • 批准号:
    10443877
  • 财政年份:
    2021
  • 资助金额:
    $ 46.25万
  • 项目类别:
Development of dual inhibitors targeting the viral main protease and the host cathepsin L as SARS-CoV-2 antivirals
开发针对病毒主要蛋白酶和宿主组织蛋白酶 L 的双重抑制剂作为 SARS-CoV-2 抗病毒药物
  • 批准号:
    10191875
  • 财政年份:
    2021
  • 资助金额:
    $ 46.25万
  • 项目类别:

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