Unravelling Mechanisms and Novel Therapeutic Targets for Peripheral Neuropathy and Neuropathic Pain

周围神经病变和神经性疼痛的揭示机制和新治疗靶点

基本信息

  • 批准号:
    10534146
  • 负责人:
  • 金额:
    $ 132.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-12-15 至 2025-11-30
  • 项目状态:
    未结题

项目摘要

Damage to or loss of the peripheral axons of primary sensory neurons is associated with two clinical syndromes: peripheral neuropathic pain and peripheral neuropathy. Treatment for neuropathic pain is typically ineffective or associated with side effects, and there is no treatment for peripheral neuropathy. To remedy this, it is essential that the mechanisms responsible for both are understood and targets identified that could be amenable to development of novel therapeutics. My goal is to dissect out at an individual neuron level the transcriptional and functional changes that occur over time in response to physical axonal injury, ion channel mutations and exposure to neurotoxic cancer chemotherapeutic agents, and explore the extent to which hyperexcitability and axon degeneration are linked. This will involve combinations of several different approaches: correlating single cell profiles and disease related functional changes, identifying disease susceptibility in patient stem derived neurons, high content phenotypic screens, population imaging in intact animals, genetic editing, and interrogation at high temporal and spatial resolution of behavioral surrogates of pain and sensory loss. The project will focus on neuropathic pain due to physical disruption of peripheral sensory axons, small fiber neuropathies due to voltage-gated sodium channel mutations and chemotherapy- induced peripheral neuropathy, and will examine if these syndromes are distinct or part of a spectrum of sensory neuron pathologies with overlapping risk factors and mechanisms.
初级感觉神经元周围轴突的损伤或丢失与两种临床症状有关:周围神经病理性疼痛和周围神经病。神经性疼痛的治疗通常无效或与副作用相关,而且没有治疗周围神经病的方法。要纠正这一点,至关重要的是要了解两者的作用机制,并确定可以服从于新疗法开发的靶点。我的目标是在单个神经元水平上剖析随着时间的推移,由于物理轴突损伤、离子通道突变和暴露于神经毒性癌症化疗药物而发生的转录和功能变化,并探索过度兴奋和轴突退化之间的联系程度。这将涉及几种不同方法的组合:将单细胞图谱与疾病相关的功能变化相关联,确定患者干细胞来源神经元中的疾病易感性,高含量表型筛选,完整动物的种群成像,基因编辑,以及以高时空分辨率询问疼痛和感觉丧失的行为代用品。该项目将专注于周围感觉神经轴突物理破坏引起的神经病理性疼痛、电压门控钠通道突变引起的小纤维神经病以及化疗诱导的周围神经病,并将检查这些综合征是不同的,还是具有重叠风险因素和机制的感觉神经元病理谱的一部分。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

CLIFFORD J WOOLF其他文献

CLIFFORD J WOOLF的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('CLIFFORD J WOOLF', 18)}}的其他基金

Project 2: The cell types and states of painful neuromas
项目 2:疼痛性神经瘤的细胞类型和状态
  • 批准号:
    10594337
  • 财政年份:
    2022
  • 资助金额:
    $ 132.75万
  • 项目类别:
Project 2: The cell types and states of painful neuromas
项目 2:疼痛性神经瘤的细胞类型和状态
  • 批准号:
    10707429
  • 财政年份:
    2022
  • 资助金额:
    $ 132.75万
  • 项目类别:
Genetic Analysis and Manipulation Core (GAEC)
遗传分析和操作核心 (GAEC)
  • 批准号:
    10239466
  • 财政年份:
    2021
  • 资助金额:
    $ 132.75万
  • 项目类别:
Identification of susceptibility to chemotherapy induced peripheral neuropathy using patient stem cell derived sensory neurons
使用患者干细胞来源的感觉神经元鉴定对化疗引起的周围神经病变的易感性
  • 批准号:
    9385404
  • 财政年份:
    2017
  • 资助金额:
    $ 132.75万
  • 项目类别:
Unravelling mechanisms and novel therapeutic targets for peripheral neuropathy and neuropathic pain
周围神经病和神经性疼痛的揭示机制和新治疗靶点
  • 批准号:
    10063580
  • 财政年份:
    2017
  • 资助金额:
    $ 132.75万
  • 项目类别:
Unravelling Mechanisms and Novel Therapeutic Targets for Peripheral Neuropathy and Neuropathic Pain (Diversity Supplement)
周围神经病变和神经性疼痛的揭示机制和新治疗靶点(多样性补充)
  • 批准号:
    10742137
  • 财政年份:
    2017
  • 资助金额:
    $ 132.75万
  • 项目类别:
Unravelling mechanisms and novel therapeutic targets for peripheral neuropathy and neuropathic pain
周围神经病和神经性疼痛的揭示机制和新治疗靶点
  • 批准号:
    10320363
  • 财政年份:
    2017
  • 资助金额:
    $ 132.75万
  • 项目类别:
Microglia, Complement, and Pain
小胶质细胞、补体和疼痛
  • 批准号:
    7903813
  • 财政年份:
    2009
  • 资助金额:
    $ 132.75万
  • 项目类别:
Tetrahydrobiopterin and pain
四氢生物蝶呤与疼痛
  • 批准号:
    7752780
  • 财政年份:
    2008
  • 资助金额:
    $ 132.75万
  • 项目类别:
Tetrahydrobiopterin and pain
四氢生物蝶呤与疼痛
  • 批准号:
    7912421
  • 财政年份:
    2008
  • 资助金额:
    $ 132.75万
  • 项目类别:

相似海外基金

The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
  • 批准号:
    EP/Z000920/1
  • 财政年份:
    2025
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
  • 批准号:
    FT230100276
  • 财政年份:
    2024
  • 资助金额:
    $ 132.75万
  • 项目类别:
    ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
  • 批准号:
    MR/X024261/1
  • 财政年份:
    2024
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
  • 批准号:
    DE240100388
  • 财政年份:
    2024
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Discovery Early Career Researcher Award
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
  • 批准号:
    2232190
  • 财政年份:
    2023
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Continuing Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
  • 批准号:
    2337595
  • 财政年份:
    2023
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
  • 批准号:
    23K17514
  • 财政年份:
    2023
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Analysis of thermoregulatory mechanisms by the CNS using model animals of female-dominant infectious hypothermia
使用雌性传染性低体温模型动物分析中枢神经系统的体温调节机制
  • 批准号:
    23KK0126
  • 财政年份:
    2023
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Fund for the Promotion of Joint International Research (International Collaborative Research)
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
  • 批准号:
    2842926
  • 财政年份:
    2023
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
  • 批准号:
    NC/X001644/1
  • 财政年份:
    2023
  • 资助金额:
    $ 132.75万
  • 项目类别:
    Training Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了