Regulation of apoptotic priming and competence in healthy and cancerous cells

健康细胞和癌细胞中凋亡启动和能力的调节

基本信息

  • 批准号:
    8767377
  • 负责人:
  • 金额:
    $ 9.05万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-09-01 至 2016-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Treatment of human cancers with chemotherapy or radiation with curative intent has led to the successful eradication of malignancies in millions of patients, yet the apoptotic cell death induced in healthy tissues drastically limits the use of thee crucial therapies. This is especially true in pediatric patients that, for example, commonly experience cardiotoxicity from doxorubicin treatment or neuronal apoptosis after brain irradiation. Adults exhibit dramatically less toxicity than children from these same treatments but the basis for this difference in sensitivity is unknown. Using BH3 profiling, an innovative tool to measure how close cells are to the threshold of apoptosis, we recently observed novel and striking differences in the how apoptosis is regulated in vital tissues that challenge the existing dogma in the field. These observations also create opportunities to improve existing therapies and develop novel classes of anti-cancer drugs. Within this proposal, we plan to first develop a comprehensive understanding of how differential regulation of apoptosis affects cell fate in response to damage or stress in vivo (Aim 1). Using gene expression analysis and mouse models, we will then identify the molecular mechanisms that control these pathways (Aim 2). Finally, we will utilize our newfound knowledge to identify and develop agents that will reduce toxicity from current treatments or represent novel classes of anti-cancer therapies (Aim 3). By understanding and modulating apoptosis programs in healthy and cancerous cells we will improve patient outcomes.
描述(申请人提供):用化疗或放射疗法治疗人类癌症,有治疗意图,已导致数百万人成功根除恶性肿瘤 然而,健康组织中诱导的凋亡细胞死亡极大地限制了这三种关键疗法的使用。这在儿科患者中尤其如此,例如,他们通常会经历阿霉素治疗的心脏毒性或脑照射后神经元的凋亡。成年人的毒性比儿童要小得多,但 这种敏感度差异的基础尚不清楚。使用BH3评测,这是一种创新的工具 测量细胞离凋亡阈值有多近,我们最近观察到在重要组织中如何调控细胞凋亡的新的和显著的差异,这些差异挑战了现有的 赛场上的教条。这些观察结果也为改进现有疗法和开发新型抗癌药物创造了机会。在这项提案中,我们计划首先全面了解细胞凋亡的不同调控如何影响细胞命运,以应对体内的损伤或应激(目标1)。利用基因表达分析和小鼠模型,我们将确定控制这些途径的分子机制(目标2)。最后,我们将利用我们新发现的知识来确定和开发将减少当前治疗方法的毒性或代表新的抗癌疗法类别的药物(目标3)。通过了解和调节健康和癌细胞的凋亡程序,我们将改善患者的预后。

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 }}

Kristopher Andrew Sarosiek其他文献

Kristopher Andrew Sarosiek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('Kristopher Andrew Sarosiek', 18)}}的其他基金

Developmental regulation of apoptosis as a modifiable driver of radiotherapy-induced neurocognitive impairment in pediatric patients
细胞凋亡的发育调节作为儿科患者放疗引起的神经认知障碍的可改变驱动因素
  • 批准号:
    10561668
  • 财政年份:
    2020
  • 资助金额:
    $ 9.05万
  • 项目类别:
Identifying targetable apoptotic vulnerabilities for the treatment of AL amyloidosis
确定治疗 AL 淀粉样变性的靶向凋亡脆弱性
  • 批准号:
    10609467
  • 财政年份:
    2020
  • 资助金额:
    $ 9.05万
  • 项目类别:
Developmental regulation of apoptosis as a modifiable driver of radiotherapy-induced neurocognitive impairment in pediatric patients
细胞凋亡的发育调节作为儿科患者放疗引起的神经认知障碍的可改变驱动因素
  • 批准号:
    10371055
  • 财政年份:
    2020
  • 资助金额:
    $ 9.05万
  • 项目类别:
Identifying targetable apoptotic vulnerabilities for the treatment of AL amyloidosis
确定治疗 AL 淀粉样变性的靶向凋亡脆弱性
  • 批准号:
    10376814
  • 财政年份:
    2020
  • 资助金额:
    $ 9.05万
  • 项目类别:
Regulation of apoptotic priming and competence in healthy and cancerous cells
健康细胞和癌细胞中凋亡启动和能力的调节
  • 批准号:
    8918557
  • 财政年份:
    2014
  • 资助金额:
    $ 9.05万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 9.05万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了