Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction

无效的伤口愈合反应会导致慢性辐射引起的唾液腺功能障碍

基本信息

  • 批准号:
    10678634
  • 负责人:
  • 金额:
    $ 34.71万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-20 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Abstract: More than 73% of head and neck cancer patients continue to suffer from the chronic consequences of xerostomia months to years after the completion of radiotherapy making this one of the most compelling issues in salivary gland biology. Despite technological advancements in cancer therapies, collateral damage to salivary glands remains a significant problem for these patients and severely diminishes their quality of life. The field of radiation-induced salivary gland damage is severely hampered by the lack of a comprehensive model detailing the molecular stages of damage. The overall vision is to restore salivary gland function in patients following radiotherapy by identifying healing stages in salivary glands that lead to the stratification and administration of precise therapeutics for their stage. This proposal will use the sequential phases of wound healing involving inflammation to its resolution and reconstitution of tissue through proliferation and differentiation of epithelial tissue as steps to accomplish this vision. We hypothesize that irradiated salivary glands fail to efficiently progress through the wound healing phases leading to prolonged dysfunction. Our prior work has demonstrated that radiation-induced proliferation in salivary glands is due in part to disruption of the PKCζ apical polarity complex leading to enhanced nuclear localization of Yap, while models that restore salivary function have repaired apical polarity and reduced nuclear localization of Yap. We propose to develop a model that integrates each phase of wound healing detailing the interactions between phases and the impact of nuclear Yap on the progression through these phases. The outcomes from this work include: 1) inputs regulating sustained Yap nuclear translocation, 2) ability of chronic nuclear Yap to prevent re-differentiation after IR, 3) when/if Yap is necessary for restoration of salivary gland function, 4) uncovering the interplay between wound healing phases that prevent restoration of salivary gland function. Understanding this process would have a positive impact by revealing intervention points that promote restoration of salivary gland function.
抽象的: 超过 73% 的头颈癌患者继续遭受以下慢性后果的困扰 放疗完成后数月至数年的口干症使其成为最引人注目的问题之一 唾液腺生物学问题。尽管癌症治疗技术取得了进步,但附带条件 唾液腺损伤对于这些患者来说仍然是一个重大问题,并且严重减少 他们的生活质量。辐射引起的唾液腺损伤领域受到以下因素的严重阻碍: 缺乏详细描述损伤分子阶段的综合模型。总体愿景是 通过识别唾液的愈合阶段来恢复放疗后患者的唾液腺功能 腺体导致针对其阶段的精确治疗的分层和管理。这 该提案将利用涉及炎症的伤口愈合的连续阶段来解决问题, 通过上皮组织的增殖和分化来重建组织 实现这一愿景。我们假设受辐射的唾液腺无法有效进展 通过伤口愈合阶段导致长期功能障碍。我们之前的工作已经证明 放射诱导的唾液腺增殖部分是由于 PKC z 顶端的破坏 极性复合物导致 Yap 的核定位增强,而恢复唾液的模型 功能修复了顶端极性并减少了 Yap 的核定位。我们建议开发 整合了伤口愈合的每个阶段的模型,详细说明了阶段和阶段之间的相互作用 核 Yap 对这些阶段进展的影响。这项工作的成果 包括:1) 调节持续 Yap 核易位的输入,2) 慢性核 Yap 的能力 防止 IR 后的再分化,3) 当/如果 Yap 对于恢复唾液腺功能是必需的, 4)揭示阻碍唾液腺恢复的伤口愈合阶段之间的相互作用 功能。了解这一过程将通过揭示干预点产生积极影响 促进唾液腺功能的恢复。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Evaluating the transcriptional landscape and cell-cell communication networks in chronically irradiated parotid glands.
  • DOI:
    10.1016/j.isci.2023.106660
  • 发表时间:
    2023-05-19
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    Rheinheimer, Brenna A.;Pasquale, Mary C.;Limesand, Kirsten H.;Hoffman, Matthew P.;Chibly, Alejandro M.
  • 通讯作者:
    Chibly, Alejandro M.
{{ 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 }}

KIRSTEN H LIMESAND其他文献

KIRSTEN H LIMESAND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('KIRSTEN H LIMESAND', 18)}}的其他基金

Metabolic dysregulation during radiation-induced salivary gland dysfunction
辐射引起的唾液腺功能障碍期间的代谢失调
  • 批准号:
    10254415
  • 财政年份:
    2020
  • 资助金额:
    $ 34.71万
  • 项目类别:
Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction
无效的伤口愈合反应会导致慢性辐射引起的唾液腺功能障碍
  • 批准号:
    10221671
  • 财政年份:
    2019
  • 资助金额:
    $ 34.71万
  • 项目类别:
Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction
无效的伤口愈合反应会导致慢性辐射引起的唾液腺功能障碍
  • 批准号:
    10022119
  • 财政年份:
    2019
  • 资助金额:
    $ 34.71万
  • 项目类别:
Ineffective wound healing responses enable chronic radiation-induced salivary gland dysfunction
无效的伤口愈合反应会导致慢性辐射引起的唾液腺功能障碍
  • 批准号:
    10457942
  • 财政年份:
    2019
  • 资助金额:
    $ 34.71万
  • 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的拯救辐射引起的唾液腺功能障碍的机制
  • 批准号:
    7900030
  • 财政年份:
    2008
  • 资助金额:
    $ 34.71万
  • 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的放射诱导唾液腺功能障碍的挽救机制
  • 批准号:
    7530790
  • 财政年份:
    2008
  • 资助金额:
    $ 34.71万
  • 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的拯救辐射引起的唾液腺功能障碍的机制
  • 批准号:
    8288027
  • 财政年份:
    2008
  • 资助金额:
    $ 34.71万
  • 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的放射诱导唾液腺功能障碍的挽救机制
  • 批准号:
    7879108
  • 财政年份:
    2008
  • 资助金额:
    $ 34.71万
  • 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的放射诱导唾液腺功能障碍的挽救机制
  • 批准号:
    8111787
  • 财政年份:
    2008
  • 资助金额:
    $ 34.71万
  • 项目类别:
Mechanisms of IGF-1 mediated rescue of radiation-induced salivary gland dysfuncti
IGF-1介导的放射诱导唾液腺功能障碍的挽救机制
  • 批准号:
    7663151
  • 财政年份:
    2008
  • 资助金额:
    $ 34.71万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 34.71万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了