The Role of Telomeres in Lung Transplant Recipient Immunity and Outcomes

端粒在肺移植受者免疫和结果中的作用

基本信息

项目摘要

Project Summary Lung transplantation (LTx) is the only therapeutic option for patients with end-stage lung disease and idiopathic pulmonary fibrosis (IPF) is the most common indication in North America. However, IPF lung transplant recipients (IPF-LTRs) have worse transplant survival compared to all other lung diseases. Mutations in the genes responsible for telomere maintenance are the most common identifiable cause of IPF and our group recently showed that lung transplantation enriches for patients with telomere-mediated disease with as many as a quarter of patients having an identifiable rare variant. Patients with defects in telomere-maintenance genes have an array of immunologic abnormalities that render them susceptible to viral infections. Despite having a weakened immune system, these patients have been reported to reject donor lungs at similar or faster rates than individuals without telomere-mediated disease. The mechanism responsible for this phenomenon are unknown. Based on our preliminary data, we hypothesize that lung transplantation unmasks a complex syndrome that impacts viral host defense, immunosuppression tolerance and allograft rejection. Further, we hypothesize that impaired adaptive immunity is exacerbated by Cytomegalovirus infection by augmenting immunosenescence, however alloimmune and other immune mechanisms can offset and facilitate lung rejection outcomes in transplant recipients with short telomeres. We have divided our approach into three related and synergistic aims. In Aim 1, we examine the consequences of primary CMV infection in patients with telomere-mediate disease and test if two hits, telomere dysfunction and CMV infection, cooperate to drive immune senescence. In Aim 2, we explore the mechanisms that are responsible for lung rejection in individuals with weakened immune systems. Finally, in Aim 3, we test if our recent findings from the University of Pittsburgh can be replicated and extended in a multi- center group of patients from the Lung Transplant Outcomes Group and examine keep outcomes following lung transplantation when stratified by genetic findings and telomere length. We expect that these studies will help improve care and outcomes in patients with telomere-mediated disease.
项目总结

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 }}

Jonathan K. Alder其他文献

348. Kruppel-Like Factor 4 Regulates Proliferation of Human and Mouse Hematopoietic Stem-Progenitor Cells, but Is Not Essential for Mouse Hematopoietic Repopulation
  • DOI:
    10.1016/j.ymthe.2006.08.406
  • 发表时间:
    2006-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jonathan K. Alder;Robert W. Georgantas;Richard L. Hildreth;Curt I. Civin
  • 通讯作者:
    Curt I. Civin

Jonathan K. Alder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('Jonathan K. Alder', 18)}}的其他基金

Mechanisms of Telomere-Mediated Lung Disease
端粒介导的肺部疾病的机制
  • 批准号:
    10445011
  • 财政年份:
    2018
  • 资助金额:
    $ 72.35万
  • 项目类别:
Mechanisms of Telomere-Mediated Lung Disease
端粒介导的肺部疾病的机制
  • 批准号:
    10206235
  • 财政年份:
    2018
  • 资助金额:
    $ 72.35万
  • 项目类别:
Mechanisms of Teleomere-Mediated Emphysema
端粒介导的肺气肿的机制
  • 批准号:
    8819562
  • 财政年份:
    2014
  • 资助金额:
    $ 72.35万
  • 项目类别:
Mechanisms of Teleomere-Mediated Emphysema
端粒介导的肺气肿的机制
  • 批准号:
    9752945
  • 财政年份:
    2014
  • 资助金额:
    $ 72.35万
  • 项目类别:
Mechanisms of Teleomere-Mediated Emphysema
端粒介导的肺气肿的机制
  • 批准号:
    8803454
  • 财政年份:
    2014
  • 资助金额:
    $ 72.35万
  • 项目类别:
Mechanisms of Teleomere-Mediated Emphysema
端粒介导的肺气肿的机制
  • 批准号:
    9081635
  • 财政年份:
    2014
  • 资助金额:
    $ 72.35万
  • 项目类别:
Mechanisms of Teleomere-Mediated Emphysema
端粒介导的肺气肿的机制
  • 批准号:
    8484871
  • 财政年份:
    2012
  • 资助金额:
    $ 72.35万
  • 项目类别:
Mechanisms of Teleomere-Mediated Emphysema
端粒介导的肺气肿的机制
  • 批准号:
    8280746
  • 财政年份:
    2012
  • 资助金额:
    $ 72.35万
  • 项目类别:

相似国自然基金

靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    0 万元
  • 项目类别:
    面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
  • 批准号:
    2023JJ50274
  • 批准年份:
    2023
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
  • 批准号:
    n/a
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
  • 批准号:
    81973577
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
  • 批准号:
    81602908
  • 批准年份:
    2016
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
  • 批准号:
    81501928
  • 批准年份:
    2015
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政​​策的情绪动态
  • 批准号:
    10108433
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
  • 批准号:
    MR/X032809/1
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
  • 批准号:
    MR/X034690/1
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Fellowship
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341426
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341424
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Continuing Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
  • 批准号:
    2335955
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Standard Grant
The economics of (mis)information in the age of social media
社交媒体时代(错误)信息的经济学
  • 批准号:
    DP240103257
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Discovery Projects
How age & sex impact the transcriptional control of mammalian muscle growth
你多大
  • 批准号:
    DP240100408
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Discovery Projects
Supporting teachers and teaching in the age of Artificial Intelligence
支持人工智能时代的教师和教学
  • 批准号:
    DP240100111
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Discovery Projects
Enhancing Wahkohtowin (Kinship beyond the immediate family) Community-based models of care to reach and support Indigenous and racialized women of reproductive age and pregnant women in Canada for the prevention of congenital syphilis
加强 Wahkohtowin(直系亲属以外的亲属关系)以社区为基础的护理模式,以接触和支持加拿大的土著和种族育龄妇女以及孕妇,预防先天梅毒
  • 批准号:
    502786
  • 财政年份:
    2024
  • 资助金额:
    $ 72.35万
  • 项目类别:
    Directed Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了