RESUBMISSION -R01 AI120622 –Restoration of Immunity and Function with DAA Treatment in HCV infection

重新提交 -R01 AI120622 — 使用 DAA 治疗 HCV 感染恢复免疫和功能

基本信息

  • 批准号:
    9246766
  • 负责人:
  • 金额:
    $ 38.88万
  • 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:
    2017-02-14 至 2021-01-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Chronic HCV infection afflicts 180 million individuals throughout the world. The majority of individuals infected with HCV develop persistence, suggesting that HCV successfully subverts innate and adaptive immune responses. Mathematical models have projected a massive increase in the number of patients developing HCV-related complications (e.g., cirrhosis, hepatocellular carcinoma) in the next few decades as the population ages. Although hepatocytes comprise the majority of the total cell population within the liver, the non- parenchymal liver cells have been increasingly recognized as playing central roles in chronic inflammation and complications from HCV infection. Although the development of direct-acting antivirals (DAAs) has led to nearly miraculous cure rates [compared to interferon (IFN)-based therapy], a number of important questions remain unanswered that demand further study. To what extent is immunity restored in patients cured with DAAs and what are the effects on cross-talk between the multiple cell types within the hepatic microenvironment? What effect does HCV cure have on inflammation, fibrosis development, and further hepatic decompensation? The answers to these questions have remained elusive and have implications for other liver disease. Here, we will define the breadth and pace of reconstitution of hepatic and peripheral innate and adaptive immunity induced by DAA therapy in patients with chronic HCV infection. We will also determine how DAA-mediated viral eradication affects epigenetic reprogramming of HCV-specific CTLs. A large cohort of already-enrolling patients, including those who have previously failed DAA therapy and have evidence of resistance-associated variants, will be serially studied according to pre-treatment viral level and fibrosis stage. Next, we will characterize the complex communication between hepatocytes and nonparenchymal cells (NPCs) in HCV infection and the impact of DAA-mediated viral elimination. We hypothesize that exosomes play important roles in intercellular communication that is intricately linked to the cell origin of the exosomes, as well as the biologic milieu; exosomes can shuttle HCV and biologically active molecules from infected hepatoma cells to a variety of NPC. We will examine how purified exosomes derived from HCV-infected and DAA-cured hepatocytes differentially trigger responses in Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs) and HSCs. We will comprehensively characterize the exosomal content following HCV exposure and determine which components, including microRNAs, either amplify or attenuate inflammatory or fibrotic pathways. If successful, these studies would provide novel insights into the mechanisms mediating viral clearance, residual inflammation, and liver injury (fibrosis) and have broad-reaching relevance in the rapidly changing field of HCV, potentially opening up new avenues of research into this highly prevalent liver disease worldwide.
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 }}

HUGO Ramon ROSEN其他文献

HUGO Ramon ROSEN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('HUGO Ramon ROSEN', 18)}}的其他基金

Mechanisms of Advanced NAFLD Disparities in Hispanics: A Multi-level Analysis
西班牙裔晚期 NAFLD 差异的机制:多层次分析
  • 批准号:
    10155155
  • 财政年份:
    2021
  • 资助金额:
    $ 38.88万
  • 项目类别:
Innate Immunity, Cholesterol, and NASH Pathogenesis
先天免疫、胆固醇和 NASH 发病机制
  • 批准号:
    9886092
  • 财政年份:
    2020
  • 资助金额:
    $ 38.88万
  • 项目类别:
Innate and Adaptive Immunity to HCV in Human Pregnancy
人类妊娠期对 HCV 的先天性和适应性免疫
  • 批准号:
    9696625
  • 财政年份:
    2018
  • 资助金额:
    $ 38.88万
  • 项目类别:
Novel Aspects of Hepatic Innate and Adaptive Immunity to HCV Infection
肝脏对 HCV 感染的先天性和适应性免疫的新特点
  • 批准号:
    8633959
  • 财政年份:
    2014
  • 资助金额:
    $ 38.88万
  • 项目类别:
Hepatitis C viral sensing by non-parenchymal liver cells (NPC)
非实质肝细胞 (NPC) 感知丙型肝炎病毒
  • 批准号:
    8583255
  • 财政年份:
    2013
  • 资助金额:
    $ 38.88万
  • 项目类别:
Hepatitis C viral sensing by non-parenchymal liver cells (NPC)
非实质肝细胞 (NPC) 感知丙型肝炎病毒
  • 批准号:
    8662190
  • 财政年份:
    2013
  • 资助金额:
    $ 38.88万
  • 项目类别:
HEPATITIS C VIRAL INFECTION IN HUMAN PREGNANCY
人类妊娠期丙型肝炎病毒感染
  • 批准号:
    8535990
  • 财政年份:
    2012
  • 资助金额:
    $ 38.88万
  • 项目类别:
Midcareer Investigator Award in Patient-Oriented Research (K24)
以患者为导向的研究中的职业中期研究者奖 (K24)
  • 批准号:
    8497578
  • 财政年份:
    2009
  • 资助金额:
    $ 38.88万
  • 项目类别:
Midcareer Investigator Award in Patient-Oriented Research (K24)
以患者为导向的研究中的职业生涯中期研究者奖 (K24)
  • 批准号:
    8305732
  • 财政年份:
    2009
  • 资助金额:
    $ 38.88万
  • 项目类别:
Functional attributes of CD8+ T cells in recovery of hepatitis C virus infection
CD8 T 细胞在丙型肝炎病毒感染恢复中的功能特性
  • 批准号:
    7782728
  • 财政年份:
    2009
  • 资助金额:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 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:
    $ 38.88万
  • 项目类别:
    Directed Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了