In Vivo Regulated Release and Function of Extracellular Small RNAs

细胞外小 RNA 的体内调节释放和功能

基本信息

项目摘要

DESCRIPTION (provided by applicant): There is a desperate need for new means to diagnose and treat most human diseases. Extracellular small RNAs provide great promise. In particular, recent findings provide strong evidence for their utility as biomarkers. Furthermore, very recent work shows functional roles for at least a subset of the extracellular small RNAs, which provides an opportunity for their manipulation in the treatment of disease. However, as the field is so recent with only anecdotal evidence in limited systems, there remains a fundamental gap in our knowledge of how wide spread the phenomenon of functional extracellular small RNAs really is and how can its potential be fully realized. This U19 Center's long-term goal is to uncover paradigms of extracellular small RNA function in health and disease and apply those paradigms to clinically relevant settings including biomarker discovery and therapeutic intervention. Members of the Center already have a significant track record in these areas. The objective here is to delve into the mechanism and role of small non-coding RNA secretion looking for unifying themes across tissues including the immune system, the liver, the prostate, and neural system and across species from C.elegans to mouse to human. The overarching hypothesis is that extracellular small RNAs represents a heterogeneous landscape that ranges from miRNA dumping to active signaling, and which can be differentiated based on the selectivity and form of their release into body fluids. The Center proposes to tackle this hypothesis by integrating the efforts of six principle investigators with expertise in differet types of small non-coding RNAs, in multiple model organisms, in the biochemistry of secretion and metabolism of lipid, and in imaging. The Center will consist of four projects and a scientific core dedicated to the isolation and characterization of lipid-associated and lipid-free forms of extracellular small RNAs. The aims will be to determine the source, the form, the destination, and the function of extracellular small RNAs in four distinct settings: immune stimulation, primary cancer progression, metastatic tumor growth, and olfactory neuron stimulation. Completion of these aims is expected to uncover common paradigms as well as distinct mechanisms reflecting the different drivers across these settings. This U19 Center proposal is highly significant as it will provide a vertical leap in our knowledge of what extracellular small RNAs represent and what their downstream functions are. This knowledge will enable improved insights into how to use extracellular small RNAs to follow disease and how to manipulate their levels in order to treat disease.
描述(由申请人提供):迫切需要新的手段来诊断和治疗大多数人类疾病。细胞外小rna提供了巨大的希望。特别是,最近的发现为它们作为生物标志物的效用提供了强有力的证据。此外,最近的研究表明,至少一部分细胞外小rna具有功能作用,这为它们在疾病治疗中的操纵提供了机会。然而,由于该领域是如此的新,在有限的系统中只有轶事证据,我们对功能性细胞外小rna现象的广泛传播以及如何充分实现其潜力的认识仍然存在根本性的差距。U19中心的长期目标是揭示细胞外小RNA在健康和疾病中的功能模式,并将这些模式应用于临床相关设置,包括生物标志物发现和治疗干预。该中心的成员在这些领域已经有了重要的记录。这里的目标是深入研究小非编码RNA分泌的机制和作用,寻找跨组织的统一主题,包括免疫系统、肝脏、前列腺和神经系统,以及从秀丽隐杆线虫到小鼠到人类的跨物种。总体假设是,细胞外小rna代表了从miRNA倾销到活性信号传导的异质景观,并且可以根据其释放到体液中的选择性和形式进行区分。该中心建议通过整合六名主要研究人员在不同类型的小非编码rna、多种模式生物、脂质分泌和代谢的生物化学以及成像方面的专业知识来解决这一假设。该中心将由四个项目和一个科学核心组成,致力于分离和表征脂质相关和无脂质形式的细胞外小rna。目的是确定细胞外小rna在四种不同情况下的来源、形式、目的地和功能:免疫刺激、原发性癌症进展、转移性肿瘤生长和嗅觉神经元刺激。这些目标的完成有望揭示共同的范例以及反映这些设置中不同驱动因素的独特机制。这个U19中心的提议非常重要,因为它将为我们了解细胞外小rna代表什么以及它们的下游功能提供一个垂直飞跃。这些知识将使我们能够更好地了解如何使用细胞外小rna来跟踪疾病,以及如何操纵它们的水平以治疗疾病。

项目成果

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Robert Blelloch其他文献

Robert Blelloch的其他文献

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{{ truncateString('Robert Blelloch', 18)}}的其他基金

Establishing the development basis for the morphological and functional asymmetry of the human chorion
建立人类绒毛膜形态和功能不对称的发育基础
  • 批准号:
    10673397
  • 财政年份:
    2023
  • 资助金额:
    $ 145.33万
  • 项目类别:
Mechanisms of Exosome Driven Immunoregulation of Cancer Progression
外泌体驱动的癌症进展免疫调节机制
  • 批准号:
    10381379
  • 财政年份:
    2021
  • 资助金额:
    $ 145.33万
  • 项目类别:
Mechanisms of Exosome Driven Immunoregulation of Cancer Progression
外泌体驱动的癌症进展免疫调节机制
  • 批准号:
    10671960
  • 财政年份:
    2019
  • 资助金额:
    $ 145.33万
  • 项目类别:
Iteratively redefining developmental potential through poised enhancers
通过稳定的增强剂迭代地重新定义发展潜力
  • 批准号:
    9753014
  • 财政年份:
    2017
  • 资助金额:
    $ 145.33万
  • 项目类别:
Rewiring of the pluripotency enhancer network during early mammalian development
早期哺乳动物发育过程中多能性增强子网络的重新布线
  • 批准号:
    9403957
  • 财政年份:
    2017
  • 资助金额:
    $ 145.33万
  • 项目类别:
Rewiring of the pluripotency enhancer network during early mammalian development
早期哺乳动物发育过程中多能性增强子网络的重新布线
  • 批准号:
    9754842
  • 财政年份:
    2017
  • 资助金额:
    $ 145.33万
  • 项目类别:
In Vivo Regulated Release and Function of Extracellular Small RNAs
细胞外小 RNA 的体内调节释放和功能
  • 批准号:
    8923178
  • 财政年份:
    2013
  • 资助金额:
    $ 145.33万
  • 项目类别:
In Vivo Regulated Release and Function of Extracellular Small RNAs
细胞外小 RNA 的体内调节释放和功能
  • 批准号:
    9122348
  • 财政年份:
    2013
  • 资助金额:
    $ 145.33万
  • 项目类别:
In Vivo Regulated Release and Function of Extracellular Small RNAs
细胞外小 RNA 的体内调节释放和功能
  • 批准号:
    8713966
  • 财政年份:
    2013
  • 资助金额:
    $ 145.33万
  • 项目类别:
In Vivo Regulated Release and Function of Extracellular Small RNAs
细胞外小 RNA 的体内调节释放和功能
  • 批准号:
    9519087
  • 财政年份:
    2013
  • 资助金额:
    $ 145.33万
  • 项目类别:

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