Metabolic regulation of exosome biogenesis

外泌体生物发生的代谢调节

• 批准号: 10668526
• 负责人: Sangmoo Jeong
• 金额: $ 40.94万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10668526
• 关键词: Address; Biogenesis; Biological Markers; Blood; Brain Injuries; Cell membrane; Cell secretion; Cells; Clinical Treatment; Clinical Trials; Detection; Diagnosis; Diagnostic; Diameter; Disease; Future; Generations; Goals; Mesenchymal Stem Cells; Metabolic; Metabolism; Mitochondria; Molecular; Monitor; Natural regeneration; Nutrient; Production; Proteins; RNA; Regulation; Research; Role; Sorting; Stress; Technology; Testing; Therapeutic; Therapeutic Agents; Urine; Vesicle; cell type; clinical application; exosome; extracellular vesicles; immunoregulation; microvesicles; nanoscale

Project Summary/Abstract Exosomes are nanoscale vesicles with a diameter of 50-200 nm, actively secreted by various types of cells in our body. As they carry biomolecules (e.g., proteins, RNAs, or metabolites) specific to their parental cells and are easily found in biofluids (e.g., blood or urine), exosomes have emerged as a promising biomarker for the detection and treatment monitoring of various diseases. Also, exosomes have the strong potential as a therapeutic agent for regeneration and immune regulation; for example, exosomes from mesenchymal stem cells (MSCs) have been tested in clinical trials for the treatment of brain injury. However, the fundamental mechanisms of what makes cells secrete exosomes and how the molecular contents in exosomes are determined remain unclear; for example, we have limited information about how to regulate MSCs to maximize the production of their exosomes carrying therapeutic molecules. My Lab aims to address these questions by investigating the role of metabolism in exosome biogenesis, because multiple steps of exosome biogenesis, including vesicle formation inside a cell and fusing into the plasma membrane, are directly associated with metabolic processes. In this Project, we will investigate how the exosome generation rate and molecular contents are determined under different metabolic conditions, specifically with the modulation of nutrients and NAD levels. We will also develop a single exosome sorting technology based on intravesicular proteins and investigate the biogenesis of exosomes with mitochondrial molecules under mitochondrial stress conditions. The research accomplishments from this Project will deepen our understanding of exosomes and help us develop exosome-based diagnostic and therapeutic strategies more effectively. Our long-term research goal is to identify the mechanisms of the interplay between metabolism and biogenesis of extracellular vesicles (EVs). This MIRA research focuses on exosomes, a subpopulation of EVs. Based on our research progresses, we will expand our research scope to other EVs, including microvesicles, in the future.

项目概要/摘要 外泌体是直径为50-200 nm的纳米级囊泡，由多种类型的细胞主动分泌 我们的身体。因为它们携带亲代细胞特有的生物分子（例如蛋白质、RNA 或代谢物），并且 很容易在生物体液（例如血液或尿液）中找到，外泌体已成为一种有前途的生物标志物 各种疾病的检测和治疗监测。此外，外泌体具有作为 再生和免疫调节治疗剂；例如，来自间充质干细胞的外泌体 细胞（MSC）已在治疗脑损伤的临床试验中进行了测试。然而，基本的 细胞分泌外泌体的机制以及外泌体中的分子含量如何 确定仍不清楚；例如，关于如何监管​​ MSC 以最大限度地发挥作用，我们的信息有限。 产生携带治疗分子的外泌体。我的实验室旨在通过以下方式解决这些问题 研究代谢在外泌体生物发生中的作用，因为外泌体生物发生的多个步骤， 包括细胞内囊泡的形成和融合到质膜中，与 代谢过程。在这个项目中，我们将研究外泌体的生成速率和分子水平如何 含量是在不同的代谢条件下确定的，特别是通过营养物质的调节和 NAD 水平。我们还将开发基于囊泡内蛋白的单一外泌体分选技术和 研究线粒体应激条件下外泌体与线粒体分子的生物发生。 该项目的研究成果将加深我们对外泌体的认识，帮助我们 更有效地开发基于外泌体的诊断和治疗策略。我们的长期研究目标是 确定细胞外囊泡（EV）代谢和生物发生之间相互作用的机制。 MIRA 的这项研究重点是外泌体，即 EV 的一个亚群。根据我们的研究进展，我们将 未来将我们的研究范围扩大到其他电动汽车，包括微泡。