Metabolic regulation of exosome biogenesis

项目总结/摘要 外泌体是直径为50-200 nm的纳米级囊泡，由各种类型的细胞在体内主动分泌。 我们的身体因为它们携带生物分子（例如，蛋白质、RNA或代谢物），以及 很容易在生物流体中发现（例如，血液或尿液），外泌体已经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，外泌体具有强大的潜力， 用于再生和免疫调节的治疗剂;例如，来自间充质干细胞的外来体 干细胞（MSC）已经在临床试验中测试用于治疗脑损伤。但根本 是什么使细胞分泌外泌体的机制以及外泌体中的分子内容物是如何 确定仍然不清楚;例如，我们对如何调节MSC以最大化 产生携带治疗分子的外泌体。我的实验室旨在解决这些问题， 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，直接与 代谢过程在这个项目中，我们将研究外泌体的产生率和分子水平如何影响细胞的生长。 在不同的代谢条件下测定含量，特别是通过调节营养素， 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， 研究在线粒体应激条件下具有线粒体分子的外来体的生物发生。 该项目的研究成果将加深我们对exosomes的理解， 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 以确定细胞外囊泡（EV）的代谢和生物发生之间的相互作用的机制。 这项MIRA研究的重点是外泌体，这是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展到其他电动汽车，包括微泡。

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.