研究方向

细胞生物学教科书中关于细胞间信息通讯的部分通常介绍两种主要方式:一是通过细胞直接接触,二是通过分泌信号分子(如激素、趋化因子、生长素等)至胞外,以实现细胞或组织器官之间的信息传递。然而,如今第三种胞间通讯方式已被广泛认可,并在近十年成为细胞生物学领域的研究热点:即细胞外囊泡/外泌体(Extracellular Vesicle,以下简称EV)介导的生物分子传递。从原核细胞、植物细胞到动物细胞,几乎所有已知类型的细胞都具备分泌和释放EV的机制。在EV生成过程中,细胞内存在复杂的分选机制,可选择性招募并装载特定蛋白质、RNA和代谢分子等进入EV,最终形成直径约70~200纳米的磷脂膜包被囊泡,并释放至细胞外基质。进入组织间隙的EV可能被邻近细胞摄取,也可能进入循环系统并被远端器官吸收。细胞摄取过程涉及多种受体分子的调控,目前普遍认为EV与细胞之间的识别和摄取具有特异性与选择性。EV进入受体细胞后,会释放其携带的货物分子,这些远距离递送的蛋白质和RNA可参与并改变受体细胞的行为及生理状态,从而实现细胞间信息传递。

目前,EV在生物医学及临床转化中仍面临诸多方法学限制。EV researchers 首先需应对的难题是其尺寸极小,约100纳米的直径使得EV的分离与纯化过程复杂而繁琐。此外,对此类微小颗粒的表征几乎超出了光学成像的极限,而EV内容物中低丰度的货物分子也对检测方法的灵敏度提出了极高要求。另一方面,EV的异质性 (EV heterogeneity) 使科学问题更加复杂化。不同细胞来源的EV在膜表面修饰和内容物组成方面差异显著,而从血浆或尿液等样本中采集的EV往往是来源高度异质的混合物。若不进行来源/EV亚群细分,很难获得可靠的诊断标志物。而针对EV亚群的研究受限于方法学不足,进展较为缓慢。

Research Interests

Cells communicate through a variety of mechanisms, traditionally described as either direct cell contact or the secretion of signaling molecules such as hormones, chemokines, and growth factors. In recent years, a third and equally important mode of communication has gained wide recognition—extracellular vesicle (EV)-mediated transfer of biomolecules. EVs are nanosized, membrane-enclosed vesicles (approximately 70–200 nm in diameter) secreted by nearly all cell types across prokaryotic, plant, and animal kingdoms. During their biogenesis, specific proteins, RNAs, and metabolites are selectively packaged into EVs and subsequently released into the extracellular space. These vesicles can be taken up by neighboring or distant cells, where they release their cargo and modulate cellular behavior and physiological states, thus playing critical roles in intercellular communication and disease progression.

Despite their great promise, EV research in biomedical and clinical applications faces several methodological challenges. Their nanoscale size makes isolation, purification, and characterization difficult, while their compositional heterogeneity complicates biomarker discovery and functional studies. Addressing these limitations is central to our laboratory’s mission. Our research focuses on three major directions: