研究方向 / Research Directions

细胞内的分子不是均匀弥散的——它们在何时、何地出现，以及如何被引导到正确的位置，决定了生命过程的精度与效率。我们实验室长期关注一个核心问题：细胞内的生物分子如何找到自己的目的地。围绕这一主线，我们聚焦 RNA 的亚细胞定位、无膜凝聚体与有膜细胞器的界面互作，以及这些动态过程如何塑造基因表达与天然免疫信号转导，并探索其在疾病中的作用机制。

Molecules inside a cell are not uniformly dispersed. When and where they appear, and how they are guided to their correct destinations, ultimately determine the precision and efficiency of cellular life. Our laboratory is driven by one central question: how do biomolecules inside the cell find their way to the right place? Driven by this overarching question, we study the subcellular localization of RNA, the interplay between membraneless condensates and membrane-bound organelles, and how these dynamic processes shape gene expression and innate immune signaling—as well as how their dysregulation contributes to disease.

一、细胞核内 mRNA 的定向运输机制

I. Directed mRNA Transport within the Nucleus

mRNA 的功能命运始于细胞核。长期以来，mRNA 在核内从转录位点到核孔的运动被默认为随机扩散的结果。我们近期的工作提示，核内存在一类具有明确方向性的 mRNA 运输过程，这意味着细胞核内部可能存在一套尚未被充分认识的空间组织与运输机制。

The functional fate of an mRNA begins in the nucleus. For decades, the movement of mRNA from transcription sites to nuclear pores has been viewed as the outcome of random diffusion. Our recent work suggests otherwise: a subset of nuclear mRNAs undergoes movement with clear directionality, pointing to a spatial organization and transport machinery inside the nucleus that remains largely uncharacterized.

围绕这一线索，我们关注（Guided by this observation, we focus on）：

· 核内定向运输的动力学特征（Dynamics of directed nuclear transport）： 哪些 mRNA 经历定向运输？其运动轨迹、速度与方向性如何被描述与分类？ (Which mRNAs undergo directed transport, and how can their trajectories, velocities, and directionality be quantitatively described and classified?)

· 运输机制的分子基础（Molecular basis of the transport machinery）： 哪些顺式元件、RNA 结合蛋白及无膜核区室（如核斑）参与其中？是否存在支持定向运输的核内结构性框架与动力来源？ (Which cis-elements, RNA-binding proteins, and membraneless nuclear compartments (such as nuclear speckles) are involved? Does a structural framework and an associated motive force exist within the nucleus to support this transport?)

· 运输失调的病理后果（Pathological consequences of transport dysregulation）： 当这一运输机制在癌症、神经退行性疾病等背景下失衡时，会产生怎样的基因表达与细胞功能后果？ (How does disruption of nuclear mRNA transport contribute to altered gene expression and cellular dysfunction in diseases such as cancer and neurodegeneration?)

我们希望通过这一方向，重新定义细胞核作为一个高度组织化的运输空间，并拓展人们对核内分子运动规律的基本认识。 Through this direction, we aim to redefine the nucleus as a highly organized transport environment and to broaden the fundamental understanding of how molecules move within it.

二、凝聚体-细胞器界面在天然免疫中的空间调控

II. Spatial Regulation of Innate Immunity at Condensate–Organelle Interfaces

天然免疫通路的一个显著特征，是与特定细胞器的紧密耦联——cGAS–STING 通路依赖内质网，RNA 感知通路中的 MAVS 锚定于线粒体。与此同时，相分离凝聚体为细胞提供了一种快速、可逆、可动态重组的分子组织方式。我们认为，凝聚体与有膜细胞器之间的界面，很可能是天然免疫实现信号特异性、阈值控制与通路分隔的关键场所，而 RNA 在其中往往同时扮演信号分子与结构支架的双重角色。

A defining feature of innate immune pathways is their tight coupling to specific organelles—STING at the endoplasmic reticulum in the cGAS–STING pathway, and MAVS at mitochondria in RNA-sensing pathways. At the same time, phase-separated condensates provide cells with a rapid, reversible, and dynamically reconfigurable mode of molecular organization. We propose that the interface between condensates and membrane-bound organelles is a critical site where innate immunity achieves signal specificity, threshold control, and pathway segregation, with RNA often serving a dual role as both a signaling molecule and a structural scaffold.

围绕这一界面，我们关注（At this interface, we focus on）：

· 界面凝聚体的形成原理（Formation of interface condensates）： 天然免疫激活过程中，凝聚体如何在特定细胞器表面定向形成？膜-凝聚体界面的分子组成与动态如何被调控？ (How are condensates recruited to specific organelle surfaces during innate immune activation? What regulates the composition and dynamics of the membrane–condensate interface?)

· RNA 介导的时空调控（RNA-mediated spatiotemporal regulation）： RNA 在界面凝聚体中如何决定信号的放大、激活阈值以及不同通路之间的时空分隔？ (How does RNA within interface condensates shape signal amplification, activation thresholds, and the spatial and temporal segregation of distinct immune pathways?)

· 稳态失衡的疾病意义（Disease relevance of interface dysregulation）： 这些界面凝聚体的失调如何驱动慢性干扰素激活相关的自身免疫疾病，或促成肿瘤的免疫逃逸？ (How does dysregulation of these interface condensates drive autoimmune conditions associated with chronic interferon activation, or contribute to tumor immune evasion?)

通过这一方向，我们希望揭示凝聚体与细胞器协作作为天然免疫空间调控的一项基本原则，并为相关疾病的机制理解与干预提供新的思路。 Through this direction, we aim to establish condensate–organelle cooperation as a fundamental principle of spatial regulation in innate immunity, and to open new avenues for understanding and intervening in related diseases.