The Jia laboratory is interested in understanding the cellular and molecular mechanisms of embryonic development and organogenesis, especially the circulation system formation. We use zebrafish as the major model system, which is an excellent vertebrate model due to its external and rapid development, optical transparency, convenience for live-cell imaging, and amenability for chemical and forward genetic screens. Additionally, we also use cultured cell lines and mouse model to explore the conserved mechanisms in mammalian systems.

1. The role of phospholipid molecules in early embryo development and organogenesis

As the vital membrane components, phospholipid molecules have been reported to be important for the proper functioning of the nervous, digestive, skeletal, as well as alveolar systems. However, whether phospholipid molecules have more essential roles in embryonic development and organogenesis needs further investigation. We found that endosomal phosphoinositide conversion regulated by PITP family member Sec14l2/Sec14l3 is required for endosome fission, and therefore VEGFR2 trafficking to promote vasculogenesis in zebrafish (Nat Commun, 2019; Nat Cell Biol, 2021). Next, we will focus on the cellular functions of phospholipid molecules by exploring their specific distribution and dynamic conversion in different membrane structures, and finally their possible roles in embryonic development and organogenesis.

2. Lymphatic development and its molecular regulation

Given the importance of lymphatic vasculature in immune responses, tumor metastasis, lymphedema and many other pathological conditions, the long-term goal of our research is to understand the molecular mechanisms of the lymphatic development. Along with the successful discoveries that zebrafish lymphatic system shares many of the morphological, molecular and functional characteristics of lymphatic vessels in mammals, and the generation of transgenic reporter lines as powerful tools for imaging and studying lymphatic development in vivo, using zebrafish to study lymphatic vasculature becomes a reality in recent years. Furthermore, based on the establishment of several lymphatic and complex vascular disease models using zebrafish, we will also make efforts to conduct a whole-organism, phenotype-based, small molecule screening. Our research findings will be likely to provide more treatment clues for human lymphatic and complex vascular diseases.

3. Lymphatic vascular heterogeneity and specialization

Despite sharing a broadly similar origin and molecular mechanisms to form lymphatic ECs during embryonic development, the molecular, morphological and functional heterogeneity within the lymphatic ECs is increasingly recognized in both normal and disease conditions. However, the mechanisms by which lymphatic ECs specialize to fulfil their distinct features are poorly understood. Therefore, we hope to investigate how these differences between lymphatic EC subsets are established and maintained, and how these differences contribute to specific functions of lymphatic vessels in different tissues and organs, as well as in different physiological and pathological states.

    随着近年来对淋巴管重要功能的认识逐渐深入，人们发现在不同组织器官及病理状态下淋巴管可以发挥不同的作用，并且呈现出许多新的功能。例如：在小肠、脑膜和淋巴结中的淋巴管具有不同的形态结构，以及分子特征，发挥着独特的功能。此外，淋巴管还被发现可能在肥胖、炎症性肠病、心血管疾病、青光眼和神经系统等疾病中发挥作用。因此，我们的研究目标是发现在不同组织器官及生理病理状态下，淋巴管是否具有新的功能。同时，寻找不同类群的淋巴管内皮细胞，探究其在细胞来源、分子特征及结构功能上的差异，进而解析淋巴管的异质性及其组织特异性功能发挥的分子基础。