Endothelial cell–pericyte crosstalk governs organ homeostasis
The crosstalk between endothelial cells and pericytes is essential for angiogenesis, vessel remodeling, and the maintenance of vascular homeostasis. Dysregulation of endothelial cell–pericyte interactions impairs angiogenesis and vascular integrity, which are hallmark features of various diseases, including cancer, diabetic retinopathy, liver fibrosis, lung edema, autoimmune diseases, and neurodegenerative disorders. Our research focus on systematically mapping the endothelial cell–pericyte interaction landscape in both normal and pathological conditions. By unraveling these mechanisms, we aim to develop targeted therapies that restore the disrupted endothelial cell-pericyte interactions driving these diseases, offering innovative treatment strategies where conventional approaches fall short.
Publications: Yang et. al., Hepatology, 2021 | He et. al., Journal of Experimental Medicine, 2023 | Zhu et. al., The EMBO Journal, 2024
Vessel lumen size determination and maintenance
The lumen size of mature blood vessels is quite stable; however, it could undergo vessel remodeling under certain conditions, such as the enlargement of collateral vessels that connect the ischemic tissue. It is well accepted that both the blood flow and the metabolic demand of surrounding tissue play important roles in determining vessel size. However, whether there exist intrinsic pathways that actively control a vessel’s lumen size remains elusive. We are currently utilizing a microfluidic-based vessel formation system and genetic mouse models to explore the endothelial cell-intrinsic mechanisms that determine and maintain vessel diameter.
Publication: Zhang et. el., Arteriosclerosis, Thrombosis, and Vascular Biology, 2022
Novel mechanisms that regulate endothelial inflammatory responses
Endothelium serve as a primary interface between the blood and tissues. Upon inflammation, endothelial cells upregulate the expression of cytokines, chemokines, and adhesion molecules, which facilitate the recruitment and extravasation of immune cells into inflammatory sites. We are currently investigating novel mechanisms that regulate endothelial inflammatory response independent of the NF-κB pathway. In addition, we are collaborating with medicinal chemists in the development of novel small molecules that could specifically reduce the inflammatory responses in endothelial cells for the treatment of many inflammatory diseases.
Publication: Dai et. el., Cell Death and Disease, 2020