Xiaolei Su, PhD

Project Title: Fractalkine signaling in liver sinusoidal endothelial cells

In response to tissue infection or injury, circulating leukocytes migrate across the endothelial layers to reach the tissue to eliminate pathogens, promote wound healing, or regulate local inflammatory responses. Transendothelial migration occurs in two paths, either at the junction between endothelial cells (paracellular) or through endothelial cells (transcellular). Comparing to paracellular migration, which involves the opening of tight-junctions, transcellular migration was considered to better maintain the integrity of endothelial layer although it remains unclear how endothelial cells remodel their membrane and cytoskeleton to create tunnels to accommodate the penetration of leukocytes. Liver sinusoidal endothelial cells (LSECs) present a preferred model for investigating transcellular migration because it was observed at high frequency in LSECs. Importantly, LSECs play a critical role in regulating the number and activation of infiltrating leukocytes although the underlying mechanism is poorly understood. In this proposal, we aim to delineate the signaling pathway that promotes transcellular migration in LSECs. Biochemical reconstitution, high-resolution microscopy, together will cell engineering approaches will be implemented. This work is expected to identify a novel receptor, FKN, that promotes transcellular migration through LSECs. It will provide molecular insights into understanding the causes of inflammation-related liver injury.