Description of Research Expertise

Research Interests
Signaling pathways in angiogenesis and hemostasis.

Key words: Angiogenesis, vascular development, platelet, signaling.

Description of Research
My laboratory investigates signaling pathways in cardiovascular development and function. We have two general areas of interest: angiogenesis and platelet signaling. In some cases these areas intersect, e.g. the role of Syk and SLP-76 signaling downstream of platelet receptors that regulate lymphatic vascular development. Major projects in the lab include the following: Regulation of lymphatic vascular development by Syk and SLP-76 signaling. Mice lacking Syk or SLP-76 exhibit lethal vascular phenotypes that we have recently found to be due to a failure to separate emerging lymphatic vessels from pre-existing blood vessels. We have recently identified platelet interaction with lymphatic endothelial cells as the basis for this mechanism of vascular regulation. The long term goals of this project are to understand how platelets control endothelial function and lymphatic vascular development. Platelet immunoreceptor signaling. There are two platelet-specific immune-type receptors, GPVI and CLEC2, that activate Syk and SLP-76 signals. GPVI is a collagen receptor that functions in hemostasis and thrombosis. CLEC2 is a receptor for the lymphatic endothelial protein PDPN and regulates blood-lymphatic vascular interactions. We are presently using mouse genetic models to understand how these two receptors signal and to define their biological roles in vivo. Role of cerebral cavernous malformation (CCM) signaling pathway in vascular development and disease. CCMs are a common human vascular disease caused by loss of function mutations in 3 CCM proteins. We have recently shown that the Heart of Glass (HEG) receptor and CCM proteins are required in mouse and fish cardiovascular development. We are actively investigating how this recently identified pathway regulates endothelial function in development and causes CCMs.

Rotation Projects
1. Regulation of lymphatic vascular development by platelet signaling. 2. HEG-CCM signaling in fish and mouse models. 3. Novel receptor signaling pathways in mammalian cardiovascular development. 4. Development and application of lymphatic endothelial-specific gene knockouts.

Lab personnel:
Xiangjain Zheng, PhD-postdoctoral fellow; Zhiyng Zou, PhD-postdoctoral fellow; Cara Bertozzi, PhD student; Chiu-Yu Chen, MD-PhD student; Alec Schmaier, PhD student; Chong Xu, PhD-postdoctoral fellow; Jiping Xiao, PhD-postdoctoral fellow; Patricia Mericko, Lab Manager; Mei Chen Research, Specialist.