January 14, 2025

CPOD Faculty Publication Spotlight - King Lab

Chen D, Tang Y, Lapinski P E, Wiggins D, Sevick E M, Davis M J, King P D. Circulation Research. 18 October 2024. EPHB4-RASA1 Inhibition of PIEZ01 Ras Activation Drives Lymphatic Valvulogenesis.
"The Ephrin B4 (EPHB4) growth factor receptor, the RASA1 Ras GTPase-activating protein, and the PIEZO1 mechanoreceptor are each necessary for the development of intraluminal lymphatic vessel valves. Through analysis of genetically engineered mouse models, the King Laboratory now demonstrates that EPHB4 and RASA1 cooperate to limit PIEZO1-induced activation of the Ras-MAPK pathway in valve-forming lymphatic endothelial cells (LEC). Without a functional EPHB4-RASA1 inhibitory mechanism, excessive Ras-MAPK activation in LEC in response to oscillatory shear stress impairs lymphatic valvulogenesis. Findings provide a mechanistic explanation for the frequent identification of inactivating mutations in EPHB4, RASA1, and PIEZO1 genes in human lymphatic vessel diseases and point to means of treatment for these debilitating conditions."
Pictured in center: Dr. Philip D. King, Ph.D. (Professor, Microbiology and Immunology, University of Michigan) with members of his lab.