Fujiwara Lab

Dr. Fujiwara’s major research is on mechanosignaling by vascular endothelial cells. Mechanical forces such as fluid flow and stretch trigger unique responses in endothelial cells, indicating that they are capable of sensing mechanical forces. However, the molecular mechanism responsible for this interesting ability of the cells is largely unknown. The recent studies by his research group have indicated that that an endothelial cell adhesion molecule, PECAM-1 (also called CD31) and the actin cytoskeleton are involved in this mechanism. When endothelial cells are exposed to a physiological levels of fluid shear stress, PECAM-1 is rapidly phosphorylated at two tyrosine residues, and this tyrosine phosphorylation appears to be one of the earliest protein modification events one can detect in these cells. Interestingly, PECAM-1 can be also tyrosine phosphorylated by tugging force applied directly to the molecule on the cell surface, suggesting that this molecule is mechanoresponsive. At present, following specific questions are being investigated: (1) what happens to PECAM-1 when mechanical force is applied to it?, (2) how is PECAM-1 tyrosine phosphorylated by mechanical force?, (3) what signaling events are activated by PECAM-1 phosphorylation?, and (4) what role does the actin cytoskeleton play in PECAM-1 signaling? To answer these questions, the laboratory uses techniques of molecular and cell biology, structural analyses, and animal models including PECAM-1 KO mice.