Keigi Fujiwara, Ph.D.
|1974 | Ph.D. | Biology | University of Pennsylvania|
|1968 | Ph.D. | International Christian University, Tokyo, Japan|
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:
- What happens to PECAM-1 when mechanical force is applied to it?
- How is PECAM-1 tyrosine phosphorylated by mechanical force?
- What signaling events are activated by PECAM-1 phosphorylation?, and
- 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.
- Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. Heo KS, Fujiwara K, Abe J. Circ J. 2011;75(12):2722-30. Epub 2011 Nov 10.
- Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart. Miller CL, Cai Y, Oikawa M, Thomas T, Dostmann WR, Zaccolo M, Fujiwara K, Yan C.
Basic Res Cardiol. 2011 Nov;106(6):1023-39. Epub 2011 Oct 20.
- PKCζ mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation. Heo KS, Lee H, Nigro P, Thomas T, Le NT, Chang E, McClain C, Reinhart-King CA, King MR, Berk BC, Fujiwara K, Woo CH, Abe J. J Cell Biol. 2011 May 30;193(5):867-84.
- MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation. Chang E, Heo KS, Woo CH, Lee H, Le NT, Thomas TN, Fujiwara K, Abe J.
Blood. 2011 Feb 24;117(8):2527-37. Epub 2010 Dec 3.
- PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5. Nigro P, Abe J, Woo CH, Satoh K, McClain C, O'Dell MR, Lee H, Lim JH, Li JD, Heo KS, Fujiwara K, Berk BC. Blood. 2010 Sep 16;116(11):1971-9. Epub 2010 Jun 10.
Keigi Fujiwara , Ph.D.
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, CVRI
Rochester, New York 14642
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