Keigi Fujiwara, Ph.D.

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Contact

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, ACVRI - 211 Bailey Road
Rochester, New York 14642

Office: 585 276-9781 (primary)

Lab: 585 276-9835

Fax: 585 276-9829

Portrait

Research Overview

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.

Education
BA Biology International Christian University, Tokyo, Japan 1968
Ph.D. Biology University of Pennsylvania 1974
Post-Doctoral Training & Residency
Harvard Medical School, Department of Anatomy, Laboratory of Dr. Thomas D. Pollard 1974 - 1977
Fellowship Awards
Harvard Medical School, Muscular Dystrophy Association (stipend and research fund) 1975 - 1977
University of Pennsylvania, Teaching Fellowship (tuition and stipend) 1969 - 1974
Japanese Government Special Scholarship (tuition and stipend) 1967 - 1968
Japanese Government Scholarship (tuition) 1964 - 1966

Lab Description

Mechanosignaling by vascular endotehlial cells. Mechanical forces such as fluid flow & stretch trigger unique responses in endothelial cells, indicating they are capable of sensing mechanical forces.


Lab Website

http://www.urmc.rochester.edu/cvri/research/fujiwara-lab.cfm


Recent Journal Articles
Showing the 5 most recent journal articles. (77 available)
Chiu, Y-J.; McBeath, E.; Fujiwara, K. "Mechanotransduction in an extracted cell model: Fyn drives stretch and flow-elicited PECAM-1 phosphoryaltion." J Cell Biol 182 (2008): 753-763.
Kusano, K.; Thomas, TN.; Fujiwara, K. "Phosphorylation and localization of protein-zero related (PZR) in cultured endothelial cells." Endothelium 15 (2008): 127-136.
Miano JM; Long X; Fujiwara K. "Serum response factor: master regulator of the actin cytoskeleton and contractile apparatus." American journal of physiology. Cell physiology. 2007; 292(1):C70-81. Epub 2006 Aug 23.
Shi F; Chiu YJ; Cho Y; Bullard TA; Sokabe M; Fujiwara K. "Down-regulation of ERK but not MEK phosphorylation in cultured endothelial cells by repeated changes in cyclic stretch." Cardiovascular research. 2007; 73(4):813-22. Epub 2006 Dec 23.
Berk BC; Fujiwara K; Lehoux S. "ECM remodeling in hypertensive heart disease." The Journal of clinical investigation. 2007; 117(3):568-75.