Department of Biochemistry

Honors

Associate Editor, Biochemistry, 1980-present
Bristol-Myers Squibb Award, 1999
Distinguished Achievement Award, American Heart Association, 1995
Member, American Academy of Arts and Sciences, 1987
Chair, Department of Biochemistry, University of Washington, 1975-1984
Member, National Academy of Sciences, 1980

Research

The research program of Dr. Earl Davie and his group deals primarily with proteins involved in blood coagulation and fibrinolysis. In this research, the structure and function of a number of proteins are studied and their role in the formation of fibrin examined. X-ray diffraction studies are carried out on a recombinant fragment of the gamma chain of human fibrinogen and detailed molecular interactions at the initial stages of fibrin polymerization are examined. Two novel proline-rich gamma-carboxyglutamic acid-containing proteins have been identified by homologous cloning techniques. These proteins are apparently transmembrane proteins with intracellular domains that may participate in signal transduction. Studies to identify ligands for these proteins are in progress. Proteins that bind to regulatory elements in the genes for several coagulation proteins, including fibrinogen, factor VII, factor X and protein C have been identified and cloned. Their role in the regulation of the circulating levels of these proteins in blood will be studied. The physiological role of a protease activated receptor (PAR4) and a novel actin binding protein homologue that binds to platelet GPIßalpha are also being studied.

Selected Publications

Davie EW (2003) A brief historical review of the waterfall/cascade of blood coagulation. J Biol Chem 278, 50819-32.

Chung DW, Fujikawa K (2002) Processing of von Willebrand factor by ADAMTS-13. Biochemistry 41, 11065-70.

Kulman JD, Harris JE, Xie L, Davie EW (2001) Identification of two novel transmembrane gamma-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues. Proc Natl Acad Sci USA 98, 1370-5.

Liu ML, Shen BW, Nakaya S, Pratt KP, Fujikawa K, Davie EW, Stoddard BL, Thompson AR (2000) Hemophilic factor VIII C1- and C2-domain missense mutations and their modeling to the 1.5-angstrom human C2-domain crystal structure. Blood 96, 979-87.

Pratt KP, Shen BW, Takeshima K, Davie EW, Fujikawa K, Stoddard BL (1999) Structure of the C2 domain of human factor VIII at 1.5 A resolution. Nature 402, 439-42

Andersen H, Greenberg DL, Fujikawa K, Xu W, Chung DW, Davie EW (1999) Protease-activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity. Proc Natl Acad Sci USA 96, 11189-93.

Xu W-F, Xie Z-W, Chung DW and Davie EW (1998) A Novel Actin-Binding Protein Homologue that Binds to Platelet Glycoprotein I§alpha. Blood, 92, 1268.

Xu, W-F, Andersen H, Whitmore TE, Gilbert T, Davie EW and Foster D (1998) Cloning and Characterization of a Novel Human Protease-Activated Receptor (PAR4). Proc Natl Acad Sci 95, 6642.

Cote HC, Pratt KP, Davie EW, Chung DW (1997) The polymerization pocket "a" within the carboxyl-terminal region of the gamma chain of human fibrinogen is adjacent to but independent from the calcium-binding site. J Biol Chem 272, 23792.

Kulman, J.D., Harris, J.E., Haldeman, B.A., Davie, E.W (1997) Primary structure and tissue distribution of two novel proline-rich gamma-carboxyglutamic acid proteins. Proc Natl Acad Sci 94, 9058.

Pratt KP, Cote HC, Chung DW, Stenkamp RE, Davie EW (1997) The primary fibrin polymerization pocket: three-dimensional structure of a 30-kDa C-terminal gamma chain fragment complexed with the peptide Gly-Pro-Arg-Pro. Proc Natl Acad Sci 94, 7176.

Xu W, Chung DW, Davie EW (1996) The assembly of human fibrinogen. The role of the amino-terminal and coiled-coil regions of the three chains in the formation of the alphagamma and betagamma heterodimers and alphabetagamma half-molecules. J Biol Chem 271, 27948.

Hu CH, Harris JE, Davie EW, Chung DW (1995) Characterization of the 5'-flanking region of the gene for the alpha chain of human fibrinogen. J Biol Chem 270, 28342.

Davie EW (1995) Biochemical and molecular aspects of the coagulation cascade. Thromb Haemost 74, 1.

McMullen, B.A., Fujikawa, K., Davie, E.W., Hedner, U., Ezban, M. (1995). Locations of disulfide bonds and free cysteines in the heavy and light chains of recombinant human factor VIII (antihemophilic factor A). Protein Science 4, 740.