Blood Clotting and the Isolation of Factor V: the Work of Charles T. Esmon

Abstract

The Subunit Structure of Thrombin-activated Factor V. Isolation of Activated Factor V, Separation of Subunits, and Reconstitution of Biological Activity(Esmon, C. T. (1979) J. Biol. Chem. 254, 964–973) Charles Thomas Esmon was born in Centralia, Illinois in 1947. He received his B.S. in chemistry from the University of Illinois in 1969 and his Ph.D. in biochemistry from Washington University in St. Louis in 1973.​1973. Figure 1 Charles T. Esmon From 1974 to 1976, Esmon was a postdoctoral fellow with John W. Suttie at the University of Wisconsin, Madison. During this time he studied vitamin K and blood coagulation, and the pair published several papers on the subject in the Journal of Biological Chemistry (JBC), including Suttie's JBC 1976 Classic article (1). In 1976, Esmon became Assistant Professor in Pathology at the University of Oklahoma Health Sciences Center in Oklahoma City. He continued to study coagulation, focusing on Factor V, a glycoprotein that is proteolytically activated and is critical for blood clotting. At that time, little was known about the protein, in part due to the fact that it was hard to obtain reproducible and stable preparations of the factor in its activated and inactivated state. Most attempts at purification produced multiple structural forms with molecular weights ranging from 1.2 million to 38,000. In the Classic reprinted here, Esmon describes a method for isolating a high molecular weight form of Factor V, which could be cleaved by thrombin to form both an activation intermediate and a stable, fully activated Factor V. Esmon was able to dissociate the intermediate and the activated Factor V with chelating agents. From these results, he proposed a scheme for the activation of Factor V in which the protein is cleaved by thrombin into two chains that are held together by noncovalent interaction. Esmon remained at the University of Oklahoma and continued to study the mechanisms that control blood clotting and the links between clotting and inflammation. He has published more than 80 papers on the subject in the JBC. Currently, he holds the Lloyd Noble Chair in Cardiovascular Research and is Head of the Cardiovascular Biology Research Program at the Oklahoma Medical Research Foundation (OMRF). He is also a Howard Hughes Medical Institute Investigator and an Adjunct Professor of Pathology and Biochemistry at the University of Oklahoma Health Sciences Center. Esmon has received many awards and honors for his contributions to science. These include the Distinguished Investigator Award from the International Society of Thrombosis and Haemostasis (1983), the Merrick Award for Outstanding Research, OMRF (1983), the E. Donnall Thomas Prize from the American Society of Hematology (1995), the Edward L. and Thelma Gaylord Prize for Scientific Achievement, OMRF (2001), and election to the National Academy of Sciences (2002). He also served on the editorial board of the Journal of Biological Chemistry.