Mettine Bos, Division of Thrombosis and Hemostasis, Leiden University Medical Center,
Selective Tuning of Blood Coagulation Proteases to Treat Bleeding
Life-threatening bleeding events are substantial complications for patients witha compromised blood coagulation response. The inability to clot efficiently can result from treatment with anticoagulants or is caused by a congenital or acquired bleeding disorder. Dr. Bos aims to engineer innovative variants of blood coagulation proteases to improve treatment of bleeding. Her research explores evolutionary adaptations in snake venom coagulation factors to identify modifications that could enhance the functionality of blood coagulation proteases.This has led to the development of factor X variants that maintain procoagulant activity butare resistant to direct Xa inhibitors, creating potential reversal agents for anticoagulant drugs in emergencies, such as life-threatening bleeding. One such variant is advancing inclinical development. Another area of her research involves engineering factor IX variants that operate independently of factor VIII, presenting a promising treatment approach forhemophilia A. To support these efforts, Dr. Bos uses cutting-edge computational techniques,including AlphaFold and molecular dynamics simulations, for protein structure and interaction modeling. These tools, combined with biochemical characterization and preclinical validation,enable the precise tuning of serine proteases to produce prohemostatic agents, thereby addressing unmet needs in the treatment of bleeding.)
Developing a multiscale understanding of energy-utilizing polymers
Abstract: TBP