“The two magic words of hemostasis: amplification and regulation”

Professor Joost Meijers

Professor Joost Meijers

Professor Joost Meijers is manager of the Plasma Proteins department of the Research Division of Sanquin. He started his career at Utrecht University, became professor at the AMC Amsterdam and joined Sanquin in 2014. Besides doing research he committed himself to teaching and was involved in numerous committees in the field of hemostasis and fibrinolysis. He is currently chairman of the ISTH SSC Subcommittee on Factor XI and the Contact System, Secretary/Treasurer of the International Society on Fibrinolysis and Proteolysis, and is member of the Executive Board of the Dutch Thrombosis Foundation.

You moved to Sanquin in 2014. How do you like it here?
The number of scientists working on hemostasis in the Netherlands is rather small. At Sanquin I am part of an entire team of scientists all dedicated to this field of research. It feels like coming home. Besides, there is a great deal of biochemical expertise throughout the institute. My research group runs like a well-oiled machine. People all work from an inner motivation. That means that although I’m the manager I can still spend most of my time on research.

Why are so many factors and proteins involved in the homeostasis process?
This can be explained by two magic words: amplification and regulation. When we bleed the body should respond with a powerful reaction to stop the bleeding. Therefore we need amplification. This is necessary for swift coagulation at the site of the injury. But this process could derail tremendously. All kinds of regulatory proteins take care of keeping the coagulation process in control. Nevertheless, in the Netherland 400,000 people need anticoagulants to prevent thrombosis. These medications are also prescribed to hospitalized patients. Doctors of nearly all medical disciplines need to deal with coagulation abnormalities. Thrombosis can be seen as too much coagulation at the wrong place at the wrong time.

What is the importance of the contact pathway of coagulation?
The proteins of the contact system, factor XI, factor XII, prekallikrein and high-molecular weight kininogen, were discovered in the 1950s and 1960s. Blood drawn from patients with a factor XI deficiency shows a prolonged clotting time. Obviously, at the time it was thought that the contact system was necessary for proper coagulation. But curiously, those patients hardly have any bleeding problems. The coagulation delay is foremost an in vitro phenomenon. Now we think that the contact system contributes to thrombosis. For instance knock-out mice deficient in one of the contact proteins are protected against thrombosis.

What will be the anticoagulant of the future?
Current medicines like heparin, vitamin K antagonists or direct oral anticoagulants all have one important side effect: bleeding. With my team I focus on development of inhibitors of factor XI. That could be a safe alternative for the currently available drugs. You could think of monoclonal antibodies or small molecules. To develop inhibitors in our lab we want to know everything about factor XI. How does it work? How does it react with factor XII and thrombin? When we understand which part of the molecule is important for its function we can better attack the protein. But we would also like to develop an improved factor XI protein, one that stimulates coagulation. That could help patients with bleeding disorders like hemophilia.

What would you like to achieve at Sanquin?
Recently the Molecular Cell Biology department, with their expertise on blood vessels, was integrated in our department. I want to combine both research fields. It is the blood vessel wall where bleeding, coagulation and thrombosis all start. Endothelial cells play an important role in hemostasis. We can learn a lot from each other and together we can do high quality research. I hope I can obtain a European grant for continuing fundamental research on factor XI, in the end hopefully leading to development of pro- and anticoagulant medication. We already work together with a Dutch company to identify small molecules that stimulate coagulation and may be useful in patients with bleeding disorders.

Finally, what goes through your mind when you bleed?
When I accidentally cut my finger I can only see the beauty in the blood. I think of the interplay between systems that cause my blood to clot. That is, of course, before putting a sticking plaster on my finger.

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