Latest News:
- 8/2025 Our cryo-EM structure of the membrane-bound tissue factor/factor VIIa complex with a
factor X mimetic is now published in Blood, revealing how the trimolecular complex that
triggers blood clotting in both normal hemostasis and many thrombotic diseases
assembles on a membrane surface. This structure now provides a clear mechanistic
explanation for more than 30 years’ worth of biochemical studies about tissue factor’s
substrate-binding “exosite.” It also reveals a novel, membrane-dependent allosteric
activation mechanism to explain the otherwise puzzling phenomenon of
encryption/decryption of cell-surface tissue factor. This study was a highly rewarding
collaboration between the labs of James Morrissey, Melanie Ohi, and Michael
Cianfrocco at the University of Michigan, and Emad Tajkhorshid’s group at the
University of Illinois.
- 2/2025 Our lab’s latest paper, “Membrane-bound model of the ternary complex between factor VIIa/tissue factor and factor X,” is featured on the cover of Blood Advances.
- 3/2024 NHLBI published a shout-out for our work collaborative work with the Kizhakkedathu lab on the neutralization of polyphosphate by MPI 8
- 1/2024 Congratulations to Josepha for receiving the Aminoff Endowment award from the UMich Biological Chemistry department
Click here to see more news from the Morrissey Lab
About the Lab
The research conducted in our laboratory focuses on understanding how cells regulate blood clotting in health and disease. The blood clotting system is activated when an enzyme (a specific plasma serine protease known as factor VIIa) binds to a particular integral membrane protein (known as tissue factor, or TF) on cell surfaces. The TF-VIIa-membrane complex triggers the blood clotting cascade by activating two plasma serine protease zymogens (factor IX and factor X) via limited proteolysis.
Thrombosis is the formation of unwanted blood clots inside arteries and veins, which represents the leading cause of disability and death in the world. Tissue factor is the protein that triggers thrombosis in many–possibly most–disease settings. For this reason, it is critically important to understand how the initiation of coagulation is controlled via tissue factor and factor VIIa.
Our studies are funded by research grants from the National Heart Lung and Blood Institute,the American Heart Association and other funding agencies.
We are currently focusing on the following research questions:
- How do the serine proteases of the blood clotting system assemble together with specific regulatory proteins on cell surfaces and other membrane surfaces?
- Why are membranes required for efficient proteolysis by these enzymes? What role do specific phospholipid types play in modulating the activity of blood clotting proteases?
- We recently discovered that inorganic polyphosphate secreted from activated platelets is a potent modulator of blood clotting and fibrinolysis. What’s the mechanism by which polyphosphate does this?
- As a spinoff from this basic research, we are also working to develop:
- Improved diagnostic tests for identifying persons at risk of thrombotic disease.
- Improved hemostatic agents to treat bleeding, including traumatic and surgical bleeding3