jhmorris@uiuc.edu
417 Medical Sciences Bldg
Office: (217) 265-4036
Fax: (217) 265-5290
Mail to:
University of Illinois College of Medicine
417 Medical Sciences Building, MC-714
506 S. Mathews
Urbana, IL 61801
James H Morrissey
Professor of Medical Biochemistry in the College of Medicine
Professor of Biochemistry
Director of the Cell and Molecular Biology Training Program
Education
B.S. M.S. 1975 University of California, Irvine
Ph.D. 1980 University of California, San Diego
Postdoc. 1981-1983 Oxford University, 1983-1984 The Scripps Research Institute
Regulation of protease cascades; blood clotting; protein-phospholipid interactions
A number of important biological processes, including apoptosis, the complement system and blood coagulation, are controlled by protease cascades. A key regulatory feature of such cascades is the modulation of protease function by highly specific protein cofactors, and interestingly, these cascades often can only take place on membrane surfaces. Although much is known about the general catalytic mechanism of serine proteases, far less is known about the roles of protein cofactors and membrane surfaces in regulating protease function. In our lab we are studying serine proteases in the blood clotting cascade with a goal of understanding the contributions of protein-protein and protein-phospholipid interactions to catalysis. Very recently, we have discovered that polyphosphate (a polymer of inorganic phosphate) potently modulates the blood clotting cascade. Polyphosphate, which is secreted from activated platelets and also accumulates in many microorganisms, is thus a natural modulator of blood coagulation and fibrinolysis. The mechanism by which it does this is not well understood.
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?
- How does polyphosphate modulate blood clotting and fibrinolysis?
- As a spinoff from these basic studies, we are working to develop:
- Improved hemostatic agents to treat surgical and traumatic bleeding
- Improved diagnostic tests for identifying persons at risk of thrombotic disease
Representative Publications
Shaw, A.W., Pureza, V.S., Sligar, S.G., and Morrissey, J.H. 2007. The local phospholipid environment modulates the activation of blood clotting. J. Biol. Chem., 282:6556–63. [Abstract]
Smith, S.A., Mutch, N.J., Baskar, D., Rohloff, P., Docampo, R., and Morrissey, J.H. 2006. Polyphosphate modulates blood coagulation and fibrinolysis. Proc. Natl. Acad. Sci. USA, 103:903–8. [Abstract]
Waters, E.K. and Morrissey, J.H. 2006. Restoring full biological activity to the isolated ectodomain of an integral membrane protein. Biochemistry, 45:3769–74. [Abstract]
Waters, E.K., Yegneswaran, S., and Morrissey, J.H. 2006. Raising the active site of factor VIIa above the membrane surface reduces its procoagulant activity but not factor VII autoactivation. J. Biol. Chem., 281:26062–8. [Abstract]