Clinical ProfessorAssociate Director, Centre for Blood Research
The general expertise in our laboratory is the function of blood proteins and there novel application. By combining biochemistry and molecular engineering, we have discovered new functions of several proteins with possible therapeutic or diagnostic applications to heart disease and virus infection. Our long-range goal is to understand how these findings may impact on other blood protein functions and thereby contribute to optimizing the value derived from blood constituents and their substitutes.
Communication Between Clot-Forming and Clot-Dissolving Proteins
Clot generation (coagulation) and subsequent clearance (fibrinolysis) are fundamental biological processes. A high degree of communication between these opposing pathways is necessary to ensure that clots form and dissolve sequentially, and only when needed. The biological effector of coagulation, thrombin, is activated by an enzyme complex consisting of the protease factor Xa (FXa) and its cofactor Va (FVa). In recent work, Dr. Pryzdial’s group identified a previously unknown mechanism of communication between these clotting factors and the fibrinolysis pathway. The data revealed that FXa and FVa accelerate the clot-buster, tissue plasminogen activator (tPA), which is used as an important therapeutic. These studies suggest that the current fibrinolysis dogma must be revised to include auxiliary tPA cofactors, such as FXa and FVa, in the vicinity of the clot to further understand vascular health and pathology
Blood Proteins Exploited by Viruses
For decades many viruses have been linked to heart disease. To understand the molecular basis of the clinical correlation, Dr. Pryzdial’s group found that at least herpes simplex virus type 1 and type 2, and cytomegalovirus can directly assemble clotting protein complexes on their surfaces to generate thrombin. This bypasses the normally strict regulation of coagulation imposed by cells. Virus initiated clot formation not only contributes to heart disease, but enhances the susceptibility of host cell infection through protease activated receptors and possibly annexins. Dr. Pryzdial and his lab members are further dissecting the specific host- and virus-derived proteins on the virus surface that trigger coagulation and their role in virus propagation.
Ph.D., University of Toronto, Canada, 1987
B.Sc. (Biology, Chemistry, Biochemistry) University of Toronto, Canada, 1981
- Vanden Hoek, A.L., Talbot, K., Carter, I.S.R., Vickars, L., Carter, C.J., Jackson, S.C., MacGillivray, R.T.A and Pryzdial, E.L.G. (2012) Coagulation Factor X Arg386 specifically affects activation by the intrinsic pathway: A novel patient mutation. Journal of Thrombosis and Haemostasis Oct 5 doi: 10.111/jth.12021.
- Sutherland, M.R., Ruf, W. and Pryzdial, E.L.G. (2012) Tissue factor and glycoprotein C on herpes simplex virus type 1 are protease-activated receptor 2 cofactors that enhance infecton. Blood 119:3638-3645.
- Krisinger M, Goebeler V, Lu Z, Meixner SC, Myles T, Pryzdial ELG, Conway EM. Revising the terminal complement pathway: Thrombin generates previously unidentified C5 products which augment lytic activity. Blood 2012. 120(8):1717-25.
- Gershom. E.S., Vanden Hoek, A.L., Sutherland, M.R. and Pryzdial, E.L.G. (2012) Herpesviruses enhance fibrin clot lysis. Thrombosis and Haemostasis 107:760-768.
- Carter, S.R., Vanden Hoek, A.L., Pryzdial, E.L.G. and MacGillivray, R.T.M. (2011) Thrombin A-Chain: activation remnant or allosteric effector? Thrombosis doi:10.1155/2010/416167.
- Martinez-Gutierrez, F., Thi ,E.P., Silverman, J.M., de Oliveira, C., Svensson, S., Vanden Hoek, A., Sanchez,E.M., Reiner, N.E., Gaynor,E., Conway, E.M., Pryzdial, E.L.G., Orrantia, E., Ruiz, F., Av-Gay, Y., Bach, Y. (2012) Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles. Nanoparticles 8:328-336.
- Talbot, K., Song, J., Hewitt, J., Serrano, K., Ho, M., MacGillivray, R.T.A., Carter, C.J. and Pryzdial, E.L.G. (2010) A novel compensating mechanism for homozygous coagulation factor V deficiency suggested by enhanced activated partial thromboplastin time after reconstitution with normal factor V . British Journal of Haematology, 151:198-200.
- Gershom, E.S., Sutherland, M.R. and Pryzdial, E.L.G. (2010) Herpes simplex virus initiates the contactphase and intrnsic pathway of coagulation., Journal of Thrombosis and Haemostasis, 8:1037-104.
- Talbot, K., Meixner, S.C. and Pryzdial, E.L.G. (2010) Enhanced fibrinolysis by proteolysed coagulation factor Xa. Biochimica et Biophysica Acta 1804:723-730.
- Song, J., Talbot, K., Hewitt, J., MacGillivray, R.T.A. and Pryzdial, E.L.G. (2009) Differential contributions of Glu96, Asp102 and Asp111 to coagulation factor Va metal ion binding and subunit stability. Biochemical Journal 422:257-264.