Ed Pryzdial

The general expertise in our laboratory is the function of blood proteins and their 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 substitute

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.

Virus-Induced Coagulopathy

Most (if not all) viruses that have a cell membrane sheathing, called an envelope, influence our clotting system. Mainly focusing on HIV, dengue virus and oral herpes virus, the Pryzdial team is seeking to find a common molecular basis to explain how these viruses trigger clotting and then design the first broad-spectrum antiviral agent to alleviate their respective pathologies.

Clot-Busting Enhancers

The favored clot-busting drug (rtPA) causes life-threatening bleeding far too often in patients with heart attacks, stroke, or deep vein thrombosis: approximately 6%. The Pryzdial Lab has discovered an overlooked mechanism that facilitates clot-busting without the need to administer rtPA, thus improving patient safety. Development of this new mode is underway using recombinant technology and preclinical animal models.