OHSU

Thrombosis and Hemostasis

thrombus formation

The objective of our research is to understand the mechanisms leading to thrombosis and select severe and prevalent ischemic and degenerative neurovascular and cardiovascular diseases and to develop more effective new drug therapies.

In particular, we are interested in understanding the interplay between the extracellular matrix, cell biology, and fluid mechanics in the cardiovascular system. The research into the balance between hydrodynamic shear forces and chemical adhesive interactions has great relevance to underlying processes of cancer, cardiovascular disease, and inflammation.

We investigate key hemostatic mechanisms, blood component interactions with natural and synthetic surfaces and the effects of blood-flow phenomena. For example, we are studying the role of contact activation in acute intraluminal thrombus propagation using ex vivo and animal disease models. If the functionality of the contact system enzyme complex is relevant to the pathogenesis of thrombosis but has limited role in hemostasis, a contact system inhibitor could become a safe antithrombotic agent. We also study the potential role of protein C in hemostasis. We are characterizing the effects of endogenous protein C activation on acute arterial thrombogenesis and hemostasis using rationally engineered recombinant enzymes. A pharmacologically viable protein C activator could help utilize the body's own antithrombotic and anti-inflammatory system similar to the way streptokinase and tPA became useful fibrinolysis activators. Moreover, we aim to identify thrombogenic and inflammatory triggers, including those that are associated with metastatic cancer, infections, and injuries, so that we can identify novel molecular targets for therapeutic interventions.

Faculty
Andras Gruber
Stephen Hanson
Monica Hinds
Owen McCarty
Sandra Rugonyi