Collectively, bleeding and thrombosis are leading causes of death among the elderly (heart attacks and stroke) and the young (traumatic hemorrhage). My goal is to gain a deeper understanding of the underlying mechanisms of coagulation that tips the scale away from the much-needed hemostasis and towards the deleterious bleeding and thrombosis. If a “bad” blood clot can be understood, then the development of therapeutics to engineer stable blood clots becomes realistic and achievable. Our research combines medicine, engineering, computational and structural biology to make novel advancements in understanding bleeding and thrombosis.
kinetics, mechanics, and structure of contracting blood clots
Blood clot contraction, or the volume shrinkage of the clot, has been implicated to play a role in hemostasis and thrombosis. We use in vitro assays to examine how the cellular and molecular composition of the blood influences the process of contraction. The contraction process results in the redistribution of platelets and fibrin to the exterior of the clot and the compaction of red blood cells into the core of the clot. Current projects include investigating how these structural changes in contracting clots influence the mechanical properties of the clot.
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Pathophysiological importance of blood clot properties
We explore the mechanistic differences of clot contraction in healthy individuals and those with (pro)-thrombotic conditions by examining blood samples from patients with conditions such as ischemic stroke, sickle cell disease and deep vein thrombosis. These studies revealed that clot contraction is reduced in patients with these conditions when compared to healthy subjects. We show the extent of clot contraction influences the resolution of blood clots through a process called fibrinolysis, we are currently exploring the mechanism(s) underlying this altered resolution. In addition, we are examining the structure, mechanics, and contractility of blood in bleeding conditions.
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Rupture resistance of blood clots
Blood clots and thrombi must be able to resist breaking to prevent bleeding and embolization. Fibrin, a major components of the blood clot that provides much of the mechanical stability, must be able to resist hydrodynamic forces due to platelet contraction, blood flow, and muscle contractions. Ongoing studies explore the mechanism(s) of how fibrin resists rupture and understanding why blood clots fail in pathological settings. Fibrin is also a versatile biomaterial and these studies are paramount for the development of mechanically tunable fibrin-based biomaterials.
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