Thrombosis Systems Bioengineering
We are interested in the development and clinical translation of diagnostic tools for blood clotting disorders associated with cardiovascular disease, diabetes, chronic liver cirrhosis, sepsis, and cancer. We are applying microfluidic systems integrated with optical and acoustic force probes to define fundamental regulatory mechanisms underlying hemostasis and thrombosis. We are also developing computational approaches to identifying how the immune system and the coagulation system contribute to the progression of multifactorial diseases such as diabetes and atherosclerosis.
Blood Coagulation Mechanics and Platelet Function
Our core interest is in the mechanobiology of the blood platelet during thrombosis, the pathological process of blood clotting that can lead to stroke, myocardial infarction, or deep vein thrombosis. Platelets are important regulators of blood clot formation through two mechanisms. One, platelets catalyze thrombin generation to form the fibrin polymer network that creates the blood clot structure. Second, platelets play a key role in fibrin bundling through their IIBIIIA integrins that amplify overall clot strength. To understand how platelets regulate blood coagulation we've developed a novel technology based on acoustic radiation force called sonorheometry that quantifies blood clot viscoelastic properties. With this tool we can track the evolution of the clot's fibrin protein network and platelet modulation of its stiffness via integrin interactions in real-time. Platelet function is therefore assessed in its natural 3-D environment, the blood clot, allowing interrogation of relevant signaling pathways that ultimately regulate blood clot mechanical properties. Platelet regulation of blood clot mechanical properties is critical for successful hemostasis and the avoidance of life-threatening thrombosis.
Sonorheometry assessment of blood clot viscoelasticity also permits clinically relevant assessments of the ability of a patient's platelets to stem bleeding. Real-time sonorheometry measures of the effectiveness of a patient's coagulation system can potentially be used to diagnose blood clotting disorders and guide treatment during complex cardiac and neurological surgeries.