Christopher Bresette

BME PhD Defense Presentation

Date: 2023-05-04
Time: 1:00pm - 3:00pm
Location / Meeting Link: EBB 3029 / https://teams.microsoft.com/l/meetup-join/19%3ameeting_ZTY3OTJjOGUtMDQ0ZS00NDkzLWFiN2YtYjBiZmEzZDhlYTRj%40thread.v2/0?context=%7b%22Tid%22%3a%22482198bb-ae7b-4b25-8b7a-6d7f32faa083%22%2c%22Oid%22%3a%22cce098bc-af7a-45af-b93a-2c40afb4a620%22%7d

Committee Members:
David Ku, MD, PhD (Advisor, ME); Ross Ethier, PhD (BME); Wilbur Lam, MD, PhD (BME); Michael McDaniel, MD (Division of Cardiology, Emory University School of Medicine); Cheng Zhu, PhD (BME)


Title: Measurement and Prevention of Occlusive Arterial Thrombosis

Abstract:
Arterial thrombosis is the process of forming a blood clot in an artery and is a leading cause of ischemic events such as heart attacks and strokes. Ischemic events account for 20% of all deaths in the United States. To reduce the mortality from ischemic events, we need better methods of predicting when arterial thrombi will form, new drugs that can prevent arterial thrombosis without increasing the risk of bleeding, and a better understanding of how large occlusive clots are structured and formed. This work has three aims, focused to improving the prediction and prevention of arterial thrombosis as well as contribute to our understanding of the basic science of how clots form large-scale architecture. In the first aim, a novel point-of-care device, the Thrombocheck, was developed. The Thrombocheck allows for measurements of thrombus formation to be taken in a clinical setting and is sensitive to anti-platelet treatment. In aim 2 we demonstrate that N-acetylcysteine (NAC), an existing drug used for treating acetaminophen overdose, can be repurposed as an anti-thrombotic medication. In a microfluidic with human blood and in an in vivo murine model, high doses of NAC completely prevent thrombus formation without increasing the risk of bleeding. Aim 3 described and quantified the complex structures formed in large clots. Using an agent-based model of arterial thrombosis, which treats platelets as autonomous agents, we demonstrated how the formation of large clot-level structure is an emergent property of simple platelet behaviors.