Christopher Bresette
BMED PhD Thesis Proposal  

Date: 08/10/2021  
Time: 2-3 PM  
Location: Bluejeans (https://bluejeans.com/402212410/8560)  

Faculty Advisor:  
Dr. David Ku  

Committee Members:   
Dr. Ross Ethier (GT)  
Dr. Wilbur Lam (GT)
Dr. Michael McDaniel (Emory Cardiology)  
Dr. Cheng Zhu (GT)  

Title: Measurement and Prevention of Occlusive Arterial Thrombosis

Abstract: Arterial thrombosis is a leading cause of heart attacks and strokes. Previously developed assays fail to include the critical variables required for arterial thrombosis and are unable to aid clinicians in predicting future events or making patient-specific changes in treatment for secondary prevention. There remains a need for a point-of-care (POC) test that accurately models arterial thrombosis. Additionally, it has been hypothesized that targeting the shear-sensitive von Willebrand Factor (vWF) could allow for prevention of arterial thrombosis without adverse effects on coagulation and low-shear hemostasis. N-acetyl-cysteine (NAC) is an existing drug that cleaves long vWF multimers into smaller, less active multimers. The overall goals of this proposal is to create a POC for arterial thrombosis and investigate the use of NAC for prevention of high-shear thrombosis. Creating a low variability assay based on our model of arterial thrombosis will provide a unique result from existing platelet function assays and accurately reflect the effects of anti-thrombotic agents on a patient’s thrombogenicity. I also aim to demonstrate that NAC can be used in a population with normal vWF multimers to reduce arterial thrombosis. Finally, I predict that the primary mechanism of action for NAC-mediated prevention of arterial thrombosis is through modification of the A1 domain, not the well-studied reduction in vWF length.