680611 event 1739989162 1739989207 Jessica Lin
BME PhD Defense Presentation

Date: 2025-03-05
Time: 3:00 PM-5:00 PM
Location / Meeting Link: EBG 4029 / Zoom link: https://emory.zoom.us/j/96805006414

Committee Members:
Wilbur Lam, MD/PhD (Advisor); Anton Bryskin, PhD; MG Finn, PhD; Erik Dreaden, PhD; Karmella A. Haynes, PhD


Title: Engineered bacterial surface display of fibrinolytic protein for the treatment of thrombotic disease

Abstract:
Thrombosis is at the root of several leading causes of death globally, including myocardial infarction, ischemic stroke, and venous thromboembolism. Currently, acute thrombotic disease is often treated with thrombolytic drugs such as tissue plasminogen activator, which can quickly digest blood clots but has adverse bleeding effects that prevent prophylactic use, a short window of use, and several contraindications that limit use in many patients. Bacteria have long been explored for treatment of cancer and metabolic diseases, due to their ability to respond to external signals and target specific microenvironments. The range of bacterial strains and synthetic biology tools that have been developed make bacteria a flexible chassis for delivery of therapeutic proteins. Streptokinase is a fibrinolytic protein that has long been used for clinical treatment of myocardial infarction, making it an ideal target for bacterial delivery. In this thesis, I develop a bacterial surface display system to express the fibrinolytic protein streptokinase on the surface of E. coli. I develop a microfluidic model of thrombosis to characterize the dynamics of clot digestion and demonstrate the longer activity window and localized fibrin digestion of bacteria surface displayed streptokinase compared to free streptokinase. Finally, I explore different methods of regulating bacterial growth and protein expression using in-situ induction and antibiotic treatment, and propose a novel paradigm for thrombolytic therapy.

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