UCSF

Cell surface proteolysis plays a crucial role in regulating various biological and cellular processes, including but not limited to cell signaling, protein maturation, and extracellular matrix remodeling. Dysregulation of these proteolytic events is often a hallmark of numerous diseases. Understanding these changes in proteolysis may present opportunities for therapeutic intervention as neo-epitopes are created that may be preferentially displayed in diseased states. Under hypoxic conditions, Pancreatic Dunctal Adenocarcimoma (PDAC) experiences global changes to its cell surface proteolytic state. Additionally, it is important to understand the mechanism of action for protein-protein interactions in disease, particularly in the case of viral infection, as these interactions may be therapeutic targets for disruption. The following work describes the development of novel protein tools to understand how cell surface proteolysis changes when various oncogenes are overexpressed in breast cancer and how SARS-CoV-2 Spike protein interacts with the human ACE2 receptor. In Chapter 1, I describe the work done to develop a method utilizing subtiligase to study changes to the proteolytic landscape of MCF10A cells under the influence of KRAS G12V and Her2 overexpression. Chapter 2 describes the work done in studying the effect of hypoxia on cell surface proteolysis in Pancreatic Ductal Adenocarcinoma (PDAC). In Chapter 3, I describe the develop of various protein-Fc fusions to study the protein-protein interactions of Spike protein and ACE2.