Date of Award

Fall 2024

Project Type

Thesis

Program or Major

Biochemistry

Degree Name

Master of Science

First Advisor

Jingwei Cheng

Second Advisor

Sarah Walker

Third Advisor

Krisztina Varga

Abstract

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine skin cancer. In the United States about 80% of MCC cases are caused by MCPyV, which is the only human polyomavirus that has been directly correlated to human cancer. However, there is not a significant amount of information about pathways that are important in MCC. Here we show that MCC cells are reliant on the ATR-CHK1-WEE1 axis for proliferation and to maintain their oncogenic phenotype. We have found several inhibitors that work to reduce cell viability in MCC cells. Synergistic combinations of these inhibitors and chemotherapeutic agents have also been found. Additionally, the role of R-loops in the ATR-CHK1-WEE1 axis has been investigated. Our results demonstrate that the ATR-CHK1-WEE1 pathway is essential to MCC proliferation. We anticipate that this research can allow for a deeper dive into the intricacies of the ATR-CHK1-WEE1 pathway in MCC and can be the foundation for further pathway research within MCC.

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