Date of Award

Spring 2025

Project Type

Thesis

Program or Major

Genetics

Degree Name

Master of Science

First Advisor

Jingwei JC Cheng

Second Advisor

Sarah SW Walker

Third Advisor

Xuanmao XC Chen

Abstract

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer with a 30% mortality rate. In the United States, 80% of MCC cases are linked to the integration of Merkel cell polyomavirus (MCPyV), while the remaining cases are associated with excessive ultraviolet (UV) exposure, leading to UV-induced DNA damage. The therapeutic targets for MCC remain largely unknown. Elevated expression of Protein Arginine Methyltransferase-5 (PRMT5) has been observed in various cancers. My research aims to investigate how arginine methylation impacts the regulatory mechanisms of RNA-binding proteins and histone residues during neuroendocrine transdifferentiation in MCC. Recent studies suggest that low doses of PRMT5 inhibitors reduce cell viability in established MCC cell lines. As such, further investigation into the effects of PRMT5 inhibitors in MCC is crucial for developing effective combinatorial or dose-limiting therapies, an area that remains underexplored. This thesis will focus on PRMT5-mediated epigenetic modifications of RNA-binding proteins in Chapter 2 and the crosstalk between histone marks mediated by PRMT5 in Merkel cells in Chapter 3. Deepening our understanding of the biochemical roles of PRMT5-targeting drugs in MCC will contribute to the development of effective therapies for the disease.

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