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Faculty Research Advisor
Merkel cell carcinoma is a rare but highly aggressive disease involving formation of potentially malignant tumors within the epidermis. Merkel cell carcinoma (MCC) disease states occur either from excessive UV exposure, or due to the presence of the Merkel cell polymomavirus (MCPyV). Although both underlying causes predict a similar prognosis, the various disease states differ in notable ways. MCC tumors that are UV-induced typically involve a high number of guanine to cytosine polymorphisms. Virus positive MCC tumors do not exhibit a significant number of G to C mutations, but rather contain integrated copies of viral DNA that encode for small T antigen and a truncated form of the large T antigen.
The EP400 histone acetyltransferase complex, comprised of at least 15 protein subunits, is involved in a variety of enzymatic activities including: chromatin remodeling, DNA helicase activity, and interactions with transcriptional factors. In MCC tumors that contain the MCPyV virus, the small T antigen plays a role in recruiting proteins to the EP400 complex and increasing oncogenicity. BRD8 and TRRAP are two of the subunits that comprise the EP400 complex. These proteins are therapeutic targets that provide opportunities to further investigate the nature of protein recruitment, interaction, and cellular transformation within the EP400 complex. Technologies such as CRISPR and RNA interference allow for disruption of these proteins at either the DNA or RNA level. These investigations illuminate the role played by EP400 and its subunits in the pathogenicity of Merkel cell carcinoma.
Fletcher, Robert; Veronneau, Katherine; and Paine, Marissa, "Investigating the Roles of BRD8 and TRRAP Proteins in Merkel Cell Carcinoma Oncogenicity" (2023). Undergraduate Research Conference (URC) Student Presentations. 576.