Honors Theses and Capstones

Date of Award

Winter 2024

Project Type

Senior Honors Thesis

College or School

COLSA

Department

Molecular, Cellular, and Biomedical Sciences

Program or Major

Biomedical Science: Medical Microbiology

Degree Name

Bachelor of Science

First Advisor

Sarah Walker

Abstract

Ovarian cancer is the most fatal female reproductive cancer, with most cases being diagnosed in late stages, after metastasis has become widespread. This can make ovarian cancer challenging to successfully treat, especially with its high rate of recurrence. The use of small molecule compounds to inhibit overexpressed transcription factors may provide an effective method for treatment. BCL6 is a transcription factor that is abnormally overexpressed in patients with recurring and late-stage ovarian cancer and has been implicated in proliferation and metastatic behavior. The identification of multiple potential inhibitors of BCL6 could improve chances for the further testing of these compounds, and eventually for use in ovarian cancer treatment. A former Walker lab member identified a novel compound, originally designed to inhibit an nRTK, as a possible BCL6 inhibitor. Additional testing of this compound, alongside a known BCL6 inhibitor, FX1, was performed to provide insight into the function of this new compound in BCL6 inhibition. This was achieved using RT-qPCR, western blot analysis, dual-luciferase assays, Cell TiterGlo viability assays, and mesothelial clearance assays. Additionally, DNA nanoswitches, a novel tool to assess transcription factor activity in real-time, were tested for possible use in mesothelial clearance. Based on initial testing, they show potential as a method of identifying real-time changes in transcription factor activity, as well as localization of this activity. Overall testing showed that the compound identified by a former lab member significantly decreases mesothelial clearance in ovarian cancer, and may be inhibiting BCL6 through a currently unclear mechanism.

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