Author Type

Undergraduate Student

Date of Award

Spring 4-30-2022

Document Type

Thesis

Publication Status

Version of Record

Submission Date

June 2026

College Granting Degree

Harriet L. Wilkes Honors College

Thesis/Dissertation Advisor [Chair]

Catherine Trivigno

Abstract

This project investigated the nuclear receptor LRH-1, which is primarily present in endodermal tissues. It affects several pathways such as lipid synthesis, glucose homeostasis, and embryonic development. However, LRH-1 is also often implicated in several cancers. In many types, tumorigenesis occurs due to LRH-1’s upregulation of the WNT/beta-catenin pathway, which promotes cell cycle progression. LRH-1 also promotes cancer proliferation by downregulating the cell cycle inhibitor p21. Targeting LRH-1 thus shows promise for treatment of the cancers it promotes. The small molecule SR1848 is an inhibitor of LRH-1 target gene expression, but it does not directly interact with LRH-1. This project aimed to identify the protein that SR1848 binds to using pulldown assays and LC-MS/MS. The four proteins GLUD1, CP, MDH2, and PPIB were identified as most likely to be the target, and validation experiments will be performed in the future to confirm whether one of them is the correct protein.

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