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Presentation Time: 4:00-4:20
Home University: UNC-Chapel Hill
Research Mentor: Samantha Pattenden, Chemical Biology and Medicinal Chemistry
Program: SMART
Research Title: Testing the effects of Corin on chromatin accessibility in Ewing sarcoma

Ewing Sarcoma is a pediatric bone cancer driven by a chromosomal translocation, which in some cases leads to the expression on an oncoprotein, EWS-FLI1. EWS-FLI1 drives the cancer cells by altering the transcription program and creating aberrantly accessible regions of chromatin. Histone deacetylase inhibitors (HDACi) reverse the Ewing-Specific chromatin accessibility pattern by suppressing transcription of the EWS-FLI1 protein, which in turn stops cancer cell proliferation. Lysine specific histone demethylase inhibition (LSD1i) reverses Ewing sarcoma-specific transcription programs. The overall goal of this project is to test a compound called Corin which is a dual inhibitor with HDACi and LSD1i warheads. We hypothesize that Corin may have a more potent effect on aberrant chromatin accessibility and gene expression than either LSD1i or HDACi alone in Ewing sarcoma cells. Initially, we optimized the cell parameters by plating the appropriate cell numbers per well of a 384-well plate, making sure cells remain viable after compound treatment. We then treated cells with Corin, LSD1, and HDAC for 24 or 48 hours, then the Assay for Transposase Accessible Chromatin (ATAC) was performed followed by the quantitative polymerase chain reaction (qPCR) to examine changes in chromatin accessibility. Currently, the use of Corin as a combination therapy to treat Ewing Sarcoma is a speculative approach. Although with succuss, this could one day be used as a treatment for Ewing Sarcoma.