Colorectal cancer is the fourth most common cancer in the United States. Rates of diagnoses have doubled in the past decade for adults under the age of 55. Radiation and chemotherapy treatments are often combined to treat rectal cancer. Up to 50% of rectal cancers resist initial therapy with chemotherapy and radiation, necessitating large operations for these patients. Our previous data in lung cancer cell lines implicates radiation-induced activation of enhancers, suggesting that in some tumor types, epigenetic reorganization may determine radioresistance. However, it is unknown if this phenomenon also occurs in colorectal cancer, hindering the development of radiosensitizing strategies for rectal cancers. To investigate this, we utilized RNA Sequencing (RNA-Seq) and Assay for Transposase- Accessible Chromatin Sequencing (ATAC-Seq) protocols and analyses in cells treated with various doses of radiation to assess whether consistent epigenetic reorganization was present or absent in colorectal cancer cell lines. Four established colorectal cancer cell lines, SW480, HCT116, RKO, and MDST8, were selected for this project. These colorectal cancer cell lines were chosen from a preliminary radiosensitivity assay identifying radiosensitive and radioresistant cell lines. They were given two courses of treatment. The first treatment group was irradiated with a singular 0Gy, 2Gy, and 5Gy treatment and harvested 5 days later. The second group was irradiated with 0Gy or 2Gy daily for 5 days, then harvested 5 days after the final radiation treatment. These radiation doses were chosen to closely match clinically relevant therapies. Each cell line and treatment combination were performed in triplicates, allowing for analyses of 60 samples. RNA-Seq was performed to analyze radiation-induced gene expression changes, while ATAC-Seq analyzed open chromatin regions in the cell line's genome. Preliminary results suggest that specific enhancers are activated post-radiation treatment in these cell lines, corresponding to specific gene expression changes, indicating potential resistance mechanisms to radiation treatments. The future direction for this research involves designing epigenome-targeting screens to identify radioresistant events. Ultimately, this project contributes to a greater understanding of how radiation-induced epigenetic reorganization may affect cancer progression and outcomes. Characterization of Mouse Models of Pain following Adoptive Transfer of SLE Serum

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