The ASPIRE Path in Molecular Medicine

My intended thesis project will identify changes in genome methylation associated with drug resistance in breast cancer. Genes of interest will be identified via a CRISPR screen utilizing an enzymatically dead Cas9 protein fused to a methyltransferase for targeted methylation of individual genes. Gene hits will be validated with methylome sequencing and individual manipulation in breast cancer cell lines. Further studies will determine the effects of methylation of validated genes on drug resistance in vivo. While this project is rooted in basic science, dissecting treatment resistance in breast cancer has high potential for clinical translation. I plan to integrate clinical data by leveraging genomic databases to determine whether epigenetic signatures of resistance discovered through my work are found in patients with therapy-resistant breast cancer. This aspect of my project alludes to the APMM’s goals by fusing basic and translational science to bring laboratory discoveries to human subjects. The APMM program will be instrumental for inspiring and guiding any translational aspects of my project to make it more applicable to a clinical setting. Having the knowledge to shape my work to be more patient-focused will elevate my project’s eventual findings to better serve those it is intended to benefit.