The ASPIRE Path in Molecular Medicine

My proposed thesis project aims to utilize an in vivo CRISPR screens of cell-free DNA (cfDNA) to identify specific cancer mutations of circulating tumors. Circulating tumor DNA (ctDNA) and cfDNA are widely used for diagnostic tests in various fields of medicine including oncology. The ability to detect tumor-specific mutations in cfDNA shed from precancerous or metastatic lesions would be invaluable for precision oncology. Current liquid biopsy tests for ctDNA or cfDNA have limited sensitivity and poor negative predictive power. Currently, several clinical trials are using low-sensitivity ctDNA tests as their measurement of drug success. The goal of my thesis project is to successfully detect and identify specific tumor mutations from cfDNA in the bloodstream of a mammal. To accomplish this we hope to utilize a drug cocktail that is suspected to increase the amount of cfDNA released by inducing apoptosis at a higher rate and inhibit nucleases from degrading released cfDNA. A long term goal of this thesis project is to improve both the sensitivity and specificity of current liquid biopsy tests.