Cancer cells can continually acquire new phenotypes such as therapeutic resistance that drive disease progression and lead to poor prognosis. How cells initiate and evolve resistance to many commonly used therapeutic agents is poorly understood, preventing the development of new more effective therapeutic strategies. The goal of this Ph.D. project is to develop novel approaches in both budding yeast and human cell culture model systems to uncover how cancer-associated cell phenotypes such as therapeutic resistance are controlled at the genetic level, ultimately to understand their molecular mechanisms and identify potential new therapeutic targets. This project offers an excellent opportunity to work with two different model systems, acquire bioinformatics skills, and develop and use state-of-the-art techniques in quantitative genetics, genomics, CRISPR/Cas9 genome editing and molecular biology. This project will make significant advances in our understanding of how cancer-associated cell phenotypes develop, and will ultimately shed light on how cancers arise and evolve.