I am interested in the genomic and molecular mechanisms underlying resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone-receptor positive (HR+) metastatic breast cancer. These agents have become the standard of care in this disease, but we have little insight into the mechanisms governing response or resistance in human patients. We have been utilizing next-generation sequencing (primarily whole exome) in collaboration with our colleagues at the Broad Institute to identify putative drivers in resistant tumor biopsies. Our work has led to the identification of multiple novel mediators of resistance, which we have been validating in the laboratory in vitro. It is our hope that these results will be readily translatable to the clinic, as many of these novel resistance mediators are actionable.