The Pursell Lab is interested in understanding how mutations are made, how they contribute to genome instability, and how they help facilitate tumor development. Our main focus involves studying DNA polymerases involved in DNA replication and DNA repair. Mutations in these DNA polymerases have been shown to contribute to human tumors, particularly in the colon and endometrium. We have shown that these DNA polymerase mutations make thousands of mutations and contribute to tumor development in a mouse model. We are currently working to understand several phenomena, including: how these mutations occur in unique sequence contexts, why certain tumor suppressor genes are enriched for mutagenesis, and how development of these tumors is accelerated or restrained. To do this we use genetically engineered cell lines (via CRISPR-mediated gene targeting), mouse models, whole exome/genome sequencing, mutation signature analyses, and in vitro biochemistry. We also collaborate with clinician-scientists to help understand the clinical significance of this polymerase-mediated mutagenesis.