Grant: Project Grant

Cancers are caused by mutations and genetic alterations. Conventional origins of mutations from chemicals in the environment or inherited mutations are known, but we have just begun to understand that some mutations that contribute to cancer originate from within our own cells. There are enzymes that exist in our cells that can alter the DNA sequence. Usually these enzymes act for our benefit and use their activity to alter the DNA sequence of viruses to make the viral DNA nonfunctional. However, sometimes when the levels of these enzymes are not kept in check, they can become too high and they can alter the DNA sequence of the human cell. If these mutations occur in genes that contribute to cellular replication, they can induce the formation or propagate maintenance of a cancer cell. This research is focused on the internal origins of these mutations caused by a specific family of enzymes, called the APOBEC3 enzymes. If we can identify how their activity becomes unregulated we can design inhibitors to limit their function to slow cancer progression or use their unregulated activity as an early risk factor for cancer development.