The double-edged sword of APOBEC3:Can we wield it to defeat cancer?”

Dr. Green is focused on the origins of cancer and the sources of DNA mutations that contribute to the initiation and progression of cancer. Her overall goal is to understand how mutations occur, in order to prevent cancer progression and to design new, targeted treatment approaches. Through cancer genome sequencing, the APOBEC3 family of proteins has been identified as a source of DNA mutation. The normal function of APOBEC3 proteins is to damage the DNA of viruses in order to limit virus infection as a part of our immune systems. However, prior work in Dr. Green’s lab has shown that when there are unusually high levels of APOBEC3 proteins in cells, they can also damage the cell’s own DNA, which causes mutations. The mutational pattern that appears to be caused by APOBEC3 proteins has been found in many human cancers including breast, bladder, ovarian, lung, and leukemia.

Additionally, too much APOBEC3 activity can result in widespread DNA damage causing cell death, which suggests that a targeted treatment that increases APOBEC3 activity could cause cancer cell death. On the other hand, limiting APOBEC3 could reduce mutations in cancer that result in disease progression. Dr. Green plans to focus on both aims: how APOBEC3 proteins can be used to kill cancer cells and how inhibiting APOBEC3 can limit cancer progression. By developing novel models and using new inhibitors and processes in collaboration with leaders in the field, Dr. Green hopes to shed light on how changes in the levels of this family of proteins might be leveraged against many types of cancer.