John A. Frank, PhD, Postdoctoral Fellow Yale University Area of Research: All Cancers Retroviruses, like HIV, have long been known to play a significant role in the emergence of human cancers. Retrotransposons are mobile genetic elements that are related to retroviruses and frequently expressed in various cancers. These elements can replicate within our cells and account for ~35% of the human genome. Their mobilization and expression have also been associated with human cancer emergence, evolution, and spread. Thus, it is critical to understand how expression of these elements is regulated. Retrotransposons contain regulatory sequences that coordinate their expression and replication. It is suspected that cellular antiviral factors may control their activity. APOBEC3A (A3A) is an antiviral factor that blocks retrovirus replication by mutating the retroviral DNA. Dr. Frank seeks to determine if and how A3A interferes with retrotransposon expression. His lab recently discovered that A3A can repress expression of the well-known human retrovirus, HIV. Using both experimental and computational approaches in human immune cells, he will now investigate whether A3A controls retrotransposon expression. This project will identify specific retrotransposons that are targeted by A3A and characterize whether these elements impact cell characteristics, like cell propagation or immunity. Further, this work will reveal a novel and biologically significant mechanism of retrotransposon control. Finally, the data and insights generated by the proposed work may inform future studies focused on APOBEC3 gene family contributions to genome function in human cancers as well as the development of immunotherapies that target retrotransposon proteins expressed in various cancers. Projects and Grants APOBEC3 proteins are potential repressors of retrotransposon transcription Yale University | All Cancers | 2021 | Akiko Iwasaki, PhD
