Identifying new ways to target cancers with DNA repair defects

• PhD
• Graduate Research Masters
• Honours

Cytidine deaminases from the APOBEC-family play a key role in defending cells against viruses. They do this by binding and editing the viral genome. Unfortunately, these enzymes also damage cellular DNA and they make a major contribution to the mutational landscape of cancers from the bladder, skin, breast and lung.

This project will develop new models of APOBEC driven cancers. We will investigate how APOBEC guides the development of cancer across different tissues. This element of the project will involve genomic and transcriptional profiling of cancers.

We are also searching for new ways to treat these cancers. We will use genetic screens and functional assays to find new ways to selectively kill cancer cells with high APOBEC activity.

Our research investigates why cancers develop and how they change in response to therapy. Our primary strengths are in cancer genetics and genomics, with an emphasis on DNA repair. We use genomic approaches to study the genetic and transcriptional landscape of cancer, then we model these alterations to determine precisely how they work.

This project builds on preliminary studies performed in our lab that have established a new way to activate APOBEC. The project should appeal to students who want to gain expertise in cancer biology, genomics and molecular biology.

These papers help illustrate the type of work that we do:

• Fang, Genome Medicine 2022 31;14(1):124
• Palles, American Journal of Human Genetics 2022 109(5):953
• Sanders, Blood 2018 132(14):1526