White group | Developmental programmes in cancer
Dr RICHARD WHITE
Developmental programmes can be co-opted to drive cancer progression. Embryos are born with a set of genetic blueprints encoded in their DNA, yet during development, cells diversify to take on new fates above and beyond their genomes. This diversification is enacted in part by transcriptional/epigenetic programmes as well as cell-cell interactions. Similarly, tumour cells use many of these same developmental programmes but do so in the face of a highly disordered genome. Understanding how the cancer genome interacts with these developmental programmes is central to determining which cells are capable of tumour initiation and how they metastasize.
To address these questions, we primarily use the zebrafish as a model. An advantage of the zebrafish is that they are easy to genetically manipulate and image. Tumours develop in an intact microenvironment, allowing us to study the cell-cell interactions that are key to tumour progression. This is particularly enhanced in our transparent casper strain. We additionally use human pluripotent stem cell models of cancer to complement what can be done in vivo in the fish. Using state-of-the-art genetic engineering and imaging, we aim to dissect the mechanisms that allow a normal cell to become cancerous in the first place, and study how cell-cell interactions allow them to take on new properties.