We and our Endometrial Cancer Association Consortium (ECAC) collaborators have identified common genetic variation at 20 genomic regions that associate with endometrial cancer risk. Although we have identified potentially causal risk variants, at most regions we do not know which genes these variants target. However, at two regions we have used DNA looping analyses to identify genes that interact with risk variants and, in follow-up experiments, shown that risk variants regulate gene activity. These experiments constitute an essential step for the translation of genetic findings into advances in our knowledge of endometrial cancer biology.
To identify the gene regulatory targets of endometrial cancer risk variants using DNA looping analyses and other experimental techniques.
DNA looping analyses can be identified using approaches such as HiChIP that can identify genomic regions that interact with the promoters of all active genes, while other techniques (e.g. 3C) can be used to analyse interactions with specific genes. We will use both approaches to identify genes that are targeted by endometrial cancer risk variants. We will also perform follow-up experiments using reporter gene assays to determine if risk variants affect gene activity.
The identification of the gene targets of risk variants will not only identify pathways that are involved in endometrial cancer development but also provide potential targets for the repurposing of existing drugs or the development of novel therapies.
- PhD project, may also be considered for an Honours project.