Identifying the regulatory targets of common endometrial cancer risk variants

Can be adapted in scope for Honours or PhD student.

BACKGROUND

We and our international Endometrial Cancer Association Consortium collaborators have identified common genetic variation at 16 genomic regions that associates 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, we have conducted global (HiChIP) analyses of DNA looping to identify physical interactions between genes and regulatory elements at endometrial cancer risk regions in endometrial cancer cell lines. These experiments constitute an essential step for the translation of genetic findings into advances in our knowledge of endometrial cancer biology and the identification of potential targets for therapy.

AIM

To identify high confidence gene regulatory targets of endometrial cancer risk variants using DNA looping analyses and other functional genomic datasets.

APPROACH

Depending on the applicant’s expertise, this project could have either a wet-lab and/or a bioinformatics focus. We already have a wealth of endometrial cell DNA looping data that can be coupled with complementary datasets (gene expression, histone modification and transcription factor ChIP-seq) for bioinformatic analyses to prioritise regulatory target genes. To extend our findings from DNA looping analysis of endometrial cell lines, we are also interested in performing analysis of human endometrial organoids from normal, hyperplastic and tumoural endometrium. These organoids should provide experimental systems that will better recapitulate the morphological and genomic features of human tissue.

OUTCOME

Through the identification of high confidence gene targets at endometrial cancer risk regions, we will gain a deeper understanding of endometrial cancer aetiology and identify potential targets for endometrial cancer therapy.