FOXA1 mutations in Lobular Breast Cancer: Reprogramming Responses to Tamoxifen

Tumours of the breast are often hormone-dependent, meaning their growth is driven by steroid hormones such as estrogen. This hormone acts upon the estrogen receptor (ER), which together with other transcription factors such as FOXA1 drives tumour growth. While some patients respond well to hormone therapies such as Tamoxifen, others show a poor response. It is now clear there are different molecular subtypes of breast cancer that respond differently to hormone therapy. However, mechanisms of resistance are incompletely understood. The aim of this project is to investigate the mechanisms underlying the poor response to hormone therapies shown by patients with invasive lobular breast cancer (ILC), a subtype accounting for 10-15% of breast tumours that show a relatively high incidence of FOXA1 mutations.
The project will provide training in state of the art molecular techniques including identification of ER and FOXA1 regulated genes in ILC tumours and cell lines, and the effect of FOXA1 mutations on the assembly of complexes on target genes. The student will have opportunities to learn techniques such as CRISPR CAS9 genome editing of cell lines, RNA Seq, ChIP-Seq and/or RIME.

Environment & Supervision
The project will be jointly supervised by Prof. Heery (Pharmacy- Gene Regulation) and Dr Simon Johnston (Clinical Oncology).The majority of the project will be carried out within the Gene Regulation & RNA Biology Group within the Division of Biomolecular Sciences & Medicinal Chemistry, School of Pharmacy. The School of Pharmacy provides a vibrant cross-disciplinary research environment, with excellent support and training facilities for PG students.