(MCRC Non-Clinical) Elucidating progesterone-driven Wnt signalling for breast cancer prevention

Details

Progesterone signalling is essential for normal breast development, but repeated hormone-driven expansion of progenitor cells may also create cellular states that initiate breast tumours. Our recent work (Simões et al, Nature, 2025)shows that blocking progesterone activity in normal human breast tissue reduces Wnt ligand secretion, progenitor activity and collagen-rich extracellular matrix, shifting the tissue away from a cancer-risk-associated state and towards changes that are favourable for breast cancer prevention. This PhD will investigate how progesterone-driven signalling between Wnt5A and its receptor ROR2 regulates epithelial progenitor behaviour, stromal crosstalk and tissue architecture in the human breast, with the long-term goal of identifying pathways that could be targeted for breast cancer prevention.

Across three integrated aims, the student will use complementary human breast models and analytical approaches, including immortalised epithelial and fibroblast models, ex vivo organoid and explant systems, functional perturbation of Wnt signalling, epigenomic profiling and spatial singlecell analysis. First, the student will define how Wnt5A-ROR2 signalling affects epithelial plasticity, luminal progenitor-like activity, fibroblast responses and collagen expression (Aim 1). They will then map progesterone-driven epigenetic changes that regulate Wnt ligands across key epithelial populations (Aim 2). Finally, they will test whether blocking ROR2 signalling or progesteroneinduced epigenetic regulators can reverse progenitor expansion and matrix remodelling in intact human breast tissue models (Aim 3).

The project is directly aligned with the MCRC-CRUK Manchester Centre strategy by addressing early biological events that may precede tumour formation. It will provide outstanding training in cancer prevention biology, hormone signalling, breast tissue models, functional genomics and spatial technologies, while generating mechanistic insight into pathways that could help prevent breast cancer initiation.

Eligibility

You must hold, or about to obtain, a minimum Upper Second Class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. A related master’s degree would be an advantage

International applicants (including EU nationals) should ensure that they meet the academic eligibility criteria for the programme. Applicants who are offered a place will also need to meet the University’s English language requirements before commencing their studies. Further information can be found on the University’s English Language Requirements page.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

Apply directly via this link: https://tinyurl.com/577zjazd or on the online application portal, select MCRC PhD Programme as the programme of study.

You may only apply for one project within this scheme. Please ensure that your application includes all required supporting documents:

• Curriculum Vitae (CV)
• Supporting Statement
• Academic Certificates and Transcripts

Incomplete or late applications will not be considered. Further details are available on our website: CRUK Manchester Centre PhD Training Scheme | Biology, Medicine and Health | University of Manchester

Application Timeline

• Applications open: Monday, 5 October 2026
• Application deadline: Monday, 23 November 2026
• Interview date: Week commencing 11 January 2027
• Start date: September 2027

Equality, diversity and inclusion are central to the University’s activities. The full statement can be found here: https://www.bmh.manchester.ac.uk/study/research/getting-started/equality-diversity-inclusion/

Funding Notes

These studentships are fully funded for four years, covering:

• Project running costs
• University tuition fees (at the UK/Home rate)
• An annual stipend to help with living costs, currently £22,894 a year

International Candidates

We are able to offer a limited number of bursaries to high- performing EU and international candidates, covering PhD fees only. Bursaries do not include financial support for visa/health surcharges. We asses each EU and international candidate’s suitability for a bursary at the application and interview stages.