Elucidating progesterone-driven Wnt signalling for breast cancer prevention
Closing date: 23/11/2026
Non-Clinical Studentship Project: Elucidating progesterone-driven Wnt signalling for breast cancer prevention
Lead Supervisors: Dr Bruno Simoes
Co-Supervisors: Professor Robert Clarke, Dr Sankari Nagarajan, Professor Sacha Howell
Applications Deadline: 12:00pm Monday 23rd November 2026
Interviews: Friday 5th February 2027 (in Manchester)
Start date: September 2027
Project Keywords: Breast cancer prevention; progesterone signalling; Wnt/ROR2 pathway
Research Opportunity: Non-Clinical Studentship leading to the award of PhD
Project Outline
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 epithelialpopulations (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.
Applications for this project are now open. Please complete your application on The University of Manchester website.
About Dr Bruno Simoes (project Lead Supervisor)
Dr Bruno Simões is the Senior Research Fellow at the recently launched Prevent Breast Cancer Research Unit at the University of Manchester. He graduated in Microbial Biology and Genetics from the University of Lisbon, which included a research training year in Italy. He then completed his PhD in Spain, where he investigated the effects of estrogen on human breast stem cells. In 2011, he joined the University of Manchester to study the role of breast cancer stem cells in resistance to endocrine therapy in estrogen receptor-positive tumours. His work generated pre-clinical data that established the basis for a clinical trial in anti-estrogen resistant metastatic breast cancer.
In his current role, Bruno leads laboratory investigations using normal breast tissue obtained from breast cancer prevention clinical studies. His research aims to understand the biological mechanisms underlying breast cancer risk by identifying the earliest molecular and cellular alterations in tumour-initiating luminal progenitor cells. Through this work, his group aims to develop improved chemoprevention strategies for women at increased risk of breast cancer and has already demonstrated that inhibition of progesterone receptor signalling can target key biological determinants of breast cancer risk (Simões et al., Nature, 2025).
Key information
Before submitting an application, please ensure you have read the information below about the funding arrangements and eligibility for Non-Clinical Studentships.
We also encourage you to get in contact with the lead supervisor to discuss the project and any particulars.
Further information is available on the Non-Clinical PhD Studentships webpage.
Our Non-Clinical PhD Studentships are usually funded for four years, with funding covering:
- Project running costs
- University tuition fees university tuition fees (at the UK rate, with some scholarships available for high-performing EU/International candidates)
- An annual stipend of £22,500 to help with living costs
Studentships are highly competitive and so we encourage you to contact any supervisors who you are interested in working with before applying for our Non- Clinical PhD Studentships.
International Candidates
The University of Manchester aims to support the most outstanding applicants from outside the UK.
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 assess each EU and international candidate’s suitability for a bursary at the application and interview stages.
You must hold, or be about to achieve, a First or Upper Second-class honours degree in a relevant subject. A related Master’s degree is also an advantage.
International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University’s Country Specific information page.
Applications for this programme are now open. Please submit your application on The University of Manchester application portal.
Key dates
- Applications open: Monday 5th October 2026
- Application deadline (all projects): 12:00pm Monday 23rd November 2026
- Non-Clinical Interviews: Friday 15th January 2027 (in Manchester)
- Start date: September 2027
Useful Links
Submit your application
Interested in applying for this opportunity? Submit your application on The University of Manchester application portal.
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