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  Characterising macrophage phenotypes and functions in the transition from pre-malignant lesions to endometrial cancer


   Centre for Reproductive Health

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  Dr Takanori Kitamura , Dr Florent Petitprez, Mr Neil Ryan  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Endometrial intraepithelial neoplasia (EIN) is a precancerous condition that significantly increases the risk of developing endometrioid endometrial cancer (EEC), a global health concern as EEC is the most common gynaecologic malignancy with a rapidly rising incidence. Given EEC’s poor clinical outcomes, especially in late-diagnosed cases, tools for risk assessment and management of EIN progression are urgently needed.Loss of PTEN and ARID1A in endometrial epithelium has been reported to drive the development and progression of EIN. Beyond these intrinsic tumour cell changes, tumour-associated macrophages (TAMs) are thought to facilitate tumour progression by promoting invasion and suppressing immune responses. Since distinct TAM subsets localize to specific tumour regions and adapt their phenotypes to environmental factors, understanding their characteristics in EIN/EEC could offer novel biomarkers for predicting tumour progression. However, EEC research faces chronic underfunding, leaving the immune landscape of EIN largely unexplored.

This project aims to elucidate changes in TAM phenotype and localisation during endometrial tumour progression associated with PTEN and ARID1A deficiencies. Additionally, we will investigate potential impact of distinct TAM subsets on the status of anti-tumour immune cell (e.g., CD8+ T cell and NK cell).

The student will undertake focused work packages:

1. Define transcriptome of TAM subsets and anti-tumour immune cells within EIN and EEC: The student will analyse public bulk and single-cell RNA sequencing data sets. Additionally, they will conduct single-nuclei RNA sequencing on archived tumour samples.

2. Reveal the localisation of TAM subsets and anti-tumour immune cells within neoplastic regions of EIN and EEC: The student will conduct multiplex immunostaining on a large cohort of tumour samples and combine results from work package 1 with an in-house dataset of endometrial cancer spatial transcriptomics.

3. Investigate the functional impact of tumour cells on macrophage phenotype: The student will develop PTEN and/or ARID1A knockout human endometrial cells to model EIN and EEC. Effects of these cells on the phenotype of human macrophages derived from human pluripotent stem cells (iPSC) or blood monocytes will be explored by flow cytometry and bulk RNA sequencing.

This study will reveal immune cell profiles, particularly TAM subsets, linked to the progression of EIN into EEC. The findings would lead to new biomarkers for predicting EEC progression and response to immunotherapy. During this PhD, the student will have the opportunity to acquire solid foundational knowledge on tumour immunology and its clinical applicability, as well as practical skills in both wet lab and computational approaches.

PhD programme in Reproductive Health and Science

This 3.5 year studentship programme is based at the Centre for Reproductive Health (CRH) within the Institute for Regeneration and Repair (IRR).

 Students will receive cross-disciplinary training aimed at equipping graduates with skills to drive future research developments in reproductive science and health. At the end of 3 years of PhD study, 0.5 years of funding is available to support approved activities that enable student career progression.

Applicants are encouraged to contact Dr Takanori Kitamura - [Email Address Removed]

 Students will benefit from the world-leading research at the CRH, which is led by a combination of non-clinical and clinician scientists. Students will be integrated into the broader CRH PhD programme, providing exposure to diverse aspects of Reproductive Health, and be embedded in the IRR’s Postgraduate Training Framework. Students will have access to state-of-the-art research facilities at IRR and the wider University, and benefit from a broad range of training opportunities which are available across The University of Edinburgh campus. Training in Edinburgh: Edinburgh has a wide range of training opportunities, from those aimed at acquisition of general research skills and transferable skills (Institute for Academic Development) to advanced training courses in specific areas (e.g. image analysis, analysis of transcriptomic data sets).

Full eligibility criteria and further details about the PhD studentships and application process as below, but these studentships are only to support non-clinical students. University of Edinburgh adheres to equality, diversity and inclusion principles.

This opportunity is open to UK and international students and provides funding to cover stipend (maintenance allowance at UKRI rate, which was £19,237.00 for 24-25 and tbc for 25-26) and tuition fees. Applicants are expected to have a good honours degree in the sciences at least UK level of 2.1 or the equivalent from non-UK universities and must meet the English language entry requirements. A Master’s degree in a relevant life sciences subject would be an advantage.

HOW TO APPLY

Required

•   Personal statement (1 page in total) covering why you want to apply for a specific project(s), how your career to date has prepared you to do this PhD, and how gaining this PhD will meet your long-term career goals.

•   Curriculum Vitae (maximum 2 pages)

•   Two academic references using PhD programme reference form - CRH 2025 submitted by the referee by the deadline

Optional

Where applicable 0.5 extra pages can be used to explain any exceptional circumstances that may have affected academic performance to date, non-linear career paths, or any other information we may find useful in ensuring adherence to the principles of equality, diversity and inclusion - This is optional and it is anticipated that the many applicants will not need to provide this additional document.

Applications should be sent to Aga Wysocka [Email Address Removed]

Interviews

Interviews will be in the format of a 7 min presentation by the applicant on a previous/on-going research project that showcases skills and knowledge.

This will then be followed by questions on the presentation and their application. The interview - 45 minutes is taking place on Microsoft Teams.

Biological Sciences (4) Mathematics (25)

Funding Notes

This opportunity is open to UK and international students and provides funding to cover stipend (maintenance allowance at UKRI rate, which was £19,237.00 for 2024-2025 and to be confirmed for 2025-2026) and tuition fees.


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