PhD Studentship: Modelling New Therapeutic Approaches for Neoadjuvant Treatment of High Grade Serous Ovarian Carcinoma

Overview

Professor James Brenton wishes to recruit a student to work on the project entitled: "Modelling new therapeutic approaches for neoadjuvant treatment of high grade serous ovarian carcinoma".

This is a unique opportunity for PhD study in the world-leading Cancer Research UK Cambridge Institute (CRUK CI), to start a research career in an environment committed to training outstanding cancer research scientists of the future.

If you are interested in finding out more about our groundbreaking scientific research, please visit our website at https://www.cruk.cam.ac.uk/

Project details

High-grade serous ovarian carcinoma (HGSC) is molecularly characterised by extreme chromosomal instability which presents a major barrier to personalized therapy. Most patients with HGSC in the UK receive neoadjuvant chemotherapy but this has particularly poor outcome because of: (1) suboptimal therapeutic effects and (2) rapid acquisition of drug resistance. The major need is to develop new clinical trials with agents that minimize these deleterious effects. We are using integrative approaches to address these problems using genomic and functional characterization of clinical trial samples together with patient-derived organoid and xenograft (PDX) models. We have developed whole genome sequencing (WGS) methods that provide copy number signatures that classify HGSC based on mutational processes. With these methods we have generated large WGS data sets that are being used to design clinically relevant immunocompetent mouse models using in vivo CRISPR recombination.

The aim of the project is to develop new therapeutic approaches for neoadjuvant therapy of BRCA1 mutated HGSC. These patients have adverse outcomes despite initial response to platinum-based chemotherapy and PARP maintenance treatment. The project will focus on modifiers of chemotherapy induced senescence and combination therapy with new drugs targeting DNA damage response. The experimental approach will combine cell fate analysis using in vitro and in vivo lineage tracing using existing PDX and CRISPR engineered models that can evaluate coincident immunological responses. Pharmacodynamic effects on the DNA damage response pathways will be measured using single cell technologies, including CyTOF and imaging mass cytometry of pre-clinical models and patient samples. From this work we expect to deeply characterize tumour cell clonal evolution and adaptations to these treatment combinations which will guide the design of new clinical trials for HGSC.

The successful candidate can expect to develop innovative skills in both computational and experimental approaches. The project will be closely aligned with two post-doctoral workers focusing on mouse models and one computational post-doctoral worker with extensive WGS experience.

Eligibility

We welcome applications from both UK and overseas students.

Applications are invited from graduates or final-year undergraduates who hold or expect to gain a First/Upper Second-Class degree (or equivalent) in a relevant subject from any recognised university worldwide.

Applicants with relevant research experience, gained through Master's study or while working in a laboratory, are strongly encouraged to apply.

How to apply

Please apply via the ‘Apply’ button above.

For further information about the course and to access the Applicant Portal, visit:
https://www.postgraduate.study.cam.ac.uk/courses/directory/cvcrpdmsc You should select to commence study in Michaelmas Term 2025 (October 2025).

More information can be found here: PhD studentship: Modelling new therapeutic approaches for neoadjuvant treatment of high grade serous ovarian carcinoma - Job Opportunities - University of Cambridge

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