Patricia Roxburgh, University of Glasgow; Prof Karen Blyth, CRUK Scotland Institute & Prof Colin Semple, University of Edinburgh
Project Description
There are 7500 new ovarian cancer cases in the UK per year making it the 6th most common cancer in females. Although ovarian cancer survival is improving, 5-year survival rates remain poor (42.6%). High-grade serous ovarian cancer (HGSOC) is the most common and lethal form of ovarian cancer. It is characterised by almost ubiquitous TP53 aberrations, cell-cycle defects, huge copy number change and genomic instability. We recently demonstrated two pathways to genomic diversity in HGSOC (1). One (approximately 50% of patients) is through homologous recombination deficiency (HRD); these tumours largely respond to platinum/PARP inhibitors. The other group of cancers is characterised by whole genome duplication (WGD) and is associated with chromothripsis, extrachromosomal DNA harbouring oncogenes, mitochondrial DNA mutations and CCNE1 amplification; these tumours are less likely to benefit from platinum/PARPi therapy and therefore understanding and developing effective therapies for this HGSOC sub-group is a major unmet need.
Genetically engineered mouse models of selected types of HGSOC have already been developed. To date they represent BRCA1/2 driven, HRD, HGSOC reasonably well however no model exists that recapitulates the structural genomic diversity seen in the poorest prognostic HGSOC sub-groups. In this project we therefore plan to develop novel, patient-relevant models of WGD HGSOC. Activation of mutational events seen in WGD HGSOC such as ecDNA-Myc, CCNE1 and mitochondrial mutations will be recapitulated in mouse models which will then be fully characterised to ensure that they are representative of the corresponding sub-type in humans, from a pathology, molecular and disease spectrum angle. Then after understanding the model and disease progression, we will use these realistic models to test rational treatments in an effort to identify new, more effective treatment strategies for this poor prognostic sub-group of patients.
Skills/Techniques that will be gained
The student will work in Professor Blyth’s group which is world leading in the development of mouse models of cancer and attached to the MRC National Mouse Genetics Network. The student will also be supported by Professor Semple from University of Edinburgh who is a bioinformation with expertise in structurally diverse cancers (mesothelioma and ovarian cancer) and Professor Patricia Roxburgh who has expertise in treatment of ovarian cancer and development of new cancer therapeutics, and who will ensure clinical relevance to the project.
The student will gain expertise in development and analysis of genetically engineered mouse models of cancer, translational preclinical models, immunohistochemistry, genomics and computational methods to interrogate biological data. They will also access the research training programme provided by the Universities of Glasgow and Edinburgh and actively participate in the ovarian theme of the CRUK Scotland Centre including attending regular joint Edinburgh-Glasgow meetings and presenting their findings internally and externally at conferences.
For further information on the project or informal enquiries, please contact Prof Patricia Roxburgh, This email address is being protected from spambots. You need JavaScript enabled to view it.
When submitting your application please also upload the completed EDI recruitment form.
To place an application, please visit this site at the University of Glasgow. Please note that due to funding requirements this opportunity is open to UK applicants only.
Duration: 4 years, starting October 2026
Closing Date: Wednesday 6th May 2026
Interview for this position will take place in June 2026
Lab Websites
References
Divergent trajectories to structural diversity impact patient survival in high grade serous ovarian cancer A. Ewing, A. Meynert, R. Silk, S. Aitken, D. P. Bendixsen, M. Churchman, et al. Nat Commun 2025 Vol. 16 Issue 1 Pages 5586
Engineered extrachromosomal oncogene amplifications promote tumorigenesis Davide Pradella, Minsi Zhang, Rui Gao, Melissa A. Yao, Katarzyna M. Gluchowska, Ylenia Cendon-Florez, Tanmay Mishra, Gaspare La Rocca, Moritz Weigl, Ziqi Jiao, Hieu H. M. Nguyen, Marta Lisi, Mateusz M. Ozimek, Chiara Mastroleo1, Kevin Chen1, Felix Grimm, Jens Luebeck, Shu Zhang, Andrea Alice Zolli, Eric G. Sun, Bhargavi Dameracharla, Zhengqiao Zhao, Yuri Pritykin, Carlie Sigel, Howard Y. Chang, Paul S. Mischel, Vineet Bafna, Cristina R. Antonescu & Andrea Ventura Nature. Jan 2025
Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer. Paffenholz SV, Salvagno C, Ho YJ, Limjoco M, Baslan T, Tian S, Kulick A, de Stanchina E, Wilkinson JE, Barriga FM, Zamarin D, Cubillos-Ruiz JR, Leibold J, Lowe SW. Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2117754119.
PARP Inhibitor Maintenance After First-Line Chemotherapy in Advanced-Stage Epithelial Ovarian Cancer: A Systematic Review and Meta-Analysis Petousis S, Kahramanoglu I, Appenzeller-Herzog C, Angeles MA, Margioula-Siarkou C, Kacperczyk-Bartnik J, Bilir E, Chatzakis C, Caruso G, Bizzarri N, Dinas K, Bowtell DDL, Garsed DW, Ray-Coquard I, Ledermann JA, Friedlander M, Sotiriadis A, Heinzelmann-Schwarz V, Zwimpfer TA. JAMA Netw Open. 2025 Nov 3;8(11):e2541648