Prof Sara Zanivan
Dissecting tumour stroma heterogeneity in high grade serous ovarian cancer using cutting edge mass spectrometry proteomics approaches
As a world-leading cancer research centre, the CRUK Beatson Institute supports cutting edge work into the molecular mechanisms of cancer development. We provide an outstanding research environment, underpinned by state-of-the-art core services and advanced technologies with special emphasis on imaging and in vivo models.
We are looking for students with a very good degree in a Life Sciences subject and an aptitude for experimental work, who are also highly committed to pursuing a PhD and a career in cancer research. The Beatson has an excellent reputation and success record in training its graduate students. Students, whilst being trained at the Institute working within our research groups, will matriculate with the University of Glasgow.
Our PhD studentships are for a maximum of 4 years, and currently provide students with an annual stipend of £19,000 and matriculation fees for home, EU or overseas students.
The High grade serous (HGS) ovarian cancer is the deadliest gynaecological cancer due to the limited availability of targeted therapies against the cancer cells, because only few targetable recurrent mutations have been identified in these cells. HGS ovarian tumours have an extensive cancer-associated fibroblast (CAF)-rich stroma that largely interact with cancer and immune cells. CAFs play fundamental roles in tumour malignancy. They have been shown to influence the phenotype of cancer and immune cells, as well as therapy resistance, and have emerged as an attractive alternative therapeutic target. However, what the molecular mechanisms behind these functions are, whether they are conserved at different metastatic sites, and whether they are targetable is still largely unclear. This project will start tackling these questions using cutting edge technologies and relevant HGS ovarian cancer patient samples.
The student will use laser-capture microdissection and state-of the art MS proteomics technologies to spatially assess the proteome of the stroma of HGS ovarian tumours. Data will be integrated with tumour features such as presence/absence of immune cells and proximity of cancer cells, to identify stromal signalling potentially involved in shaping cancer and immune cell behaviour important to support tumour malignancy and resistance to therapy. Metabolic pathways will be a major focus of the data analysis. Key findings will be functionally investigated with knock-out and over-expression techniques using patient-derived cells and relevant in vitro co-culture models already established in the Zanivan group. Final findings may be further validated in in vivo models.