Role of CAF metabolism in ovarian cancer
Prof Sara Zanivan, Tumour Microenvrionment and Proteomics
High grade serous (HGS) ovarian cancer is the most lethal gynaecological disease. While initial response to treatment is promising, the majority of patients develop resistance to chemotherapy. Targeted therapies against cancerous cells are limited because only a few genetic driver mutations are recurrent1.
HGS ovarian tumours contain vast amounts of stroma, which is highly populated by cancer-associated fibroblasts (CAFs). CAFs play an active role in tumour progression, metastasis, and treatment response. The CAFs’ ability to secrete a plethora of soluble factors and produce aberrant extracellular matrix2-4 alter the tumour microenvironment (TME) and influence the behaviour of cancer and other stromal cells. There is increasing evidence, including on-going work in our team, that the metabolism of CAFs supports their ability to create an aberrant TME and facilitates tumour progression.
Using CAFs derived from HGS ovarian cancer patients and organotypic cultures this project aims to understand how CAF metabolism controls their ability to create an aberrant TME and promote cancer pathology.
The candidate will develop skills in primary cell cultures, heterotypic co-cultures, CAF-derived extracellular matrix production and functional assessment, state-of the art mass spectrometry (MS) proteomics (sample preparation and processing, and data analysis), MS-metabolomics and other assays to assess cell metabolism, imaging analysis.
For informal enquiries, please email Prof Sara Zanivan (email@example.com)
To apply, please complete a PhD Studentship Form (in right-hand menu opposite). Application deadline: 3rd January 2020
1. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer. 2015 Nov;15:668-79.
2. Cancer Associated Fibroblasts: The Architects of Stroma Remodeling. Proteomics. 2018 Mar;18:e1700167.
3. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity. Nat Commun. 2017 Feb 15;8:14206.
4. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Sci Signal. 2019 Feb 5;12. pii: eaan8247