Prof Kaye Williams, Dr Katie Finegan
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
The CXCR4/CXCR7-CXCL12 chemokine axis plays a pivotal role in many tumour types and overexpression is associated with disease progression, therapy-evasion and metastasis. Consequently it is a recognised target for anti-cancer therapies. Whilst CXCR4-targeted strategies have been evaluated, evidence suggests cooperativity between CXCR4 and CXCR7 which will limit the effectiveness of targeting either receptor independently. We have unique access to first-in-class dual inhibitors of CXCR4/CXCR7. In preclinical studies we have established that dual inhibition impacts tumour cell growth and migration using in vitro assays in multiple cancer types. This project aims to build upon our promising initial data, extending our understanding of how dual inhibitors of CXCR4/CXCR7 may be developed as anticancer therapies to improve patient outcome.
The studies are spread across three work packages. The first is in vitro and focuses on evaluating the impact of CXCR4/CXCR7 inhibition of proliferation, drug response and metastatic characteristics using aggressive tumour models in 2D and 3D culture systems. We will then use the obtained data to design and take forward in vivo studies using orthotopic xenograft tumours. Attention will be paid not only to the therapeutic response of primary disease but also metastases- the key transition point that accounts for loss of life in most cancer patients and an area of significant unmet need. Finally the CXCR4/CXCR7-CXCL12 axis plays a role in the systemic immune system and there is a potential for targeting to impact significantly on the tumour immune landscape. This will be explored by evaluating immune cell infiltrates and cytokine signalling in syngeneic and xenograft tumours that between them enable analysis of the full complement of immune cells. Together these data will support development of CXCR4/CXCR7-CXCL12 targeting towards clinical application, whilst providing fundamental understanding of how effects are elicited and how CXCR4/CXCR7 may be best exploited in combined (immune) therapy approaches.
Entry Requirements
Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in relevant subject. A related master’s degree would be an advantage.
Funding Notes
The Studentship will cover an annual stipend (currently at £19,000 per annum), running expenses and PhD tuition fees at UK/EU rates. Where international student fees are payable, please provide evidence within your application of how the shortfall will be covered (approximately £17,000 per annum).
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
Continue with Facebook
