Cancer Research UK funded Clinical Research Fellowship: The interplay between chemical and mechanical signalling in PDAC

We are now accepting applications for our Cancer Research UK funded Clinical Research Fellowships to start in September 2019.

Our Cancer Research UK funded Clinical Research Fellowship provide up to 3 years’ support for clinically qualified professional to undertake research training within Barts Cancer Institute.

This training programme, part of a multi-million pound award from CRUK, aims to develop a cohort of medically qualified scientists equipped both intellectually and technically to conduct the highest quality research on cancer.

The scheme is designed to accommodate the dual clinical-research training career path by allowing fellows to spend a portion of their time on NHS sessions

Fellows will be appointed as a Clinical Research Fellow with the Institute and will be required to register for a PhD, based on research undertaken during the fellowship.

Project Outline:
Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive cancer of unmet needs with a 5-year median survival rate of <5%. Oncogenic KRAS mutations are the main drivers of PDAC, accounting for more than 90% of all diagnosed PDAC cases. The major pro-proliferative signalling pathway downstream of mutant KRAS in PDAC is the RAS-MAPK pathway. However, therapeutic targeting of the RAS-MAPK pathway in PDAC has shown limited efficacy in vivo. Importantly, our preliminary findings suggests that the mechanical properties of the PDAC micro-environment can have a substantial effect on the sensitivity of the tumour cells to RAS-MAPK inhibition. In particular, the stiffness of the surrounding matrix seems to act as a crucial factor in determining the sensitivity to RAS-MAPK signalling inhibition. The aim of this project is to determine at a molecular level how mechanical cues from the micro-environment are sensed by PDAC tumour cells, and how such signals confer resistance to inhibition of RAS-MAPK signalling. We will then assess if perturbing the sensing of mechanical cues in PDAC cells can act as a tool to sensitise PDAC cells to targeted therapy agents against the RAS-MAPK signalling.

In this project, the PhD candidate will learn to work with in vitro and in vivo models of PDAC, and use various cell culture, genetic, as well as protein biochemistry based tools to evaluate the cross-talk between the RAS-MAPK and mechano-sensing pathways in PDAC.

For more information, including entry requirements and how to apply, please see:
https://www.bci.qmul.ac.uk/en/study-with-us/postgraduate-research/cruk-clinical-research-fellowships-2019-20