Malignant mesothelioma (MM) has an average survival time of less than 12 months post-diagnosis. There is an urgent need to develop novel therapies to treat MM. The fundamental cell-signalling protein ERK5 represents an ideal target to achieve this. We, and others, have shown that ERK5 drives progression of mesothelioma, prostate cancer, colorectal cancer and breast cancer both pre-clinically and in patients. Mechanistically, our lab has demonstrated ERK5 controls tumour progression by sustaining intra-tumoural macrophage populations and maintaining their pro-tumourigenic polarisation. This is crucial since MM is an inflammation-driven cancer with clinical evidence demonstrating that M2-macrophages are associated with decreased overall survival.
Pre-clinical studies demonstrated ERK5 inhibition (via shRNA) induces MM regression in vivo. However, these previous studies have two major caveats 1) they were conducted in models without an intact immune system, so the impact of ERK5 signalling on tumour-associated inflammation could not be properly assessed, 2) they employed shRNA to target ERK5, which is not a valid therapeutic strategy for patients.
Recently, our unpublished work has addressed the limitations of this previous work by using an immune-competent, orthotopic murine model of MM, to reveal as yet undiscovered roles of ERK5 in MM. We have also tested our novel, proprietary inhibitors of ERK5 in MM and we have found them to be very effective.
This project will build on that exciting new data. We will use in vitro model systems and in vivo models to understand underpinning mechanisms and test and understand our drug efficacy, evaluate scheduling regimes and the potential of our new drugs to augment existing standard of care for MM.
Candidates are expected to hold (or be about to obtain) a first class honours degree (or equivalent) in a Biosciences or a related subject. Candidates with experience in Cancer Biology, Biochemistry and Pharmacology are encouraged to apply.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Cancer Sciences.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk
Equality, Diversity & Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/