Overview
Are you interested in research with the potential to improve cancer patients’ safety and clinical outcomes?
Do you want to study in a vibrant multidisciplinary research environment?
Yes? Well, read on, this PhD studentship is for you!
About this opportunity
iCASE industrial partner web link: AstraZeneca – Research-Based BioPharmaceutical Company
Serious, life-threatening adverse drug reactions are a significant problem for cancer patients receiving chemotherapy drugs. They can cause serious harm, even death, and are a major treatment burden for the NHS.
One such example is pneumonitis, or inflammatory interstitial lung disease (ILD). It is an increasingly common severe adverse drug reaction seen in patients receiving systemic anticancer therapies (SACT) including chemotherapeutics, targeted monoclonal antibodies and immunotherapies. Indeed, many patients who experience pneumonitis/ILD, are forced to have a highly effective treatment withdrawn or, worse still, the adverse reaction may prove fatal.
Currently, little is understood regarding the underlying pathogenic mechanisms of SACT-induced pneumonitis/ILD. This studentship will address this significant knowledge gap by building our understanding of the immunological and pathophysiological mechanisms of the reaction and identifying predisposing genetic and non-genetic risk factors. You will use a highly novel approach which will involve the application of both immunological and lung organoid in vitro models.
The proposed studentship supervisory team, consisting of an academic scientist, clinical academic, and pharmaceutical industry scientist, will offer you truly multidisciplinary research training across different research environments. You will be based in the research group of Dr Dan Carr (https://www.liverpool.ac.uk/people/daniel-carr, X: @daniel_f_carr) at the Internationally-renowned Wolfson Centre for Personalised Medicine, Department of Pharmacology and Therapeutics, University of Liverpool. You will receive training in a wide variety of techniques including genetics, molecular biology and advanced primary cell culturing. Under the supervision of Dr Kelly Evans (AstraZeneca) the student will gain valuable experience in cutting edge tissue organoid models, Immunology and safety science in an industry setting. An industrial placement at the AstraZeneca Discovery Centre, Cambridge will provide the student with opportunity to gain hands-on experience within real-world Pharma. Furthermore, this multi-disciplinary training will give you a broad range of laboratory and transferrable skills allowing a wide choice of career options post PhD, both within and outside of academia.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond.
Further information on the programme and instructions on how to apply, including a link to the application portal, can be found on our website https://www.dimen.org.uk/
Further reading
1) Youk J. et al Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2. Cell Stem Cell 2020; Dec 3;27(6):905-919.e10. https://doi.org/10.1016/j.stem.2020.10.004
2) Olsson-Brown A. et al. TNF-α mediated keratinocyte expression and release of matrix metalloproteinase 9: putative mechanism of pathogenesis in Stevens-Johnson syndrome/ toxic epidermal necrolysis. J Invest Dermatol. 2023. Jun; 143 (6):1023-1030.e7. https://doi.org/10.1016/j.stem.2020.10.004
3) Hammond S. et al. Checkpoint Inhibition Reduces the Threshold for Drug-Specific T-Cell Priming and Increases the Incidence of Sulfasalazine Hypersensitivity. Toxicol Sci. 2022; 186(1): 58-69. https://doi.org/10.1093/toxsci/kfab144
4) Choi J. et al. Release of Notch activity coordinated by IL-1β signalling confers differentiation plasticity of airway progenitors via Fosl2 during alveolar regeneration. Nat Cell Biol 2021; 23, 953–966. https://doi.org/10.1038/s41556-021-00742-6
5) Nwikue G. et al. TNF-α mediated keratinocyte expression and release of matrix metalloproteinase 9: putative mechanism of pathogenesis in Stevens-Johnson syndrome/ toxic epidermal necrolysis. J Invest Dermatol. 2023. Jun; 143 (6):1023-1030.e7. 10.1111/1346-8138.16847