Overview
Targeted therapies and advanced treatments have revolutionised modern medicine, improving outcomes across cancer, cardiovascular, and autoimmune diseases. However, many of these therapies are limited by unintended toxicity to vital organs such as the liver, heart, and kidneys. Organ injury often compromises therapeutic benefit. Current clinical biomarkers (e.g., ALT, AST, or creatinine) detect damage only after significant tissue injury has occurred, underscoring the urgent need for earlier and more specific molecular indicators of organ stress.
About this opportunity
Our recent transcriptomic analyses reveal that RNAs, especially non-coding RNAs, show distinct expression patterns in response to organ injury. Many of these RNAs are stable, detectable in blood, and may reflect early cellular responses to therapy-induced stress. These findings highlight their potential both as biomarkers for early detection and as regulators of molecular pathways underlying toxicity.
This project will systematically investigate RNA expression changes in therapy-associated organ injury to identify biomarkers and uncover underlying mechanisms of tissue response and repair.
Objectives:
- Identify and validate RNA transcripts consistently associated with organ injury across experimental models and patient datasets.
- Quantify circulating RNAs in plasma and tissue samples, benchmarking their performance against current clinical biomarkers.
- Integrate transcriptomic data with pathway and interaction networks to uncover how RNAs regulate stress, apoptosis, and metabolic adaptation during injury.
- Explore altered RNA processing, localisation, and regulatory roles in cellular models of treatment-induced toxicity.
Experimental Approach and Training:
This interdisciplinary project will combine computational and experimental approaches to deliver a comprehensive understanding of RNA-based mechanisms in organ injury. You will receive training in:
- RNA-seq and small RNA-seq data analysis and integration
- Computational biology and pathway/network analysis
- Experimental modelling of therapy-induced injury in cell-based systems
- Quantitative PCR, RNA localisation, and biomarker validation assays
- Translational and clinical data interpretation
- Molecular and cell biology (CRISPR, immunofluorescence, drug assays, organoid models)
You will work within a collaborative, supportive team that bridges academia, clinical research, and industry, ensuring exposure to both discovery and translational aspects of biomedical science.
Impact:
This will be among the first systematic studies to explore RNA signatures as both biomarkers and mediators of therapy-associated organ injury. The results have the potential to transform how treatment-related toxicity is monitored and predicted, paving the way for safer and more personalised therapeutic strategies.
Benefits of being in the DiMeN DTP:
iCASE industrial partner web link: https://www.tamirna.com
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)Predicting Postoperative Liver Dysfunction Based on Blood‐Derived MicroRNA Signatures. Hepatology (2019) 69:2636-2651, DOI: 10.1002/hep.30572
2)Comprehensive Characterization of Platelet-Enriched MicroRNAs as Biomarkers of Platelet Activation. Cells (2022) 11:1254. https://doi.org/10.3390/cells11081254 *
3) Circulating miRNAs Respond to Denosumab Treatment After 2 Years in Postmenopausal Women With Osteoporosis—the MiDeTe study, The Journal of Clinical Endocrinology & Metabolism (2023) 108:1154–1165, https://doi.org/10.1210/clinem/dgac667
4) A long intergenic non-coding RNA regulates nuclear localization of DNA methyl transferase-1 iScience (2021) 24:102273. doi: 10.1016/j.isci.2021.102273.*
5) Alpha-naphthylisothiocyanate (ANIT) induced changes of miR-200 family in serum and liver of CD-1 mice suggests potential as novel bile duct injury markers. In BRITISH JOURNAL OF PHARMACOLOGY (2023) 180:516-518*
* Publications where PhD students are first authors