James Dear
Reader

Contact details
- Email: james.dear@ed.ac.uk
Address
- Street
-
Queen's Medical Research Institute
47 Little France Crescent
Edinburgh BioQuarter - City
- Edinburgh
- Post code
- EH16 4TJ
Research summary
My overall objective is to improve the diagnosis and management of acute medical emergencies by understanding the role and clinical utility of circulating microRNAs. Less than 10 years ago their existence in the circulation was unknown - now microRNAs are recognized to provide a huge reservoir for disease biomarker discovery and a mechanism for signalling between cells that is amenable to therapeutic intervention. My research combines knowledge enhancement with a clear translational pathway that aims to improve health and develop diagnostic and therapeutic products with Scottish, UK and worldwide commercial partners. We focus specifically on microRNA biomarkers in drug toxicity, which has great importance to both clinical patient care and commercial drug development. Paracetamol (acetaminophen) overdose is one of the most common reasons for emergency hospital attendance and the leading cause of acute liver failure in the Western world. Annually in the UK, paracetamol overdose results in approximately 100,000 Emergency Department presentations and 50,000 acute hospital admissions and is the direct cause of death in around 150 people. We have developed markers that promise to transform the clinical care of this large patient group. Our biomarkers allow early exclusion of liver injury and facilitate prompt identification of injury that will progress despite current treatment. Improved identification of drug-induced liver injury is also of great importance to the pharmaceutical industry in the UK and worldwide. To drive forward our research I have partnered with pharma to translate my academic research into commercial benefit and safer medicines for the public. In parallel with this biomarker program, we have developed a new shorter and safer treatment protocol for paracetamol overdose that is now being used in Edinburgh, with a plan for roll out across the UK. This promises to free up an estimated 20,000 UK acute hospital bed-days/year, clear evidence of impact ahead of REF2020. My research group has established a portfolio of pre-clinical models (cell, zebrafish and rodent) that explore the role of microRNAs in toxicology and in cell-to-cell signaling. For example, we have recently developed a new zebrafish model of liver toxicity and performed RNAseq on small and mRNA fractions to identify novel disease pathways. Urine contains extra-cellular vesicles enriched with microRNA that are called exosomes. They are released from the cells that line the glomerulus and kidney tubules. This allows us to use the kidney as a model organ to study exosome mediated signaling in health and disease, in vitro and in vivo.
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Duration of consultant experience and patient outcome following acute medical unit admission.: An observational cohort study
In:
Clinical Medicine
Research output: Contribution to Journal › Article (Accepted/In press) -
Amplification-free electrochemical biosensor detection of circulating microRNA to identify drug-induced liver injury
In:
Biosensors & Bioelectronics, vol. 231
DOI: https://doi.org/10.1016/j.bios.2023.115298
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Tandem Mass Tag-Based Quantitative Proteomic Profiling Identifies Novel Serum Biomarkers of Drug-Induced Liver Injury in Humans
In:
Nature Communications, vol. 14, pp. 1215
DOI: https://doi.org/10.1038/s41467-023-36858-6
Research output: Contribution to Journal › Article (Published) -
Endothelin blockade prevents the long-term cardiovascular & renal sequelae of acute kidney injury
In:
Science Translational Medicine
DOI: https://doi.org/10.1126/scitranslmed.abf5074
Research output: Contribution to Journal › Article (Published) -
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage
In:
Nature Communications, vol. 13
DOI: https://doi.org/10.1038/s41467-022-34262-0
Research output: Contribution to Journal › Article (Published) -
Arterial stiffness, endothelial dysfunction and impaired fibrinolysis are pathogenic mechanisms contributing to cardiovascular risk in ANCA-associated vasculitis
(12 pages)
In:
Kidney International, vol. 102, pp. 1115-1126
DOI: https://doi.org/10.1016/j.kint.2022.07.026
Research output: Contribution to Journal › Article (Published) -
Small interfering RNA: Discovery, pharmacology and clinical development—An introductory review
In:
British Journal of Pharmacology
DOI: https://doi.org/10.1111/bph.15972
Research output: Contribution to Journal › Review article (Published) -
An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis (DEFINE): A Phase Ib/IIa Randomised Controlled Trial
In:
American Journal of Respiratory and Critical Care Medicine
DOI: https://doi.org/10.1164/rccm.202203-0477OC
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Investigation of a relationship between serum concentrations of microRNA-122 and alanine aminotransferase activity in hospitalised cats
In:
Journal of Feline Medicine and Surgery, vol. 24, pp. e289-e294
DOI: https://doi.org/10.1177/1098612X221100071
Research output: Contribution to Journal › Article (Published) -
Investigation of a relationship between serum concentrations of microRNA-122 and ALT activity in hospitalised cats
In:
Journal of Feline Medicine and Surgery
DOI: https://doi.org/10.1177/1098612X221100071
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Proximity sensitive detection of microRNAs using electrochemical impedance spectroscopy biosensors
In:
Biosensors & Bioelectronics, vol. 212
DOI: https://doi.org/10.1016/j.bios.2022.114404
Research output: Contribution to Journal › Article (Published) -
Microfluidic system for near-patient extraction and detection of miR-122 microRNA biomarker for drug-induced liver injury diagnostics
(13 pages)
In:
Biomicrofluidics, vol. 16
DOI: https://doi.org/10.1063/5.0085078
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Randomised Controlled Trial of Intravenous Nafamostat Mesylate in COVID pneumonitis: Phase 1b/2a Experimental Study to Investigate Safety, Pharmacokinetics and Pharmacodynamics
In:
EBioMedicine
DOI: https://doi.org/10.1016/j.ebiom.2022.103856
Research output: Contribution to Journal › Article (Published) -
Regular acetaminophen use and blood pressure in people with hypertension The PATH-BP Trial
In:
Circulation
DOI: https://doi.org/10.1161/CIRCULATIONAHA.121.056015
Research output: Contribution to Journal › Article (Published) -
Towards quantitative point of care detection using SERS lateral flow immunoassays
In:
Analytical and bioanalytical chemistry
DOI: https://doi.org/10.1007/s00216-022-03933-8
Research output: Contribution to Journal › Review article (Published) -
Comment on Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients
In:
Clinical Toxicology
DOI: https://doi.org/10.1080/15563650.2021.2009849
Research output: Contribution to Journal › Letter (Published) -
Evaluation of new or repurposed treatments for COVID-19: protocol for the phase 1b/2a DEFINE trial platform
In:
BMJ Open
DOI: https://doi.org/10.1136/bmjopen-2021-054442
Research output: Contribution to Journal › Article (Published) -
Evaluation of new or repurposed treatments for COVID-19: protocol for the phase Ib/IIa DEFINE trial platform
(16 pages)
In:
BMJ Open, vol. 11
DOI: https://doi.org/10.1136/bmjopen-2021-054442
Research output: Contribution to Journal › Article (Published) -
Introduction to a series of Pro/Con papers in Clinical Toxicology
In:
British Journal of Clinical Pharmacology
DOI: https://doi.org/10.1111/bcp.15128
Research output: Contribution to Journal › Editorial (E-pub ahead of print) -
Simultaneous Detection of Drug-Induced Liver Injury Protein and microRNA Biomarkers Using Dynamic Chemical Labelling on a Luminex MAGPIX System
In:
Analytica
DOI: https://doi.org/10.3390/analytica2040013
Research output: Contribution to Journal › Article (Published)