James Dear

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My research in a nutshell

My overall objective is to make medicines safer for patients. To achieve this we focus on discoverying new tools that can identify side-effects rapidly and develop new treatments for drug-induced organ injury.

We have a particular focus on microRNA. Until relatively recently 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 biomarkers for 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 across the UK. We are also developing novel treatments for those patients at high risk of liver failure, a group without effective treatments.

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.

                                                                                                                  

Education/Academic qualification

Medicine, Bachelor of Medicine and Bachelor of Surgery, Univ Oxford

Award Date: 1 Jun 1999

Pharmacology, Doctor of Philosophy (PhD), University College London

Award Date: 1 Oct 1996

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