Josh Gardner

0151 794 5767

Institute of Translational Medicine University of Liverpool

Supervisor: Professor Dean Naisbitt

During my time studying Medical Biochemistry at Swansea University I had always been particularly fascinated by adverse drug reactions (ADRs) and the mechanisms behind both pharmacological and toxic effects from a biochemical standpoint. It was interesting to learn how our understanding ADRs can be translated into the development predictive models in order to inform on the design of safe and efficacious drugs. I therefore studied modules relevant to my interests including pharmacology, immunology, techniques in molecular biology and medical genetics. I completed a final year project involving the assessment of DNA damage via the use of flow cytometry. I tested genotoxic chemicals such as carcinogens hazardous to human health and carried out analysis using different scoring platforms such as ImageStream®, Metafer™ and manual scoring with light and fluorescent microscopes. My interest in ADRs developed significantly during completion of an MRes in Biomedical Science and Translational Medicine within the University of Liverpool’s Centre for Drug Safety Science. My work in the CDSS involved studying the mechanisms of drug-induced liver injury, specifically mitochondrial toxicity, of potentially hepatotoxic drugs.

Project Title: Exosomes act as endogenous messengers transferring signals between tissue cells and the immune system

Exosomes are small membrane micro vesicles released by cells, and present in almost all biological fluids. They are believed to play an important role in intercellular communication and immune regulation. Recently, an increase in exosomal albumin mRNA has been observed in drug-treated hepatocytes. In recent studies we have identified two distinct patterns of cross-talk between tissue cells and dendritic cells:1, stress-induced signalling; and 2, a non-stress related signalling, with both pathways resulting in unique dendritic cell cytokine profiles. Mass spectrometry has also identified over 500 hepatocyte-derived proteins within exosomes, some of which are modified with drugs. Thus, selective packaging of tissue-derived exosomes may be an important factor in regulating drug-specific immune responses. The hypothesis of the project is that drug exposure determines the selective packaging of hepatocyte and keratinocyte-derived exosomes, which regulates the adaptive immune response through dendritic cell signalling. The project involves an industrial partner (AstraZeneca, Cambridge) where time will be spent within the department of Drug Safety and Metabolism.

Other activities

Public engagement at Bluedot festival – Talking to the public about the importance of the immune system.

UKDAN Annual conference -Liverpool

DX toxicology conference – Alderley edge

This website uses cookies to ensure you get the best experience on our website.