About
Drug safety and the mitochondria: toxicological target to personal susceptibility factor
My research group, the “Bioenergetics Group”, within the Department of Pharmacology & Therapeutics at the University of Liverpool, has a translational focus on investigating the role of mitochondria dysfunction in drug safety. We strive to develop physiologically and pharmacologically relevant 2D and 3D models and methods with which to define the molecular mechanisms of mitotoxins and their relative potential to induce human toxicity and have collaborated widely with the pharmaceutical industry in this area. In addition, we also investigate how individuality in mitochondrial function and mitochondrial genotype may influence patient susceptibility to mitotoxins. Recently, we have performed innovative research to define variations in bioenergetic phenotype in human liver tissue in order to build a computational model to predict mitotoxicity. We have also created a panel of novel HepG2 transmitochondrial cybrids as a personalised model of mitochondrial genotype. Each cybrid line contains a different mitochondrial genome, against a stable nuclear background. Current projects in the group investigate the influence of mitochondrial function on drug safety across several organs including bone, muscle, kidney, heart and liver. I have also established the Seahorse Respirometry Facility at Liverpool, which is a hub for collaborative projects across the University and externally, and we are at the forefront of pushing the boundaries of this technology into primary tissue interrogation and translational clinical studies. I believe that the influence of personal mitochondrial phenotype and genotype is an important and exciting new frontier in pharmacology & toxicology.
Prizes
I have received awards from the British Toxicology Society, including the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) Lectureship (2023) and the Early Career Toxicologist Prize (2017).
Editorial Positions I am an Executive Editor for the British Journal of Clinical Pharmacology and Editorial Board member for Toxicology Research.
Top 3 Papers
Ball AL, Jolly CE, Lennon MG, Lyon JJ, Alfirevic A, & Chadwick AE (2023). The generation of HepG2 transmitochondrial cybrids to reveal the role of mitochondrial genotype in idiosyncratic drug-induced liver injury. eLife 12
Ball AL, Bloch KM, Rainbow L, Liu X, Kenny J, Lyon JJ, Alfirevic A, Chadwick AE. (2021). Assessment of the impact of mitochondrial genotype upon drug-induced mitochondrial dysfunction in platelets derived from healthy volunteers. Arch Toxicol 95: 1335-1347
Jolly CE, Douglas O, Kamalian L, Jenkins RE, Beckett AJ, Penman SL, Williams DP, Monshouwer M, Simic D, Snoeys J, Park BK, Chadwick AE (2020). The utility of a differentiated preclinical liver model, HepaRG cells, in investigating delayed toxicity via inhibition of mitochondrial-replication induced by fialuridine. Toxicol Appl Pharmacol 403.
Prizes or Honours
- Early Career Investigator Prize (The British Toxicology Society, 2017)
- Poster Prize (Gordon Conference, 2011)
- IVTS Poster Prize (In Vitro Toxicology Society, 2010)
Funded Fellowships
- The Gordon Gibson Memorial Travel Fellowship (The British Toxicology Society, 2011)