LOCATION:

NHS Blood and Transplant (NHSBT) Blood Donor Centre, John Radcliffe Hospital, Oxford, OX3 9BQ

Benedikt Kessler, Professor of Biochemistry and Mass Spectrometry  

TDI Mass Spectrometry Laboratory, Target Discovery Institute

Karl Morten, Nuffield department of Women’s and reproductive health 

Jan Lindeman, Leiden University Medical Center

My research focuses on investigating molecular mechanisms of tissue injury and repair in organ donation and transplantation. This is important as it will lead to better understanding of the type of injury organs are subjected to upon brain death (DBD) and circulatory death (DCD) and ultimately may help improve their quality and longevity, once transplanted.

My main research interest is in oxidative stress, mitochondrial signalling, bioenergetics and mitochondrial dynamics in health and disease and in organ transplantation. I am interested in applying biomolecular and –omics techniques to identify mechanisms of tissue injury in liver, kidney and pancreas and discover potential therapeutic targets for organ repair. In my research so far, I have investigated nitric oxide (˙NO) and hydrogen sulfide (H₂S) chemical biology, including their cytoprotective properties, and mitochondrial function and dysfunction in ischaemia-reperfusion (I/R) injury models, patients with mitochondrial diseases and deceased donor organs. I have focussed on mitochondrial function by studying ROS production, mitochondrial bioenergetics and autophagy/mitophagy pathways. I am also interested in studying the effects of ischaemia-reperfusion injury in abdominal organs, mainly by looking at protein expression and gene ontology/pathway analysis.

Thanks to the use of samples collected as part of the QUOD biobank and COPE trials, I have been able to investigate pathways of injury and repair in DBD and DCD donor kidneys and livers, including more marginal organs or donors with acute kidney injury. I have also been able to study how different preservation strategies (e.g. hypothermic and normothermic machine perfusion) change the organ proteome profile. 

Understanding the injury to donor organs and identifying targets for repair will help improve current protocols for the management of donors and organ preservation techniques (such as machine perfusion), with a view at eventually increasing transplant numbers and their longevity.