Nitric oxide/redox signalling in health and disease (e.g., myocardial ischaemia, diabetes, heart failure and atrial fibrillation)
Our group is funded by a Programme Grant of the British Heart Foundation
Group members Ricardo Carnicer, PhD Postdoctoral scientist (BHF); Raja Jayaram, Clinical Research Fellow (BRC); Xing Liu, PhD Postdoctoral scientist (MRC); Svetlana Reilly, DPhil student (Clarendon Trust & Queen’s College); Xiaohui Sun, PhD Postdoctoral scientist (Garfield Weston Trust); Radu Tanacli, DPhil student (BHF); Mei Hua Zhang, PhD Senior postdoctoral scientist (BHF);
Our programme of work aims to understand nitric oxide (NO) and redox signalling in the healthy and diseased myocardium and explore the hypothesis that targeting relevant sources of NO and reactive oxygen species may open new therapeutic avenues for cardiovascular disease.
This focus has underpinned a longstanding collaboration with Prof Keith Channon based on our common interest in NO-redox biology and complementary expertise. Our joint work has contributed to the award of a Fondation Leducq Transatlantic Network of Excellence on “Redox and Nitrosative Regulation of Cardiac Remodeling: Novel Therapeutic Approaches for Heart Failure”.
As part of an EU consortium of investigators with a common interest in atrial fibrillation (EUTRAF http://www.eutraf.eu) we undertake preclinical studies using small molecules or gene transfer in large animal models of human disease, enabling crucial intermediate steps in the path leading to clinical translation of basic findings.
In addition, in collaboration with the University of Maastricht, we have developed techniques for evaluating the cardiac electrophysiological phenotype of murine models of human disease (e.g., in vivo programmed electrical stimulation and optical mapping in isolated hearts). In silico modelling in the context of human atrial fibrillation has also being developed in collaboration with Dr Blanca Rodriguez (Department of Computer Science, Oxford) and used as an hypothesis-generating tool to dissect the ion channels and transporters involved in the changes in action potential duration and calcium handling that are evoked by the activity of oxidase systems in atrial myocytes isolated from patients with atrial fibrillation.
In parallel with investigations in human cardiac tissue and animal models, we have a strong focus on patient-based research comprising mechanistic in vivo and in vitro studies, prospective investigations in cohorts of patients and, more recently, clinical trials. In this respect, our research has been directed to the identification of biomarkers and therapeutic targets for the prediction and prevention of atrial fibrillation and other in-hospital complications in patients undergoing cardiac surgery and to studies of the role of NO released by the neuronal isoform of NO synthase in the regulation of vascular tone and arterial blood pressure in humans in vivo. Mechanistic patient-based investigations and a large outcome trial currently recruiting at the Department of Cardiothoracic Surgery of the Fuwai Hospital in Beijing involve collaboration with Prof Zhengming Chen and Prof Rory Collins in the Clinical Trial Service Unit of the University of Oxford. This work is funded by a British Heart Foundation Programme Grant and Chair to Prof Casadei.
We use an integrative approach linking basic science to clinical investigations. This has proved to be an efficient way of testing hypotheses and has provided a stimulating training environment for both medical and science graduates.
Several trainees in our group have been awarded prestigious prizes/fellowships (e.g., Dr Claire Sears, Dorothy Hodgkin Fellow of the Royal Society, was awarded the Melvin L. Marcus Young Investigator Award of the American Heart Association in 2002).
We are keen to recruit talented and enthusiastic researchers with an interest in heart failure or atrial fibrillation.
We have established successful collaborations with several colleagues in the Department of Cardiovascular Medicine (e.g., Professor Stefan Neubauer, Professor Keith Channon, Prof. Hugh Watkins, Dr Nicholas Alp, Dr Craig Lygate and Dr Charles Redwood) and with Prof. Ulrich Schotten in Maastricht.