Health Protection Research Unit for Chemical & Radiation Threats & Hazards

Staff Profile

Professor David Jones

Professor of Liver Immunology

Background

I am NIHR Dean for Faculty Trainees and an active researcher in the area of Autoimmune Liver Disease, with a particular focus on the impact of the diseases on patients and how we can improve outcomes through the development and evaluation of new treatment approaches. I am the PI for the UK-PBC national research consortium (www.uk-pbc.com). Working with Newcastle colleagues I am the first Director for the Newcastle University Centre for Research Excellence in Rare Disease 

Research

My research interest was originally in the nature, antigen specificity, and mechanisms of control of T-cell response to autoantigens in the autoimmune liver disease primary biliary cirrhosis (now primary biliary cholangitis (PBC)). This has developed into a broader interest in mechanisms of T-cell control, and the potential role of mucosal immune-modulation in altering the nature of the immune response in terms of both vaccine development, and immunotherapy for autoimmune disease.

As the significance of the role played by target cells in autoimmune disease in terms of function loss and subsequent fibrosis development has come to be appreciated I developed a strand of research exploring mechanisms of biliary epithelial cell damage and loss. This work also has important implications for the development of novel treatments. Interest in the mechanisms underpinning autoimmune disease also led to an interest in the role played by genetic factors in disease pathogenesis and expression in PBC, initially in the context of candidate gene association and latterly in a Wellcome Trust funded GWAS programme which represented the largest single study performed worldwide in PBC to date. This work has evolved into a substantial programme of stratified medicine research in PBC (funded by the MRC) and more recently in autoimmune hepatitis (funded by the NIHR).   

My clinical research has been into aspects of the symptomatology, complications, therapy and outcomes in primary biliary cholangitis and other forms of autoimmune liver disease. I have a particular interest in the area of quality of life assessment in PBC, and the importance of development of QOL outcome measures for use in the assessment of novel therapies in PBC. This work has highlighted the importance of fatigue in the lives of PBC patients and has informed a novel experimental medicine programme exploring the mechanisms of fatigue using fMRI approaches allied to in vitro studies. This work, which has identified systemic bio-energetic abnormalities in PBC has contributed to a paradigm shift in our understanding of the nature and impact of this disease. This work has also shed important light on potential pathogenetic mechanisms for fatigue in other disease settings including chronic fatigue syndrome where I have an ongoing programme of work. I have significant experience as CI and PI in phase II and phase III clinical trials in PBC. I developed the leading PROM for use in PBC (the PBC-40) and have extensive experience of trial protocol development in PBC. This involvement culminated in my leading the team that got FDA approval for the first new therapy for PBC in 20 years, and the first ever stratified therapeutic agent in liver disease, in spring 2016. The stratified approach to the management of PBC has now been implemented into NHS practice. The trials programme has finally brought together the clinical and basic science aspects of my research. 

The UK-PBC consortium (www.UK-PBC.com) that I lead has been instrumental in increasing our understanding of the nature of risk in PBC and, crucially, leveraging that knowledge in innovative clinical trials using the UK-PBC patient cohort. 

Publications