Associated organisationsInstitute of Cancer Research · University of ManchesterEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£2.0M
PeriodAug 2018 — Oct 2023
In plain English
AI plain-English summary
This Centre of Excellence is using genetic markers to predict who will develop inflammatory arthritis, how their disease will progress, and which treatments will work best for them. The problem is that arthritis treatments today are largely trial-and-error. Patients often cycle through drugs that do not work for them, losing time and experiencing preventable joint damage. The researchers have already identified many genetic variants linked to arthritis susceptibility and outcomes. Now they need to understand exactly how those variants disrupt gene, protein, and cellular function to cause immune system dysregulation. If this work succeeds, it could transform how arthritis is managed. Instead of a one-size-fits-all approach, doctors could stratify patients by their genetic profile, personalise treatment from the start, and identify entirely new therapeutic targets. The pipeline for interpreting genome-wide association studies will also apply to other complex diseases beyond arthritis. The second programme is fundamental discovery science: understanding the precise mechanisms by which genetic variants cause arthritis. The researchers argue that such mechanistic understanding is essential if arthritis is ever to be cured or prevented. This is curiosity-driven work with no immediate clinical application, but similar fundamental genetics research has previously underpinned breakthroughs in cancer immunotherapy and targeted therapies for rare diseases.
View original technical description
We have established a Centre of Excellence in Genetics and Genomics of arthritic diseases with an international reputation for research identifying genetic markers of susceptibility to and outcomes of inflammatory arthritis and for training researchers of the future. We now plan to exploit that knowledge with two major programmes of research. In Translational Genetics we will translate the findings from susceptibility and outcome studies to prevent disease and it’s complications, predict treatment response and personalise treatment to the individual. In Functional Genomics, we will advance a programme of discovery science aimed at understanding exactly how genetic variants associated with inflammatory arthritis alter gene, protein and cellular function to cause dysregulation of the immune system; we believe that such a mechanistic understanding of arthritis causation is vital if we are ever to cure or prevent arthritis. By developing a pipeline to facilitate the interpretation of genome wide association studies, the impact of this programme, to inform patient stratification and personalised medicine and identify novel therapeutic targets, will reach beyond arthritis to other complex diseases. As a Centre of Excellence we will continue to deliver on currently funded research whilst leveraging new funding to support the proposed programmes. We will communicate our research findings in high impact scientific journals and to lay audiences, ensuring that clinical translation is prioritised. We will continue to collect samples for our research from our unique patient-based studies, supported by our recently established social enterprise company. We will maintain existing and build new collaborations nationally and internationally with academia and the commercial sector. Training of our own staff and students and visitors from other groups, to develop expertise in translational genetics, bioinformatics and functional genomics to establish the next generation of arthritis researchers, will remain a high priority.
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