Project Overview

Aim of the project

 

 The ArthritisHeal project aims to train young researchers to generate novel therapeutic targets in two rheumatic diseases: osteoarthritis (OA) and rheumatoid arthritis (RA). The therapeutic approach will be focused on the role of pro-resolving lipids, which play an important role in both diseases. By training early stage researchers (ESRs) in all aspects of (pre-)clinical research of complex diseases, they will be able to grow and become versatile researchers. Each ESR will have his/her own specialty, and interact with, and understand, researchers from other sectors and disciplines.

 

The challenge to address

Rheumatic diseases, such as RA and OA, cause pain and deformation of joints in ~10% of the population. Both diseases have an important inflammatory component, and, despite new therapeutic strategies including biologicals, neither disease can be cured. An exciting new opportunity to find a cure is to exploit and expand the evolving field of pro-resolving lipids, including the first-discovered classes of resolvins, protectins and maresins. Stimulating pro-resolving lipids, instead of blocking pro-inflammatory mediators, offers a novel way to treat rheumatic diseases. However, the complexity of this strategy requires collaboration of researchers from biology, chemistry and medicine.

 

The ArthritisHeal approach

The ArthritisHeal project combines research into the role of pro-resolving lipids in both OA and RA, which enables comparison of different aspects of inflammation in these diseases, as well as exploration of common mechanisms. The role of pro-resolving lipids will be examined in patient samples and in pre-clinical animal and in vitro models. First, pro-resolving lipids known to play an important role in inflammatory or auto-immune diseases will be studied in patient samples, and the mechanism of action investigated in corresponding pre-clinical models. Second, novel pro-resolving lipid pathways will be uncovered using untargeted lipidomics in self-resolving animal models, through state-of-the-art mass spectrometry (MS) methods. These novel mediators will also be correlated to clinical data and further studied in pre-clinical models, providing another important translational step between clinical and pre-clinical research.

 

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Work Packages in ArthritisHeal Project

 

The ArthritisHeal training network consists of four scientific WPs corresponding with the scientific objectives 1-4. Each of the 12 ESR projects will be positioned in one or more of WPs 1-4 having intense interaction according to the central interdisciplinary and translational training idea of ArthritisHeal. The common basis for all WPs is the epidemiologic and mechanistic evaluation of pro-resolving lipid pathways and functions in rheumatic diseases.

                                    

 

The interconnection of the WPs can be described as follows:

Known (e.g. from other inflammatory diseases) and novel pro-resolving lipids will be investigated in human patient cohorts at various stages of disease in WP1. Novel pro-resolving lipids will be fed into this WP from WP2, which is dedicated to discovery of novel pro-resolving mediators using untargeted lipidomics in animal models. The mechanism of action of the targets resulting from both these WPs will be evaluated in animal models of disease (WP3), whereas WP4 will assess the biological relevance of these pathways in human cells and tissues to investigate cellular and molecular mechanisms. This will add a deeper layer of translational research to the project.

Since the central idea of the ArthritisHeal project is the translational and multi-disciplinary training of ESRs, WP5 will be exclusively dedicated to training whereas WP6 will address dissemination and outreach of the project. Finally, WP7 will be fully dedicated to the management of the ArthritisHeal consortium.

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