Le PerMedCoE, centre d’excellence HPC/Exascale pour la médecine personnalisée en Europe,. à organise un webinaire qui a pour thème :
« Development of a virtual Rheumatoid Arthritis synovial fibroblast for large-scale dynamic analysis and efficient drug-target identification »
Intervenant : Dr Anna Niarakis
Laboratoire Genhotel – Université d’Evry Val d’Essonne & INRIA
Abstract :Rheumatoid arthritis (RA) is a complex, systemic autoimmune disease that primarily affects the lining of the synovial joints and involves an intricate interplay among genotype and environmental triggers. Early RA starts with the infiltration of the synovial compartment by leukocytes. Then, the synovial fluid is inundated with pro-inflammatory mediators inducing an inflammatory cascade characterised by fibroblast-like synoviocytes (FLS) interactions with cells of the innate and adaptive immune system. Cytokines are key mediators, whereas drugs inhibiting these cytokines lead to RA therapies. Unfortunately, 40% of patients fail to respond to therapy.
Recently, many studies have shown that RA FLS activation and the subsequent joint damage they perpetuate are associated with an altered metabolism that may be therapeutically targetable.
Thus, RA FLS-directed therapies could become a complementary approach to immune-directed therapies.
She will present our efforts to construct a virtual RA FLS and develop a computational method to simulate large-scale coupled logical and metabolic models using Boolean and constraint-based modelling. The digital RA FLS can be used to predict intervention points for minimising the sustained inflammation, bone erosion, and cartilage destruction and identify druggable metabolic switches that could help us reprogram these cells to acquire an anti-inflammatory phenotype.