Research Group Bojana Müller-Durovic, PD Dr. med

Rheumatoid arthritis (RA) is the most prevalent form of inflammatory arthritis. Tryptophan metabolism is regulated by inflammatory cues through induction of indoleamine 2,3-dioxygenase 1 (IDO1), which directs tryptophan into the kynurenine pathway, accumulating downstream metabolites. In monocytes from RA patients, we observe spontaneous upregulation of tryptophan metabolism toward the kynurenine pathway. In this project, we seek to uncover the cell-intrinsic function of these metabolites using metabolomics, istopoe tracer studies, multi-omics data analysis and validation in in vitro and in vivo models as well as translational studies with the goal to better understand how this pathway regulates macrophage function in RA.

Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are autoimmune diseases marked by inflammation in the joints and/or skin. However, the early events leading to the full development of these conditions remain poorly understood. This study aims to uncover and characterize immunometabolic changes in immune cells, particularly in monocytes and T cells from peripheral blood and tissue biopsies, from these patients. To achieve this, we will employ untargeted metabolomics, transcriptome, and single-cell transcriptome analysis, and integrated bioinformatics approaches. The goal is to gain a better understanding of the metabolic changes occurring as these diseases progress, with a specific focus on the preclinical phase of RA and the transition from skin to joint involvement in PsA.

Sjogren’s Disease is a complex autoimmune disorder primarily affecting exocrine glands, leading to dryness and systemic inflammation. The disease spectrum extends beyond these symptoms, encompassing significant inflammation and tissue destruction as well as an increased risk of lymphoma. This project aims to comprehensively investigate metabolic programs of immune cells in Sjogren’s Disease. By combining single-cell RNA sequencing and metabolomics from salivary gland biopsies and peripheral blood of Sjögren’s patients and control patients with Sicca syndrome, we aim to delineate the metabolic processes that drive local inflammation, systemic autoimmunity, and lymphoma development in these patients.

As a side project, we will explore metabolic changes in the nationwide French cohort, Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS cohort), as well as the Paris-Saclay cohort, in collaboration with Prof. Xavier Mariette.