Meet Our Research Team
Real people. Real science. Real enthusiasm.
Jörg Distler, Univ. -Prof. Dr. med.
Director Hiller Research Center and
Dept. of Rheumatology, University Hospital Düsseldorf
Spatial Biology of Heart and Muscle Involvement in Autoimmune Connective Tissue Diseases Team
Our research group focuses on systemic sclerosis (SSc), a complex systemic rheumatic disease that, despite major scientific advances in recent years, still carries the highest disease-related mortality in rheumatology. A second major pillar of our work is immune-mediated inflammatory myopathies (IIM), a diverse group of rare systemic disorders characterized by muscle weakness and, in many patients, involvement of other organs such as the skin and lungs. To better understand the cellular and molecular mechanisms driving SSc and IIM, we apply state-of-the-art spatial multi-omics technologies. These approaches allow us to dissect disease processes at unprecedented resolution and to identify novel therapeutic targets for future treatments. An equally important goal of our group is the implementation of precision-medicine strategies to improve risk stratification, treatment decisions, and ultimately the prognosis of patients with heterogeneous rheumatic diseases—particularly SSc and IIM.
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Spatial Biology and Multiplex Imaging Team
Advances in technology are rapidly transforming the field of biomedical research. Spatial biology techniques have garnered significant attention, with several being recognized as “Method of the Year” in 2020 and 2024. These methods provide high-throughput data that integrates spatial information about tissue architecture.
Our team is dedicated to unraveling the aberrant cellular organization within tissues affected by inflammatory and fibrotic diseases. We employ cutting-edge spatial biology methodologies, including highly multiplexed protein imaging such as imaging mass cytometry and cyclic in situ hybridization.
To extract meaningful biological insights from the huge amounts of data these techniques generate, we integrate state-of-the-art bioinformatics tools into our analyses. For instance, in one project, we explored the spatial distribution of fibroblasts and their cellular niches within systemic sclerosis skin tissues. This study also revealed cellular interactions associated with disease progression. Our ultimate goal is to leverage these insights to drive the development of effective therapies.
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Immune-Stromal Interactions in Autoimmune Diseases Team
Autoimmune diseases are characterized by the aberrant and sustained activation of immune cells within affected tissues and organs. In our laboratory, we employ cutting-edge technologies such as Imaging CyTOF (IMC) and in situ RNA sequencing to resolve the spatial organization and complex interactions between immune and tissue-resident cells in patient samples at high resolution.
Building on these data, we develop a dynamic 3D organ-on-chip platform that enables us to investigate the formation, organization, and persistence of pathological immune niches in a fully human model system.
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3D Disease Modeling and Tissue Engineering Team
The primary focus of my group is the development of advanced organotypic model systems to study the interplay between fibrotic, vascular, and autoimmune processes in systemic sclerosis and other inflammatory rheumatic diseases. These human organ models more faithfully recapitulate disease initiation and progression than conventional experimental systems and provide improved predictive power for therapeutic responses in patients.
In parallel, we aim to systematically characterize cell–cell interactions and aberrant signaling pathways in inflammatory rheumatic diseases using multi-omics approaches, with a particular emphasis on spatial proteomics and transcriptomics. These technologies enable us not only to quantify disease-associated changes in cell populations, but also to resolve disease-specific spatial remodeling between mesenchymal cells, immune cells, and the vascular niche.
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Synovial Immunology and Arthritis Team
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease affecting about 1% of adults. Reactive oxygen species promote RA by inducing endoplasmic reticulum stress, enhancing pro-inflammatory cytokines, and fostering autoimmunity. Tumor necrosis factor (TNF), a central driver of RA pathology, upregulates the calcium-permeable ion channel TRPA1 in fibroblast-like synoviocytes (FLS). TRPA1, in turn, activates calcium-sensitive pathways such as autophagy and apoptosis and is negatively regulated by the antioxidant transcription factor Nrf2, which restrains TNF-driven inflammation. We found that TRPA1 is elevated in TNF-stimulated FLS and that its activation by ligands including cannabinoids, such as tetrahydrocannabinol and cannabigerol, induces FLS death, suggesting TRPA1 as a promising therapeutic target. In a current project, we map TRPA1 expression across FLS subsets and immune cells in synovial tissue, define Nrf2-dependent regulation of TRPA1 and its signaling, dissect TRPA1-controlled downstream pathways and mediators and test the impact of TRPA1 agonism and antagonism in hTNFtg and collagen-induced arthritis mouse models. We use state-of-the-art technologies including imaging mass cytometry, RNA sequencing, CRISPR editing, siRNA, advanced 3D cultures, and multiparameter flow cytometry to uncover TRPA1-centered pathways as novel intervention points in RA.
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Transcription Factors and Cell Fate in the Pathogphysiology of Fibrotic Tissue Remodeling Team
Fibrosis is the defining pathological hallmark of systemic sclerosis (SSc). Fibrotic tissue remodeling represents a major burden to modern societies and is estimated to account for up to 45% of deaths in industrialized countries, underscoring the urgent need for effective disease-modifying therapies. My research focuses on the molecular mechanisms driving the pathogenesis of fibrotic diseases.
By selectively inactivating key target proteins and signaling pathways during the differentiation of fibroblasts into myofibroblasts, and by employing multiple in vivo models of SSc, we use classical molecular biology techniques together with multi-omics approaches such as RNA sequencing, imaging mass cytometry to dissect the regulatory roles of morphogen pathways, nuclear receptors, transcription factors and cell fate in systemic sclerosis.
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Immunometabolic Crosstalk in Systemic Sclerosis Team
Our group investigates how metabolic reprogramming shapes fibroblast-immune cell interactions in Systemic sclerosis (SSc), a complex autoimmune disorder marked by chronic inflammation and progressive fibrosis.
We aim to define how altered metabolism drives fibroblast activation and immune dysregulation by integrating single-cell genomics, metabolomics and functional assays. Using co-culture systems, gene editing and metabolic flux analysis, we identify key metabolic regulators and elucidate the mechanisms governing fibroblast-immune crosstalk. Our goal is to identify metabolic targets that regulate fibrosis progression and restore immune homeostasis in SSc.
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Experimental-Translational Mechanisms of Fibrotic Remodeling in Systemic Sclerosis Team
Systemic sclerosis (SSc) is a severe autoimmune disease characterized by widespread fibrosis, vascular damage, and immune dysregulation, making it the rheumatic condition with the highest mortality rate. This life-threatening fibrosis progressively damage vital organs like lungs, heart, and skin through relentless fibrous deposition, with limited treatments that merely slow progression rather than cure or halt it. Our team aims to uncover disease mechanisms through rigorous investigation, translating these insights into novel therapies that could efficiently stop SSc progression.
We actively screen novel therapeutic targets using unbiased omics approaches (eg. Bulk RNAseq, Imaging Cytof, OLINKs, or single-cell RNA sequencing), leveraging internal datasets, public databases, and patient-derived samples. Mechanisms are then dissected across translational models including in vitro cell systems, in vivo mouse models (like bleomycin- or topoisomerase- or chronic graft-versus-host disease induced fibrosis), ex vivo human precision-cut slices and organoids, plus multiple engineered remodeling platforms. Our efforts culminate in creating targeted therapies aligned with these specific mechanisms of action.
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Molecular Regulation of Stromal and T Cell Responses in Fibrotic Diseases Team
Our research group investigates the cellular and molecular mechanisms that drive fibrosis and immune dysregulation in systemic sclerosis and related diseases. We are particularly interested in understanding how fibroblast activation, T cell heterogeneity, and immune-stromal crosstalk contribute to chronic tissue remodeling and disease progression.
To address these questions, we combine mechanistic studies in primary cells with transcriptomic, molecular, and imaging-based approaches, as well as clinically relevant ex vivo and in vivo models. By profiling disease-relevant stromal and immune cell populations in affected tissues, we aim to identify pathogenic pathways and functionally distinct cell subsets that may serve as therapeutic targets.
Through the integration of basic and translational research, our goal is to advance the understanding of fibrotic disease pathogenesis and to support the development of mechanism-based treatment strategies for systemic sclerosis and related fibrotic disorders.