Project Details
Projekt
Coordination Funds
Applicant
Professorin Dr. Gabriela Riemekasten
Subject Area
Rheumatology
Experimental Models for the Understanding of Nervous System Diseases
Cardiology, Angiology
Clinical Immunology and Allergology
Pneumology, Thoracic Surgery
Experimental Models for the Understanding of Nervous System Diseases
Cardiology, Angiology
Clinical Immunology and Allergology
Pneumology, Thoracic Surgery
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 552470287
Atherosclerotic vascular disease, ischemic stroke, and pulmonary arterial hypertension are severe vascular diseases (VDs) with substantial disease burden. These often-inflammatory conditions frequently arise as complications of systemic autoimmune diseases (ADs) and are major contributors to morbidity and mortality. Members of our planned consortium have identified a critical role for agonistic autoantibodies (Abs) targeting distinct G-protein coupled receptors (GPCRs) both as biomarkers and potential mediators of VDs. As endogenous modulators, GPCR Abs may shape inflammatory responses by influencing localization, intensity, and immune cell composition, acting as key regulators of vascular health and disease. We hypothesize that defined GPCR Abs exert disease-specific effects through cross-talk between immune and endothelial cells expressing relevant GPCRs. This interaction represents a novel concept for vascular inflammation. Our goal is to demonstrate that profiling these Abs and their target cells will yield crucial insights into pathogenic pathways in VDs. The present proposal seeks to elucidate the mechanisms underlying the pathogenicity of these Abs. We will focus on ADs, while also analysing non-autoimmune conditions to identify shared, disease-overarching pathways. Specifically, we aim to: i) delineate the molecular and cellular pathways that drive the emergence of pathogenic GPCR Abs and determine their quantities, ii) characterise and decipher the structural and functional properties of GPCR-Ab interactions including their downstream pathways, iii) evaluate the pathophysiological roles of specific GPCR Abs in animal models, and iv) modulate GPCR Abs or their downstream pathways in vascular disease models to identify novel checkpoints for interventions. Our interdisciplinary consortium of sixteen experts across ten disciplines is uniquely positioned to lead this research. We have pioneered investigations into agonistic GPCR Abs in VDs and are well equipped to bridge clinical and basic science in uncovering disease mechanisms. With access to well-characterized patient cohorts and custom-designed mouse models, we are positioned to study the full range of disease mechanisms. By combining cutting-edge methods - such as single-cell sequencing, high-resolution structural analyses, state-of-the-art imaging, deep immunophenotyping, and monoclonal antibody platforms, we will dissect antibody-mediated signaling and its downstream effects on cell function, tissue damage, and disease course. This project targets the complex biology and emergence of GPCR Abs, aiming to close the gap between basic research and clinical practice. By integrating insights from autoantibody biology and vascular pathology, we aim to uncover transformative mechanisms driving VDs and to develop predictive tools and innovative therapeutic strategies.
DFG Programme
Research Units
