RNA metabolism and Vascular Inflammation
General scientific objectives:
Despite the current evidence-based guidelines on clinical practice of cardiovascular medicine, the clinical manifestations of atherosclerotic disease remain the major causes of morbidity and mortality. Atherosclerosis is a chronic nonresolving multifactorial vascular inflammatory disease with a pandemic and- till now- noncurable character. Identification of novel pathways that regulate inflammatory responses in microcirculation and microenvironment will enable us to understand the complex pathophysiology of vascular inflammation and to address novel therapeutic options. Our goal is to reveal the role of RNA modifications (e.g. RNA editing) and RNA-binding proteins in gene expression and organ function in inflammatory diseases. With the help of deep sequencing, molecular and cellular biology, genetics techniques and high-end molecular imaging, we identify in a single nucleotide resolution the regulatory networks that orchestrate an inflammatory response including neovascularization in vivo. Further, we aim to identify novel therapeutic candidates that modulate vascular and tissue inflammation by simultaneously targeting various genes and cell types. The relevance of our bench findings is further investigated in translational studies using animal disease models as well as in clinical studies involving patients with subclinical atherosclerosis, coronary heart disease, carotid atherosclerotic disease and aortic aneurysms.