Systems Medicine – a holistic approach to promoting healthy ageing

The Systems Medicine Group has comprehensive experience in molecular epidemiology and systems medicine research, with a focus on investigating complex common diseases, which are strongly driven by the ageing process. Our research themes range from cardiovascular diseases, such as thrombotic disease and heart failure, to cardiometabolic conditions like obesity and type 2 diabetes mellitus, as well as infectious diseases with system-wide sequelae (SARS-CoV-2 and COVID-19) and cancers. The study of how the ageing process induces pathological changes is highly clinically relevant and a key priority for our group.
By using artificial intelligence (AI) methods and state-of-the-art high-throughput omics profiling techniques, we holistically integrate multi-omics data with environmental exposures, (sub)clinical parameters and advanced imaging data to discover new biomarkers and biosignatures, detect diseases at an earlier stage and predict their further progression. This serves as the basis for developing tailor-made therapies, diagnostics, prognostics and therapy-monitoring tools that best suit a patient’s response to therapy. A key strength of our group is our large multidisciplinary team, spanning expertise from molecular biology, biomedicine and clinical and molecular epidemiology to bioinformatics, biostatistics/AI and disciplines critical for maintaining a large clinical research infrastructure (e.g. IT, biobanking, regulatory affairs).

Exemplary highlights
One rapidly growing research area is clinical epigenetics. In the EpiHF project (collaborators: Prof. Christoph Niehrs [IMB] and Prof. Steve Horvath [Altos labs]), which is a ReALity/SHARP network collaboration, we investigate the role of DNA methylation as a readout of environmental exposure for the development and progression of heart failure. We do this by analysing global (whole genome), regional (gene region-specific) and specific methylation (epigenome-wide association studies, EWAS). The recent expansion of the clinical epigenetics unit and its resources (MethylationEPIC 850k array analysis of more than 5,000 individuals, as well as sequential sampling) now puts it among the top 5 largest cohorts in the world for analysing DNA methylation in cardiovascular disease.
In the area of thrombotic disease, our team initiated a multinational GWAS consortium to discover additional genetic loci implicated in hypercoagulability. Our latest success in the area of thrombotic disease is our leading participation in the trail-blazing excellence cluster curATime (curatime.org; funding volume for the first 3 years: €15m), in which we collaborate with basic researchers, drug developers (TRON, BioNTech), as well as several large and small-to-medium enterprises, to identify and evaluate new therapeutic targets for atherothrombosis and convert these into actionable interventions using innovative RNA-based immunotherapy.