Title: Genetics, omics, and AI phenotyping for drug target discovery in cardiovascular disease
Abstract: Cardiovascular drug development remains slow, costly, and marked by high attrition, highlighting the need for robust target prioritization frameworks. Human genetics anchors therapeutic hypotheses in causal biology through Mendelian randomization, colocalization, and phenome-wide analyses, enabling validation of target–indication pairs and early safety assessment. Genetically proxied perturbation of pathways such as IL6/IL6R signaling and the CCL2/CCR2 axis illustrates how inherited variation can inform cardiovascular risk reduction and repurposing opportunities. Integration of large-scale proteomics, single-cell transcriptomics, and plaque-level multi-omics allows mechanistic dissection of causal pathways and identification of downstream mediators. Coupling genomics with AI-driven deep phenotyping in large biobanks, including automated vascular imaging and arterial aging metrics, further enhances statistical power and biological resolution. Scalable integration of genetics, omics, and AI phenotyping offers a systematic strategy to bridge molecular variation to disease mechanisms and actionable drug targets in cardiovascular medicine.
Marios Georgakis is a research group leader and board-certified neurologist at the Institute for Stroke and Dementia Research, LMU Munich in Germany. He also serves as Visiting Scientist at the Broad Institute of MIT and Harvard. Dr. Georgakis trained in Medicine and Epidemiology at the University of Athens, before completing a PhD in Genetic Epidemiology and Neuroscience at LMU Munich. He pursued postdoctoral research at Harvard Medical School and the Broad Institute before returning to Munich as a research group leader in 2023.
His work sits at the interface of human genetics, molecular epidemiology, and vascular medicine. He is interested in the use of human genetic data to discover or validate targets for stroke and cardiovascular pathologies with a particular focus on inflammatory mechanisms driving atherosclerosis. Dr. Georgakis currently leads an interdisciplinary team integrating human genetics, multi-omics in human vascular tissue, and AI phenotyping in large-scale biobanks to identify actionable therapeutic targets and biomarkers for cardiovascular and cerebrovascular disease. His research is supported by the German Research Foundation (Emmy Noether Programme), the Hertie Foundation, the Fritz-Thyssen Foundation, and LMU Munich.
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