Kinomics, a promising portal to deep understanding of cardiovascular disease and new druggable targets for intervention

• Applicant: Privatdozent Dr. Emiel van der Vorst
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569469700

All in all, it is clear that kinases play a crucial role in atherosclerosis and CVD. However, most kinases have not been investigated in this context, and their pathological role remains elusive. This project investigates the role of a newly identified CVD-relevant kinase NuaK1 in atherosclerosis by focusing on macrophages, one of the main cell types that are involved in atherogenesis and exploring its therapeutic potential. Based on preliminary studies, NuaK1 might have anti-inflammatory and atheroprotective effects. Furthermore, an unbiased kinomics approach will be deployed on human plaque macrophages in order to identify other novel CVD-relevant kinases, creating an interesting source of new leads to study in the future to ensure the continuity of my research group. Therefore, this project is subdivided into four main research objectives: In Objective 1, the exact role of NuaK1 in macrophages will be elucidated using various in-vitro approaches. In Objective 2, the effect of myeloid-specific NuaK1 on atherosclerosis development will be investigated in-vivo. In Objective 3, the therapeutic potential of NuaK1 will be investigated by in-vivo targeting of this kinase using lipid nanoparticles. In Objective 4, a kinome discovery approach will be performed by comparing human macrophages from low-risk and high-risk atherosclerotic plaques.

• DFG Programme: Research Grants