Joel began his scientific career with a three-year apprenticeship in medicinal chemistry at Roche Basel, followed by a Bachelor's in Molecular Life Sciences (Muttenz, Switzerland) and a Master's in Chemistry (Leiden, Netherlands). He completed his PhD in the Molecular Physiology group at Leiden University under Prof. Mario van der Stelt, developing a chemical proteomics platform ‘CellEKT’ to profile kinase inhibitors. Joel now continues this work as a Postdoc in a collaboration between Leiden University and Roche.

Abstract: To prevent unforeseen side effects of kinase drug candidates, efficient methods for determining target engagement across the cellular kinome are essential. We addressed this need by implementing the CellEKT (Cellular Endogenous Kinase Targeting)1 chemical proteomics platform, based on the broad-spectrum kinase probe XO44.2,3 This platform enables profiling of both covalent and non-covalent inhibitors across 304 kinases in human cells. To further expand kinome coverage, we developed an in silico pipeline to identify highly promiscuous kinase inhibitor scaffolds suitable for modification with lysine-targeting warheads. This approach led to the design, synthesis, and characterization of 24 novel broad-spectrum kinase probes. Combined, these probes cover over 90% of the expressed kinome in HEK293T and MV4-11 cells, as demonstrated using a data-independent acquisition (DIA) proteomics workflow. These advances significantly enhance the performance of the CellEKT platform, offering unprecedented depth in profiling kinase inhibitor engagement in living systems—a critical step toward improving the safety and efficacy of kinase-targeted therapies.
References: 1) Rüegger, J. et al. CellEKT: A robust chemical proteomics workflow to profile cellular target engagement of kinase inhibitors. Mol. Cell. Proteom. 100961 (2025).2) Zhao, Q. et al. Broad-Spectrum Kinase Profiling in Live Cells with Lysine-Targeted Sulfonyl Fluoride Probes. Journal of the American Chemical Society 139, 680–685 (2017).3) Yang, T. et al. Reversible lysine-targeted probes reveal residence time-based kinase selectivity. Nat Chem Biol 1–8 (2022).