Universiteit Leiden

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PhD defence

CellEKT: a chemical proteomics platform to study the kinome

  • J. Rüegger
Date
Friday 4 July 2025
Time
Location
Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

  • Prof.dr. M. van der Stelt
  • dr. A.P.A. Janssen
  • dr. R.J.B.H.N. van den Berg

Summary

Many promising medicines fail in clinical trials because they don’t work as expected or cause unwanted side effects. A major reason is that we often don’t fully understand how drugs interact with their targets in the complex environment of living cells. My PhD research set out to improve this by focusing on a specific group of proteins called kinases, which play central roles in diseases like cancer and are common drug targets.

To better study how kinase inhibitors work, we developed a chemical proteomics platform called CellEKT (Cellular Endogenous Kinase Targeting). This technique uses specially designed chemical probes that enter living cells and bind to kinases. Using advanced mass spectrometry and data analysis, we can then identify which kinases are affected by different drugs and how strongly.

One of the key achievements was expanding the platform’s reach. By designing new chemical probes, we were able to monitor over 90% of the kinases expressed in certain cancer cells. We also used CellEKT to study how cancer cells respond to treatments that induce senescence, a state where cells stop dividing. This revealed previously overlooked kinases that may help drive this process.

Overall, this research provides powerful new tools to understand how drugs act inside cells, improve their selectivity, and uncover how cells behave under treatment. These insights could help make future therapies safer and more effective—an important step toward tackling complex diseases like cancer.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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