I am a chemical biologist at the Leiden University Medical Center (LUMC), Leiden, the Netherlands. I work at the interface between chemistry and cell biology to unravel the dynamic mechanisms of the multifaceted post-translational modification of substrate proteins by ubiquitin and ubiquitin-like proteins. This versatile signal regulating system, controlled by a complex enzymatic network, influences almost all aspects of normal cell biology and protein degradation. I specialize in the design of unique molecular tools that allow the study of protein (de)ubiquitination. The main emphasis of my research is to provide insights in protein ubiquitination and its dysregulation in disease, including new tools and methodology to translate this into therapeutic strategies.
I completed my PhD in medicinal chemistry at Utrecht University studying the design and synthesis of a novel class of macrocyclic antifungal peptides. I then moved to the Netherlands Cancer Institute and joined the group of the late Prof. Dr. Huib Ovaa as a postdoc where my research focused on the design of novel activity based probes to study enzymatic activity, using a chemical biology approach. This work, which continues to actively develop in my group at the LUMC, set the basis for our current studies on E3 ligases and the role of the ubiquitin proteasome system in Huntington’s disease. Although a therapy has still a long way to go, increasing selective turnover of the mutant huntingtin protein by selectively manipulating its ubiquitination represents an attractive therapeutic approach to prevent or delay onset and progression of this devastating disease.
Within the CureQ consortium, I will be working on WP4, aimed at the discovery of novel modulators of disease onset and progression. We will run a project (CureQ PhD student Christina Sutherland) on the (de)ubiquitinating enzymes involved in protein degradation of polyQ diseases.