Research interests
Targeting the undruggable proteome
Over 80% of human proteins, including many important cancer drivers, cannot be targeted with conventional drugs (such as enzyme inhibitors) - we therefore clearly need novel approaches to tackle these target proteins and their associated disorders.
I have a particular interest in a novel strategy called targeted protein degradation, an approach that allows us to degrade a problematic protein using chemical compounds, so-called degraders, that hijack the cell's own waste disposal system.
Molecular glue degraders
The compounds I study, called molecular glue degraders, effectively glue together a target protein to a ubiquitin ligase, an enzyme that marks proteins for proteosomal degradation. This ultimately leads to the destruction of the disease-causing target by the cell. Drugs such as lenalidomide (Revlimid), which were only retrospectively found to function through this unusual mechanism, have revolutionised the treatment of several blood cancers and currently top the charts of highest revenue-generating drugs. However, such drugs have been found mostly serendipitously so far. My research therefore aims to enable the discovery, or even rational design, of glue compounds that will make effective therapeutics. For this, I work to identify more examples of molecular glue degraders and, through the visualisation of the "glued" complexes, understand how these compounds modulate protein-protein interfaces at the molecular level.
Degraders of cyclin K
My research aims to identify more examples of molecular glue degraders and through the visualisation of the "glued" complexes understand how these compounds modulate protein-protein interfaces at the molecular level. My recent publications explore different methodologies to prospectively discover molecular glue degraders and describe the discovery of novel, unusual glues that degrade the protein cyclin K.
Targeting transcription factors
Aside from my main PhD project, I contributed to several studies that explore how transcription factors (and other DNA-binding proteins), interact with DNA and other cofactors in the context of chromatin. This led me to develop an avid interest in the therapeutic targeting of transcription factors, the canonical undruggable targets, using targeted protein degradation and other induced proximity approaches.
