Saskia Nijmeijer wins Dutch Pharmacological Society thesis prize
Medicinal chemist Saskia Nijmeijer has been awarded the triennial thesis prize (€1500) of the Dutch Pharmacological Society (NVF) for her thesis Pharmacological characterization of novel histamine H4 receptor ligands.
The prize was given to Nijmeijer during the NVF Spring meeting April 24th in Nijmegen. Nijmeijer, postdoc in the Division of Medicinal Chemistry and AIMMS received her PhD degree in 2013 on her study of the G protein-coupled receptor (GPCR) histamine H4, under supervision of Dr Henry Vischer and Prof. Rob Leurs.
Biased receptor ligands
GPCRs activate multiple pathways in response to their natural ligands. Biased GPCR ligands activate only a subset of these pathways and could therefore function as improved medicines with less side-effects compared to conventional drugs. Preferably, biased drugs would only target the dysregulated (pathological) pathway and do not affect normal (beneficial) signalling pathways. Knowledge on the molecular mechanisms that are responsible for biased ligand binding and signalling will help to specifically design biased GPCR ligands and understand the physiological relevance.
An important part of Nijmeijer her research focused on biased GPCR ligands. She investigated whether ligands that bind to the histamine H4 receptor are able to induce a biased signal. Both G-protein and β-arrestin-biased ligands were found, which will function as interesting tool compounds to further unravel biased H4R signalling. Another topic involved the use of fragment-based drug discovery (FBDD) to study biased signalling. Small molecules (fragments) are useful to investigate regions in the GPCR binding pocket that are responsible for biased signalling (i.e. G protein or β-arrestin).
Current research focus
In 2014 Nijmeijer, winner of several (inter)national scientific presentation prizes, received a NWO Veni grant from the Netherlands Organization for Scientific Research to start a new research line on the role of adhesion G protein-coupled receptors in glioblastoma – the most common and most aggressive brain tumour. A better understanding of the biochemical functioning of these receptors could form the starting point for novel therapeutics.