Mario van der Stelt
Professor of Molecular physiology
There are still many life-threatening diseases, such as Alzheimer’s disease, metabolic syndrome and cancer, for which there are no suitable therapies available. Mario van der Stelt aims to discover new molecules that can act as drug candidates for these type of diseases.
My lab is recognized worldwide for the design, synthesis and application of small molecules as chemical tools to control and visualize proteins of the endocannabinoid system in physiological and disease processes. In multidisciplinary research lines organic and medicinal chemistry are combined with innovative chemical biology techniques, such as chemical proteomics, and gene editing to optimize and profile compounds as drug candidates. My current research interests are focused on the detection and modulation of endocannabinoid biosynthesis/metabolism and kinase signaling.
Recently, I have coordinated an (inter)national team that discovered the off-targets of the experimental drug BIA 10-2474, a fatty acid amide hydrolase inhibitor, which caused severe neurological symptoms and killed a patient in a first-into-human study in France (Science, 2017). I also led a multinational joint venture that reported an extensive cannabinoid CB2 receptor ligand profiling (Nature Commun, 2017; JACS, 2018).
Furthermore, my group discovered the first inhibitors of endocannabinoid biosynthesis in the brain (PNAS, 2016). Key to the discovery of these compounds was the development of tailored activity-based probes that could be used to determine the activity and selectivity of the compounds in complex brain proteomes using chemical proteomics (Nature Prot., 2018; JACS, 2015; ACS Chem. Biol., 2017; ACIE, 2013; J. Med. Chem., 2014, 2015, 2017). Previously, I was the first to report on the role of the endocannabinoid system in neurodegeneration and discovered that anandamide can act as an intracellular messenger (EMBO J. 2005; Science 2003; J. Neurosci, 2003, 2001a,b).