I am trained as an organic/medicinal chemist and nowadays take advantage of chemistry in combination with chemical biology techniques to interrogate the complex ubiquitin proteasome system. Post-translational modification of proteins with ubiquitin (Ub) is a dynamic process that regulates a breath of biological processes, including protein homeostasis, signalling and DNA repair. A cascade of E1, E2, E3 enzymes is responsible for the defined conjugation of a Ub to a substrate, whereas removal of the Ub is regulated by proteases termed deubiquitylating enzymes (DUBs). I developed a novel ABP to study substrate context in the monitoring of DUB activity, the first ligase probe that can travel and trap the full conjugation machinery and more recently ABPs based on ubiquitin-like proteins. Currently, I am working on methods to dissect the role of the Ubiquitin Proteasome System (UPS) in Huntington’s Disease.
I completed my PhD at the division Medicinal Chemistry at the University of Utrecht studying the design and synthesis of a novel class of macrocyclic antifungal peptides, echinocandins, which inhibit the b-(1,3)-D-glucan synthase complex, absent in mammalian cells. I then joined as a postdoc in the group of Prof. Dr. Huib Ovaa where my research focusses on chemical biology research in the Ubiquitin Proteasome Field. I was awarded in 2018 with a ZonMw OffRoad grant to study the UPS in Huntington’s Disease.
A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes.
Mulder MPC, Witting K, Berlin I, Pruneda JN, Wu KP, Chang JG, Merkx R, Bialas J, Groettrup M, Vertegaal AC, Schulman BA, Komander D, Neefjes J, El Oualid F, Ovaa H.
Nat Chem Biol. 2016 Jul;12(7):523-30.
Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne.
Mevissen TET, Kulathu Y*, Mulder MPC*, Geurink PP, Maslen SL, Gersch M, Elliott PR, Burke JE, van Tol BDM, Akutsu M, Oualid FE, Kawasaki M, Freund SMV, Ovaa H, Komander D.
Nature. 2016 Oct 20;538(7625):402-405.
Total Chemical Synthesis of SUMO and SUMO-Based Probes for Profiling the Activity of SUMO-Specific Proteases.
Mulder MPCǂ, Merkx R, Witting KF, Hameed DS, El Atmioui D, Lelieveld L, Liebelt F, Neefjes J, Berlin I, Vertegaal ACO, Ovaa Hǂ.
Angew Chem Int Ed Engl. 2018 Jul 16;57(29):8958-8962.