My group studies enzymatic action in the ubiquitin proteasome system (UPS) and MHC class I antigen presentation using a combination of techniques including chemical synthesis and biochemistry. We are specialized in the design of assays and dedicated reagents that allow the study of protein ubiquitination and deubiquitination and that facilitate drug discovery efforts. We have an interest in the validation of potential therapeutic targets within the UPS with a focus on oncology while some are of relevance for the treatment of neurodegeneration. Approaches that the lab take include high-throughput screening using our acoustic dispensing system, hit validation and medicinal chemistry. Specific topics include modulation of the 26S proteasome activity (both activation and inhibition) in cells by small molecules as well as the development of dedicated PROTAC reagents. The lab is fully equipped for (high throughput) peptide synthesis, cell biology, biochemistry, immunology and high throughput small molecules screening, but also for medicinal chemistry. For details see www.ovaalab.nl. Next to screening and medicinal chemistry the lab has a longstanding interest in the development of probes that enable studies of the ubiquitin system. For example the lab has developed methods for the synthesis of ubiquitin and various ubiquitin-like reagents and probes.
I carried out my PhD in the laboratory of prof. Jacques van Boom and spent part of my PhD in the lab of prof. Blechert at the TU Berlin. I trained in the use of organometallic reactions on carbohydrate derived synthons to constract carbasugars. After my PhD I moved to the lab of prof. Hidde Ploegh at Harvard Medical School to get familiar with biochemistry and immunology. After two years as postdoc and then some time as instructor in pathology I moved to the Netherlands Cancer Institute in 2004 to start a lab with a focus on chemical biology, specializing in the chemistry of ubiquitination, proteasomal proteaolysis and antigen presentation. Since 2016 the lab is at Leiden Unverstity Medical Centre and part of the newly created department of Cell and Chemical Biology, where the lab has a focus on basic discovery, probe and assay development, and high throughput screening and medicinal chemistry.
My career was as follows:
2016 – present professor Leiden University Medical Centre
2016 – present professor Leiden University
2012 – 2015 extraordinary professor Leiden University
2010 – 2013 0.1FTE C.S.O. UbiQ Bio B.V.
2009 – 2016 Tenured staff member NKI
2005 – 2012 Assistant Professor, Leiden University, the Netherlands
2004 – 2009 Junior group leader, NKI
2004 – 2005 Guest Researcher, Leiden University
2003 – 2004 Instructor in Pathology, Harvard Medical School, Boston, USA
2001 – 2003 Post-doctoral fellow, Harvard Medical School, Boston, USA
ORCID ID: 0000-0002-0068-054X
On terminal alkynes that can react with active-site cysteine nucleophiles in proteases.
Ekkebus R, van Kasteren SI, Kulathu Y, Scholten A, Berlin I, Geurink PP, de Jong A, Goerdayal S, Neefjes J, Heck AJ, Komander D, Ovaa H.
J Am Chem Soc. 2013, 135(8), 2867-70
Chemical synthesis of ubiquitin, ubiquitin-based probes, and diubiquitin.
El Oualid F, Merkx R, Ekkebus R, Hameed DS, Smit JJ, de Jong A, Hilkmann H, Sixma TK, Ovaa H.
Angew Chem Int Ed Engl. 2010, 49(52):10149-53.
• Total Chemical Synthesis of SUMO and SUMO-Based Probes for Profiling the Activity of SUMO-Specific Proteases
Mulder MPC, Merkx R, Witting KF, Hameed DS, El Atmioui D, Lelieveld L, Liebelt F, Neefjes J, Berlin I, Vertegaal ACO, Ovaa H
Angew Chem Int Ed Engl. 2018, 57(29), 8958-8962.