Research interests
Chemical Biology: proteolysis, proteomics and antigen presentation.
The Ovaa group aims at the development of tools to profile cellular enzymatic activities associated primarily with ubiquitin and ubiquitin-like systems as well as proteasome activity, antigen production and -presentation and therapeutic intervention with individual components. The group uses an organic synthesis-driven approach to gain further understanding of biochemical processes. The approach chosen is pragmatic. We search for inhibitors of enzymatic activities both by screening en masse followed by hit-optimization and by rational design. We recently developed a chemical strategy to load MHC class I molecules on command. This strategy takes advantage of UV-cleavable peptides. Resulting peptide-receptive protein complexes, generated upon UV irradiation, can be readily loaded with an appropriate ligand.
Research is centered around one central theme: chemistry of protein degradation and antigen presentation, divided into three different topics:
Topic 1: Ubiquitin(-like) proteomics
Topic 2: Proteasome activity
Topic 3: Antigen presentation
The group has extensive experience in organic synthesis, expressed protein ligation, mass spectrometry, protein purification, and standard biochemical techniques.
Key publications
Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate. Misaghi, S.; Galardy, P.J.; Meester, W.J.; Ovaa, H.; Ploegh, H.L.; Gaudet, R. J. Biol. Chem. 2005, 1512-1520.
In vivo activity based drug profiling: additional proteasome subunits identified as targets of the anti-tumor agent bortezomib. Berkers, C.R.; Verdoes, M.; Lichtman, E.; Fiebiger, E.; Kessler, B.; Ploegh, H.L.; Ovaa, H.; Galardy, P.J. Nature Methods 2005 26(5), 252-257.
Immunotherapeutic potential for ceramide-based activators of iNKT cells. Berkers, C.R.; Ovaa H. Trends Pharmacol. Sci., 2005 26(5), 252-257.
Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2. Meulmeester, E.; Maurice, M. M.; Boutell, C.; Teunisse, A. F.; Ovaa, H.; Abraham, T.E.; Dirks, R.W.; Jochemsen, A.G. Mol Cell. 2005, 19(1),143-154
A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Chauhan, D.; Catley, L.; Li, G.; Podar, K.; Hideshima, T.; Velankar, M.; Mitsiades, C.; Mitsiades, N.; Yasui, H.; Letai, A.; Ovaa, H.; Berkers C.R.; Nicholson, B.; Chao, T.H.; Neuteboom, S.T.; Richardson, P.; Palladino, M.A.; Anderson, K.C. Cancer Cell. 2005, 8(5), 407-419.
Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome. Groll M, Berkers CR, Ploegh HL, Ovaa H. Structure. 2006, 14(3), 451-456.
Design and use of conditional MHC class I ligands. Toebes M, Coccoris M, Bins A, Rodenko B, Gomez R, Nieuwkoop NJ, van de Kasteele W, Rimmelzwaan GF, Haanen JB, Ovaa H, Schumacher TN. Nature Medicine. 2006, 12(2), 246-251.
Generation of peptide–MHC class I complexes through UV-mediated ligand exchange. Rodenko B, Toebes M, Reker Hadrup S, van Esch WJE, Molenaar AM, Schumacher TNM, Ovaa H. Nature Protocols, 1(3), 1120-1132.
Profiling Proteasome Activity in Tissue with Fluorescent Probes. Berkers CR, van Leeuwen FW, Groothuis TA, Peperzak V, van Tilburg EW, Borst J, Neefjes JJ, Ovaa H. Mol. Pharm. 2007, 5, 739-748.
Active-site directed probes to report enzymatic action in the ubiquitin proteasome system. H. Ovaa. Nature Rev. Cancer. 2007, 7(8), 613-20.
More publications by Huib Ovaa can be found on PubMed and additional chemistry articles can be found through ISI Thomson Web of Science.
List of relevant websites
Web of science homepage
Biographic sketch
Dr. Huib Ovaa (1973) received training in organic synthesis in the labs of the late Prof. Dr. J.H. van Boom (Leiden University) and Prof. Dr. S. Blechert (TU-Berlin) specializing in metathesis reactions on carbohydrate synthons. He received his Ph.D. in 2001, cum laude, at Leiden University, The Netherlands. After post-doctoral training in immunology in the lab of Prof. Dr. H.L. Ploegh at Harvard Medical School, he obtained a junior faculty position at Harvard. Since 2004 he is leading a research team specialized in organic synthesis, chemical biology and drug innovation at the Netherlands Cancer Institute specializing in the design and development of diagnostic and proteomic tools using a variety of approaches, including high-throughput small molecule screening with the ultimate goal of early diagnosis and treatment of cancer.
Co-workers
Celia Berkers MSc Graduate student
Boris Rodenko PhD Postdoctoral fellow
Silvia Cavalli MSc Postdoctoral fellow
Anitha Shanmugham PhD Postdoctoral fellow
Rieuwert Hoppes Graduate student
Harald Albers Graduate student
Henk Hilkmann ing Technician
Karianne Schuurman Technician
Annemieke de Jong Graduate student
Esther Bloem Graduate student
Jenny Vlug Graduate student
Positions available
We have a vacancy for a chemical proteomics project related to post-translational protein modification by the protein ubiquitin and by ubiquitin-like proteins. Click here for more information. We also have a vacancy for several undergraduate internships ('hoofdstage') with a minimal length of 9 months. For further information navigate to our website.
If you have a PhD degree in organic synthesis and if the following characteristics apply to you: enthousiastic, hard-working, team player and if you have an active interest in applying your knowledge to outstanding biomedical questions don’t hesitate to ask for more information about possibilities or fellowship options by emailing to Huib Ovaa.