Carbohydrates play key roles in a wide variety of cellular processes. When attached to proteins, they can, for example, regulate protein stability and mediate cell-cell and cell-pathogen interactions. These glycoconjugates are often extended into complex, branched carbohydrate structures. The exact structures of the various glycoconjugates are determined by the enzymes that are responsible for building up, remodeling and breaking down carbohydrate chains. Defects in several of these enzymes, as well as in the glycoconjugates themselves, have been found to be at the basis of various human diseases.
My research is focused on the development of chemical tools to study fundamental processes in glycobiology. By using a multidisciplinary approach, spanning the disciplines of organic chemistry, biochemistry, cell and molecular biology, we can study the cellular roles of carbohydrates and carbohydrate-processing enzymes. With this information, we aim to gain a better understanding of the molecular mechanisms behind their functioning, their impact on cellular physiology and how defects lead to human disease. Current interests include:
Lianne Willems received her PhD from Leiden University, The Netherlands in 2014, working with Prof Overkleeft on the topic of developing novel strategies for activity-based profiling of glycosidases and proteases. She then went on to postdoctoral research at Simon Fraser University in Canada in the laboratory of Prof Vocadlo. For her research on bioorthogonal chemistry approaches for functional analysis of co-translational O-glycosylation, she received a Banting Postdoctoral Fellowship from the Natural Sciences and Engineering Research Council (NSERC) in Canada, as well as a Rubicon fellowship from the Netherlands Organisation of Scientific Research (NWO).
Tan, H.Y.; Eskandari, R.; Shen, D.; Zhu, Y.; Liu, T.-W.; Willems, L.I.; Alteen, M.G.; Madden, Z.; Vocadlo, D.J. Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates. J. Am. Chem. Soc. 2018, 140 (45), 15300-15308.
Roth, C.; Chan, S.; Offen, W. A.; Hemsworth, G. R.; Hubbard, R. E.; Willems, L. I.; King, D. T.; Varghese, V.; Britton, R.; Vocadlo, D. J.; Davies, G. J. Structural and functional insight into human O-GlcNAcase. Nat. Chem. Biol. 2017, 13 (6), 610-612.
Willems, L. I.; Marques, A. R. (co-first author); Herrera Moro, D.; Florea, B. I.; Scheij, S.; Ottenhoff, R.; Van Roomen, C.; Verhoek, M.; Nelson, J. K.; Kallemeijn, W. W.; Biela-Banas, A.; Martin, O. R.; Cachón-González, M. B.; Kim, N. N.; Cox, T. M.; Boot, R. G.; Overkleeft, H. S.; Aerts, J. M. A specific activity-based probe to monitor family GH59 galactosylceramidase - the enzyme deficient in Krabbe disease. Chembiochem 2017, 18 (4), 402-412.
Willems, L. I.; Murray, B.; Beenakker, T. J.; Scheij, S.; Kallemeijn, W. W.; Boot, R. G.; Verhoek, M.; Donker-Koopman, W. E.; Ferraz, M. J.; van Rijssel, E. R.; Florea, B. I.; Codée, J. D.; van der Marel, G. A.; Aerts, J. M.; Overkleeft, H. S. Potent and selective activity-based probes for GH27 human retaining α-galactosidases, J. Am. Chem. Soc. 2014, 136, 11622-11625.
Willems, L. I.; Beenakker, T. J. M.; Murray, B.; Gagestein, B.; van den Elst, H.; van Rijssel, E. R.; Codée, J. D. C.; Kallemeijn, W. W.; Aerts, J. M. F. G.; van der Marel, G. A.; Overkleeft, H. S. Synthesis of α- and β-galactopyranose-configured isomers of cyclophellitol and cyclophellitol aziridine, Eur. J. Org. Chem. 2014, 2014, 6044-6056.
Willems, L. I.; Li, N.; Florea, B. I.; Ruben, M.; van der Marel, G. A.; Overkleeft, H. S. Triple bioorthogonal ligation strategy for simultaneous labeling of multiple enzymatic activities, Angew. Chem. Int. Ed. 2012, 51, 4431-4434.
Willems, L. I.; van der Linden, W. A.; Li, N.; Li, K.-Y.; Liu, N.; Hoogendoorn, S.; van der Marel, G. A.; Florea, B. I.; Overkleeft, H. S. Bioorthogonal chemistry: applications in activity-based protein profiling, Acc. Chem. Res. 2011, 44, 718-729.