Donders Institute for Brain, Cognition and Behaviour
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Theme 2: Perception, Action and Control

Glycosylation Disorders in Neurology

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Protein glycosylation is one of the few remaining unexplored fields in human medicine, as a third layer of biological information on top of genomics and proteomics. Even more than these established fields, the rich biological information contained in protein glycosylation offers unprecedented potential to identify patient-specific signatures, which will facilitate early diagnostics and therapy monitoring.

Our long term goal is to understand the mechanisms of protein- and tissue-specific glycosylation abnormalities in human disease with a focus on neurodegenerative and neuromuscular disease. Our findings are being translated into patient care via improved diagnostics and novel therapies, as successfully shown for a first neuromuscular disease

Contact
Name: Dirk Lefeber
Telephone: 024-309 3487
Email: Dirk.Lefeber@radboudumc.nl
Visiting address: Department of Neurology
Radboud University Nijmegen Medical Center / Route 774
Geert Grooteplein Zuid 10
6525 GA Nijmegen
The Netherlands
Postal address: Department of Neurology
Radboud University Nijmegen Medical Centre
P.O. Box 9101 / 830
6500 HB Nijmegen
The Netherlands
Key Grants & Prizes

“Metabolic manipulation as potential treatment for the dystroglycanopathies” Princess Beatrix Spierfonds for Neuromuscular research (2018)

“PGM1 deficiency- a heterogeneous myopathy with opportunities for treatment” Princess Beatrix Spierfonds for Neuromuscular research (2015)

“A sweet perspective in human medicine: Restoring protein glycosylation by modulating sugar supply pathways” Netherlands Scientific Organisation VIDI grant in medical sciences (2013)

Research award of the international society for inborn errors of metabolism (SSIEM) (2016)

VIDI Laureate in medical sciences of the Netherlands Organisation for Scientific Research (2013)

Research award of the international society for inborn errors of metabolism (SSIEM) (2010)

Key publications

Jansen EJ, Timal S, Ryan M, Ashikov A, van Scherpenzeel M, Graham LA, Mandel H, Hoischen A, Iancu TC, Raymond K, Steenbergen G, Gilissen C, Huijben K, van Bakel NH, Maeda Y, Rodenburg RJ, Adamowicz M, Crushell E, Koenen H, Adams D, Vodopiutz J, Greber-Platzer S, Müller T, Dueckers G, Morava E, Sykut-Cegielska J, Martens GJ, Wevers RA, Niehues T, Huynen MA, Veltman JA, Stevens TH, Lefeber DJ. ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation. Nature Communications. 2016;7:11600-11612.

Riemersma M, Froese DS, van Tol W, Engelke UF, Kopec J, van Scherpenzeel M, Ashikov A, Krojer T, von Delft F, Tessari M, Buczkowska A, Swiezewska E, Jae LT, Brummelkamp TR, Manya H, Endo T, van Bokhoven H, Yue WW, Lefeber DJ. Human ISPD Is a Cytidyltransferase Required for Dystroglycan O-Mannosylation. Chemistry & Biology 2015;22(12):1643-1652.

Tegtmeyer L*, Rust S*, Van Scherpenzeel M*, Ng B, Timal S, Raymond K, Losfeld M, He P, Ichikawa M, Veltman J, Huijben K, Shin Y, Sharma V, Adamowicz M, Lammens M, Reunert J, Witten A, Schrapers E, Matthijs G, Jaeken J, Rymen D, Stojkovic T, Stanley C, Matalon R, Burda P, Seyyedi S, Debus V, Socha P, Sykut-Cegielska J, van Spronsen F, de Meirler L, Vajro P, DeClue T, Ficicioglu C, Wada Y, Wevers R, Vanderschaeghe D, Callewaert N, Fingerhut R, van Schaftingen E, Freeze H, Morava E, Lefeber DJ# & Marquardt T#. Multiple phenotypes in phosphoglucomutase 1 deficiency. New England Journal of Medicine, 2014;370(6):533-42.

Van Scherpenzeel M, Timal S, Rymen D, Hoischen A, Wuhrer M, Hipgrave-Ederveen A, Grunewald S, Peanne R, Saada A, Edvardson S, Grønborg S, Ruijter G, Kattentidt-Mouravieva A, Brum JM, Freckmann ML, Tomkins S, Jalan A, Prochazkova D, Ondruskova N, Hansikova H, Willemsen MA, Hensbergen PJ, Matthijs G, Wevers RA, Veltman JA, Morava E, Lefeber DJ. Diagnostic serum glycosylation profile in patients with intellectual disability as a result of MAN1B1 deficiency. Brain 2014;137:1030-8.


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Research Theme 2:
Perception, Action and Decision-making

Donders
Research Group
Glycosylation Disorders in Neurology


Principal Investigator
Prof. Dr. Dirk Lefeber

Assistant Professor
Dr. Monique van Scherpenzeel

Postdocs
Dr. Mohammad Alsady
Dr. Hans Wessels

PhD students
Nurulamin Abu Bakar
Marjolein van den Boogert
Federica Conte
Sharita Timal
Anke Willems
Paola de Haas
Jos Jansen
Lars Elmann Larsen
Susette Lauwen
Walinka van Tol

Research technicians
Esther Hermans
Anouk Suppers