Dr. E. de Graaff
Cell Biology, Department of Biology
Faculty of Science, Utrecht University
Kruytgebouw, room Z501
Esther de Graaff studied biomedical sciences in Leiden. She performed her graduate research at the Department of Clinical Genetics at the Erasmus University in Rotterdam and received her Ph.D. in 1996. As a postdoctoral fellow she worked in the laboratory of Dr. Vassilis Pachnis at the National Institute of Medical Research, London, UK. In 2001, she started her own research group at the Department of Clinical Genetics at the Erasmus MC and moved in 2009 to the Department of Neurocience, Erasmus M. In 2011 she moved to Utrecht University where she is now Assistent Professor in the Department of Biology. She is recipient of an EMBO Long Term Fellowship (1997) and a ZonMW-VIDI (2005).
In general our group is interested in getting a better understanding of how the brain both develops and functions. Neurodevelopment encompasses many different processes, such as neurogenesis, migration and differentiation. Precursors of neurons are generally formed in one position in the brain, but have to migrate to their right location. This requires many components, such as extracellular matrix proteins, guiding the neuron in the proper directions but also intracellular proteins, such as a fully functional microtubule network with its interacting proteins. We mainly study migration defects that are caused by defective motor proteins or their adaptors. The differentiation of the neuron is mainly studied with an emphasis on the emergence of the dendrites and axon: what determines where the axon is formed and which proteins are involved in maintaining the neuron’s polarity.
We also study anomalies of the brain in adults (in close collaboration with Prof. Dr. Sillevis-Smitt from the department of Neurology, Erasmus MC, Rotterdam). More specifically we are interested in an anomaly that is characterized by sub acute onset of short-term memory loss, psychiatric symptoms, confusion and seizures and can be caused by an autoimmune inflammation of the brain. So far autoimmune antibodies targeting a variety of different intracellular or extracellular proteins have been identified. However, in a large number of patients, with auto-antibodies recognizing neuronal proteins, the epitope is unknown. A second goal of our lab therefore is the identification of these proteins. Besides identifying these proteins, we also aim to get a better understanding of both the disease mechanism and the effect of the antibodies on neuronal functioning.
van Coevorden-Hameete MH, Titulaer MJ, Schreurs MW, de Graaff E, Sillevis Smitt PA, Hoogenraad CC. Detection and Characterization of Autoantibodies to Neuronal Cell-Surface Antigens in the Central Nervous System. Front Mol Neurosci. 2016 May 31;9:37.
Kevenaar JT, Bianchi S, van Spronsen M, Olieric N, Lipka J, Frias CP, Mikhaylova M, Harterink M, Keijzer N, Wulf PS, Hilbert M, Kapitein LC, de Graaff E, Ahkmanova A, Steinmetz MO, Hoogenraad CC. Kinesin-Binding Protein Controls Microtubule Dynamics and Cargo Trafficking by Regulating Kinesin Motor Activity. Curr Biol. 2016 Apr 4;26(7):849-61.
van Beuningen SF, Will L, Harterink M, Chazeau A, van Battum EY, Frias CP, Franker MA, Katrukha EA, Stucchi R, Vocking K, Antunes AT, Slenders L, Doulkeridou S, Sillevis Smitt P, Altelaar AF, Post JA, Akhmanova A, Pasterkamp RJ, Kapitein LC, de Graaff E, Hoogenraad CC. TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays. Neuron. 2015 Dec 16;88(6):1208-26.
Jaarsma D, van den Berg R, Wulf PS, van Erp S, Keijzer N, Schlager MA, de Graaff E, De Zeeuw CI, Pasterkamp RJ, Akhmanova A, Hoogenraad CC. A role for Bicaudal-D2 in radial cerebellar granule cell migration. Nat Commun. 2014 Mar 11;5:3411.
Spangler SA, Schmitz SK, Kevenaar JT, de Graaff E, de Wit H, Demmers J, Toonen RF, Hoogenraad CC. Liprin-α2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission. J Cell Biol. 2013 Jun 10;201(6):915-28.
De Graaff E, Maat P, Hulsenboom E, van den Berg R, Demmer J, Lugtenburg PJ, Hoogenraad CC, Sillevis Smitt P (2012) “Identification of delta/notch-like epidermal growth factor-related receptor as the Tr antigen in paraneoplastic cerebellar degeneration.” Ann Neurol 71(6):815-24.
Schlager, M. A., L. C. Kapitein, I. Grigoriev, G. M. Burzynski, P. S. Wulf, N. Keijzer, et al. (2010). “Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis.” EMBO J 29(10): 1637-51.