Dineke Verbeek, PhD
Rosalind Franklin Fellow, Associate professor
MSc: Medical Biology, University of Utrecht, 2000
PhD: The localization and identification of novel SCA genes in the Dutch autosomal dominant cerebellar ataxia population, Utrecht University, 2005, pdf
News: Appointed associate professor per 1 January 2017
Phone: + 31 (0)6 52724553
Keywords: Brain disorders, genetics, neuroscience, neurodegeneration, cell biology, and molecular biology
Dineke graduated from Utrecht University (NL) with an MSc in Medical Biology in 2000 (w ith merit). Then she joined the research group of Prof. Richard Sinke at the Department of Genetics (Utrecht University) to work towards her PhD thesis on “The localization and identification of novel spinocerebellar ataxia genes in the Dutch autosomal dominant cerebellar ataxia population”. During her PhD studies, she made a significant contribution to the field of human genetics in spinocerebellar ataxia by identifying two novel SCA types (SCA19 and SCA23) and her work increased insight into the pathogenesis of SCA14 in cell model systems. For this last study, she was awarded a pre-doctoral fellowship from the National Institutes of Health to work in the laboratory of Prof. Kenneth Fischbeck (NIH, Bethesda, MD, USA).
After completing her PhD in 2005, Dineke joined the laboratory of Dr. Eric Reits, Department of Cell Biology and Histology at the Academic Medical Center in Amsterdam, where she successfully followed up on her PhD work on SCA14. In 2008, Dineke was awarded a prestigious Rosalind Franklin Fellowship by the University of Groningen to establish her own independent research group focusing on unraveling the genetics and biological mechanisms underlying movement disorders, with special attention on the spinocerebellar ataxias.
We aim to better understand the underlying aetiology of movement disorders, neurodegenerative disorders, and congenital brain disorders by discovering the genes and biological mechanisms that regulate neurodevelopment and neuronal survival in the brain. We are also exploring how the mutant genes disrupt these mechanisms and lead to disease. Likewise, we aim to identify the shared molecular mechanisms leading to different brain disorders.
The goal of our research is to learn more about the genetic and molecular mechanisms underlying brain disorders, with a focus on the diseases of the cerebellum such as the spinocerebellar ataxias. For the last few years, our team has been at the forefront of identifying SCA genes in European populations, including SCA19 and SCA23 genes. We are using the latest next generation sequencing technologies to identify disease genes for Mendelian forms of dystonia, spinocerebellar ataxias, and congenital brain disorders. We are adopting a multi-disciplinary approach, combining genetics, cell model systems and mouse models to identify the molecular mechanisms underlying these brain disorders.
One of our research lines focuses on spinocerebellar ataxia type 23 (SCA23). Earlier, we discovered that mutations in Prodynorphin (PDYN) cause SCA23 and lead to cerebellar neurodegeneration and ataxia in humans and mice. PDYN is the precursor molecule for the opioid peptide dynorphins. Dynorphins play a crucial role in how we sense pain, and how we respond to addictive substances, but unexpectedly they also exhibit an as yet unrecognized role in the survival of cerebellar neurons. We are currently exploring the underlying molecular mechanisms by which mutant PDYN leads to neuronal cell death and cerebellar ataxia in cell model systems in which we have introduced human mutations in endogenous Pdyn using CRISPR-Cas9 technology. more
3 key publications
Elevated mutant dynorphin A causes Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type. Smeets CJLM, Jezierska J, Watanabe H, Duarri A, Fokkens MR, Meijer M, Zhou Q, Yakovleva T, Boddeke E, den Dunnen W, van Deursen J, Bakalkin Q, Kampinga HH, van de Sluis B, and Verbeek DS. Brain 2015 Sep;138(Pt 9):2537-52. Abstract
Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19. Duarri A, Jezierska J, Fokkens M, Meijer M, Schelhaas HJ, den Dunnen WF, van Dijk F, Verschuuren-Bemelmans C, Hageman G, van de Vlies P, Küsters B, van de Warrenburg BP, Kremer B, Wijmenga C, Sinke RJ, Swertz MA, Kampinga HH, Boddeke E, Verbeek DS. Annals of Neurol ogy 2012;72(6):870-80. Abstract
Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. Bakalkin G, Watanabe H, Jezierska J, Depoorter C, Verschuuren-Bemelmans C, Bazov I, Artemenko KA, Yakovleva T, Dooijes D, Van de Warrenburg BP, Zubarev RA, Kremer B, Knapp PE, Hauser KF, Wijmenga C, Nyberg F, Sinke RJ, Verbeek DS. American Journal of Human Genetics 2010;87(5):593-603. Free PMC article
Recent publications (2015)
First de novo KCND3 mutation causes severe Kv4.3 channel dysfunction leading to early onset cerebellar ataxia, intellectual disability, oral apraxia and epilepsy
Smets K, Duarri A, Deconinck T, Ceulemans B, van de Warrenburg BP, Züchner S, Gonzalez MA, Schüle R, Synofzik M, Van der Aa N, De Jonghe P, Verbeek DS, Baets J. BMC Medical Genet ics 2015 Jul 21;16:51. Free PMC article
Elevated mutant dynorphin A causes Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type 23
Smeets CJLM, Jezierska J, Watanabe H, Duarri A, Fokkens MR, Meijer M, Zhou Q, Yakovleva T, Boddeke E, den Dunnen W, van Deursen J, Bakalkin Q, Kampinga HH, van de Sluis B, and Verbeek DS. Brain 2015 Sep;138(Pt 9):2537-52.
Spinocerebellar ataxia type 19/22 mutations alter heterocomplex Kv4.3 channel function and gating in a dominant manner
Duarri A, Lin MC, Fokkens MR, Meijer M, Smeets CJ, Nibbeling EA, Boddeke E, Sinke RJ, Kampinga HH, Papazian DM, Verbeek DS. Cellular and Molecular Life Sciences 2015 Sep;72(17):3387-99. Free PMC article
Accumulation of rare variants in the arylsulfatase G (ARSG) gene in task-specific dystonia.
Nibbeling E, Schaake S, Tijssen MA, Weissbach A, Groen JL, Altenmüller E, Verbeek DS, Lohmann K. Journal of Neurol ogy 2015 May;262(5):1340-3.
Functional analysis helps to define KCNC3 mutational spectrum in Dutch ataxia cases
Duarri A, Nibbeling EA, Fokkens MR, Meijer M, Boerrigter M, Verschuuren-Bemelmans CC, Kremer BP, van de Warrenburg BP, Dooijes D, Boddeke E, Sinke RJ, Verbeek DS. PLoS One 2015 Mar 10;10(3):e0116599. Free PMC article
CACNA1B mutation is linked to unique myoclonus-dystonia syndrome
Groen JL, Andrade A, Ritz K, Jalalzadeh H, Haagmans M, Bradley TE, Jongejan A, Verbeek DS, Nürnberg P, Denome S, Hennekam RC, Lipscombe D, Baas F, Tijssen MA. Human Molecular Genetics 2015 Feb 15;24(4):987-93.
Our work is funded by a Rosalind Franklin Fellowship from the University of Groningen and by grants from the Prinses Beatrix Foundation, the Dutch Brain Foundation, NutsOhra, and an E-RARE grant (EU funding, ERA-Net for Research programs on Rare Diseases).
Dineke was awarded a grant by E-RARE for work on SCA-3.
"Dineke Verbeek heeft eveneens E-Rare financiering in de wacht gesleept. Haar project richt zich op een vorm van spinocerebellaire ataxie (SCA): de ziekte van Machado-Joseph (SCA-3). SCA tast de kleine hersenen aan en SCA-3 is van de 37 varianten de meest voorkomende, vertelt de onderzoekster. In Nederland gaat het om honderd tot hondervijftig patiënten." (See full article "Handen ineen voor onderzoek naar zeldzame ziekten", in Dutch)
Like to join the group?
We are always interested in enthusiastic and well-motivated MSc students looking for an internship of 5-6 months. We will plan the work in discussion with you. Upcoming PhD students should enquire about the possibilities. We have opportunities for a postdoc position if you can gain a Marie Curie or EMBO fellowship to cover your own salary. P lease email me.
|Laatst gewijzigd:||01 februari 2017 16:50|