Genes, Development And Behavior
Department of Translational Neuroscience
Utrecht, The Netherlands

Jeroen Pasterkamp

Position: Professor of Translational Neuroscience
E-mail: r.j.pasterkamp@umcutrecht.nl
Phone:  (+31) (0)88 75 68831
Phone secretariat: (+31) (0)88 75 68810 
www.jeroenpasterkamplab.com

The focus of my laboratory is directed towards understanding 1) the signaling events and regulatory mechanisms involved in the formation of neuronal connections during development, and 2) why specific neural circuits are altered or lost in neurological disease. Our investigations concentrate on the mouse and humanized cell culture models using an integrated approach involving molecular cell biology, microscopy and genetics. Our group is leading the MIND facility for neural iPSC, brain organoids and light sheet microscopy.

 

RESEARCH 

Aims:

Disturbed neuronal connectivity is a hallmark of many neural disorders. For example, abnormal wiring of the hippocampus during epileptogenesis is believed to contribute to pathophysiology of epilepsy, while neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) are characterized by a marked loss of neuronal connections. To better understand and treat these situations of perturbed neuronal connectivity further insight is needed into the mechanisms that normally control nervous system wiring. The aim of our research is to determine how neuronal connections are formed at the molecular, cellular and systems level, and how and why they are changed in situations of disease.

Experimental strategy and key results:

1. Identification of novel signaling molecules in axon growth and guidance through functional proteomics approaches, biochemistry, and molecular cell biology.

2. Studying the development of dopaminergic circuits using novel mouse genetics techniques, neuroanatomy, FACS, live cell imaging, and in vitro assays.

3. Molecular basis of ALS pathology using mouse genetics, cell biology and stem cell technology.

4. Analysis of non-coding RNAs in neuronal network changes underlying epilepsy using RNAseq, high-throughput microscopy, and cell biological approaches.


RECENT KEY PUBLICATIONS

 

1. Kong Y, Janssen BJ, Malinauskas T, Vangoor VR, Coles CH, Kaufmann R, Ni T, Gilbert RJ, Padilla-Parra S, Pasterkamp RJ*, Jones EY* (2016). Structural Basis for Plexin Activation and Regulation. Neuron 91, 548-60.

2. Van Erp S, van den Heuvel DMA, Fujita Y, Robinson R, Hellemons AJCGM, Adolfs Y, Van Battum EY, Blokhuis AM, Kuijpers M, Demmers J, Hedman H, Hoogenraad CC, Siebold C, Yamashita T, Pasterkamp RJ (2015) Lrig2 negatively regulates ectodomain shedding of axon guidance receptors by ADAM proteases. Developmental Cell, 35, 537-552.

3. Van Battum EY, Brignani S, Pasterkamp RJ (2014) Axon guidance proteins in neurological disease. Lancet Neurology, 14, 532-546.

4. Schmidt ER, Brignani S, Adolfs Y, Lemstra S, Demmers J, Vidaki M, Donahoo AL, Lilleväli K, Vasar E, Richards LJ, Karagogeos D, Kolk SM, Pasterkamp RJ (2014) Subdomain-mediated axon-axon signaling and chemoattraction cooperate to regulate afferent innervation of the lateral habenula. Neuron, 83, 372-387.

5. Van Battum EY, Gunput RA, Lemstra S, Groen EJ, Yu KL, Adolfs Y, Zhou Y, Hoogenraad CC, Yoshida Y, Schachner M, Akhmanova A, Pasterkamp RJ (2014) The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fiber connections. Nature Communications, 5, 4317.

 

 

PUBLICATIONS