Jeroen Pasterkamp
Position: Associate Professor
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) the pathogenic mechanisms underlying amuotrophic lateral sclerosis (ALS). Our investigations concentrate on the mouse and humanized cell culture models using an integrated approach involving molecular biology, cell biology, (in vivo) functional proteomics, imaging and genetics. These studies are carried out in close collaboration with a number of local and (inter)national laboratories.
RESEARCH
Aims:
Disturbed neuronal connectivity is a hallmark of many neural disorders. For example, abnormal wiring of the brain during development is believed to contribute to pathophysiology of disorders such as schizophrenia and autism, while neurodegenerative disorders including Parkinson's disease and 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 and striatal circuits using novel mouse genetics techniques, neuroanatomy, FACS, live cell imaging, and in vitro assays.
3. Molecular basis of ALS pathology (in collaboration with Dept. Neurology, UMCU) using mouse genetics, cell biology and stem cell technology.
4. Analysis of microRNAs in neurological disease using LNA array technology, high-throughput microscopy, and cell biological approaches.
RECENT KEY PUBLICATIONS
1. Zhou Y, Gunput RA, Adolfs Y, Fuller S, Li KW, Van der Schors RC, Smit AB, Sugden P, Hemming B, Hergovich A, Pasterkamp RJ (2011) MICAL-1 is a negative regulator of NDR-MST signaling and apoptosis. Molecular Cellular Biology, 31, 3603-3615.
2. Fenstermaker AG, Blokker AA, Bechara A, Adolfs Y, Tissir F, Goffinet A, Zou Y, Pasterkamp RJ (2010) Wnt-Planar Cell Polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem. J Neurosci 30, 16053-16064.
3. Kolk SM, Gunput RA, Tran TS, van den Heuvel DM, Prasad AA, Hellemons AJ, Adolfs Y, Ginty DD, Kolodkin AL, Burbach JP, Smidt MP, Pasterkamp RJ (2009) Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth, and intracortical targeting. J Neurosci 29, 12542-12557.
4. Suzuki K, Okuno T, Yamamoto M, Pasterkamp RJ, Takegahara N, Takamatsu H, Kitao T, Takagi J, Rennert PD, Kolodkin AL, Kumanogoh A, Kikutani H (2007) Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature 446:680-684.
5. Pasterkamp RJ, Peschon JJ, Spriggs MK, Kolodkin AL (2003) Semaphorin7A promotes axon outgrowth through integrins and MAPKs. Nature (leading article) 424:398-405.
