Jeroen Pasterkamp
Position: Assistant 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 the signaling events and regulatory mechanisms involved in the formation of neuronal connections during development. Our investigations concentrate on the developing mouse embryo 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.
Experimental strategy and key results:
1. Analysis of non-coding RNAs in neural circuit development using LNA array technology, high-throughput microscopy and in utero electroporation.
2. Identification of novel signaling molecules in axon growth and guidance through functional proteomics approaches, biochemistry, and molecular cell biology.
3. Studying the development of dopaminergic and striatal circuits using novel mouse genetics techniques, neuroanatomy, FACS, live cell imaging, and in vitro assays.
4. Molecular basis of ALS pathology (in collaboration with Dept. Neurology, UMCU) using mouse genetics, cell biology and stem cell technology.
RECENT KEY PUBLICATIONS
1. 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.
2. van Es MA, Veldink JH, Saris CG, Blauw HM, van Vught PW, Birve A, Lemmens R, Schelhaas HJ, Groen EJ, Huisman MH, van der Kooi AJ, de Visser M, Dahlberg C, Estrada K, Rivadeneira F, Hofman A, Zwarts MJ, van Doormaal PT, Rujescu D, Strengman E, Giegling I, Muglia P, Tomik B, Slowik A, Uitterlinden AG, Hendrich C, Waibel S, Meyer T, Ludolph AC, Glass JD, Purcell S, Cichon S, Nöthen MM, Wichmann HE, Schreiber S, Vermeulen SH, Kiemeney LA, Wokke JH, Cronin S, McLaughlin RL, Hardiman O, Fumoto K, Pasterkamp RJ, Meininger V, Melki J, Leigh PN, Shaw CE, Landers JE, Al-Chalabi A, Brown RH Jr, Robberecht W, Andersen PM, Ophoff RA, van den Berg LH (2009) Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nature Genetics 41, 1083-1087.
3. Zhou Y, Gunput RA and Pasterkamp RJ (2008) Semaphorin signaling: progress made and promises ahead. Trends Biochem Sciences 33, 161-170.
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.
