The department studies the presynaptic nerve terminal in health and disease and also contributes to the understanding of complex traits in rodents and humans.
In our studies of the nerve terminal, we aim to understand the gene networks that orchestrate the secretion of diverse chemical signals such as classical neurotransmitters from synaptic vesicles and large dense core vesicles. In our complex trait studies we aim to systematically dissect complex behavior, especially cognition, in terms of the underlying network of latent traits, gene networks, genetic variation and environmental factors and to understand disease mechanisms.
For our secretion studies, we use model organisms. Mostly mutant mice and in vitro preparations, such as primary neurons and secretory cells in culture. These models are studied, using a variety of functional assays. They range from electronmicroscopy, molecular biology, protein chemistry and immunocytochemistry to life cell imaging, electrophysiology and behavioral phenotyping. We use both human and mouse populations for our complex trait studies: clinical cohorts, twins and samples from the general population and common inbred mouse lines, recombinant inbred lines, transposon mice and knock-out/knock-in mice. We study these populations, using genome wide association studies, gene network analyses and phenotypic modelling. We also apply high-throughput, automated behavioral assessments in rodents.
Please see also: http://www.cncr.nl/people/staff_u-z/verhage_m_-_professor
Groffen AJ., Martens S., Díez Arazola R., Cornelisse LN., Lozovaya N., de Jong AP., Goriounova NA., Habets RL., Takai Y., Borst JG., Brose N., McMahon HT., Verhage M. (2010) Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release. Science , 327 (5973): 1614-8.
Mohrmann R., de Wit H., Verhage M., Neher E., Sørensen JB. (2010) Fast vesicle fusion in living cells requires at least three SNARE complexes. Science , 330 (6003): 502-5.
de Wit H., Walter AM., Milosevic I., Gulyás-Kovács A., Riedel D., Sørensen JB., Verhage M. (2009) Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes. Cell , 138 (5): 935-46.
Gerber SH., Rah JC., Min SW., Liu X., de Wit H., Dulubova I., Meyer AC., Rizo J., Arancillo M., Hammer RE., Verhage M., Rosenmund C., Südhof TC. (2008) Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science , 321 (5895): 1507-10.
Wierda KD., Toonen RF., de Wit H., Brussaard AB., Verhage M. (2007) Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Neuron ., 54 (2): 275-90.
2013 VU research fellowship
2012 ERC Ideas Advanced Grant
2003 Chairman of the directory board CNCR
2001 Pionier/VICI laureate of the Dutch Organization for Scientific Research (NWO)
1990 PhD title ´cum laude´, Amsterdam University