Our lab seeks to get insight in the molecular and cellular basis of learning and memory formation. Central to our approach is the use of genetically engineered mice as a tool to dissect these mechanisms. We are particularly interested in hippocampal plasticity and hippocampus dependent learning, as well as in the mechanisms underlying intellectual disabilities. Mutation-induced changes are analyzed at the biochemical, cellular and behavioral level. By analyzing the mutant mice at all these levels we hope to understand the specific function of these genes and proteins in synaptic plasticity, and to get insight in the molecular mechanisms underlying learning and memory. This knowledge is essential to develop treatments for patients with (genetic) diseases that affect normal brain function. To translate our findings to the patients, we are part of the ENCORE expertise center for neuro-developmental disorders, for which Ype Elgersma is the scientific director. The genes and proteins that we focus on are CaMKII, UBE3A and proteins belonging to the RAS-ERK-MTOR signaling pathway. The associated diseases are Angelman Syndrome, Neurofibromatosis (NF1), Noonan syndrome, Costello syndrome, Cowden disease and Tuberous Sclerosis (TSC).
- Silva-Santos et al. Ube3a reinstatement identifies distinct developmental windows in a murine Angelman syndrome model. J. Clin. Invest. 2015 (pubmed)
- Omrani et al. HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1. Mol. Psych. 2015 (pubmed)
- Goorden et al. Intact neuronal function in Rheb1 mutant mice: implications for TORC1-based treatments. Hum. Mol. Genet. 2015 (pubmed)
- Achterberg et al. Temporal and region-specific requirements of aCaMKII in spatial and contextual learning. J. Neurosci. 2014 (pubmed)
- Van der Vaart et al. Simvastatin for cognitive deficits and behavioural problems in patients with NF1 (NF1-SIMCODA): a randomised, placebo-controlled trial. Lancet. Neurol. 2013 (pubmed)
- Abs et al. TORC1-dependent epilepsy caused by acute biallelic Tsc1 deletion in adult mice. Ann. Neurol. 2013 (pubmed)
- Van Woerden et al. Beta-CaMKII controls the direction of plasticity at parallel-Purkinje cell synapses. Nature Neurosci, 2009 (pubmed)
- Krab et al. Effect of simvastatin on cognitive functioning in children with Neurofibromatosis type 1: a randomized controlled trial. JAMA 2008(pubmed)
- Goorden et al. Cognitive deficits in Tsc1 mice in the absence of cerebral lesions and seizures. Ann. Neurol. 2007, 62, 648-655 (pubmed)
- Hojjati et al. Kinase activity is not required for alphaCaMK2-dependent presynaptic plasticity at hippocampal CA3-CA1 synapses. Nature Neurosci. 2007 (pubmed)
- Van Woerden et al. Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of CaMKII inhibitory phosphorylation. Nature Neurosci 2007 (pubmed)
- Hansel et al. AlphaCaMK2 Is essential for Cerebellar LTD and motor learning. Neuron 2006 (pubmed)
- Master students: please inquire for research opportunities.