RESEARCH FOCUS
My research focuses on (but is not limited to) transcription regulatory mechanisms that link gene regulation in the nucleus to distal information processing in neurites and synapses. I’m particularly interested in the induction of neurite outgrowth after neuronal injury, the formation and plasticity of central neuronal synapses, and synaptic dysregulation in aging-related neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease.

1. Transcription factors that control regenerative neurite outgrowth.
In contrast to the peripheral nervous system, neurons in the central nervous system fail to regenerate injured axons. Using the sensory neurons in the rat dorsal root ganglion as a model system we identified several transcription factors that may play a role in successful neuronal regeneration. We showed for instance that the bZIP transcription factor NFIL3 represses regenerative neurite outgrowth by interfering with CREB-mediated gene transcription. We currently try to reconstruct the transcription regulatory network underlying successful neuronal regeneration using experimental and computational approaches, and to identify key transcription factors that may be used to promote regeneration of injured central neurons.

2. Molecular mechanisms underlying synapse formation and synaptic plasticity.
Neurons need to dynamically change the strength of their connections in order to respond to and retain memory for particular stimuli. These changes occur at synapses and require synapse autonomous molecular mechanisms, but also changes in nuclear gene expression. We currently use several transgenic mouse models to study both synapse autonomous and transcription-dependent mechanisms underlying synapse formation, synapse function and synaptic plasticity.

3. Novel target genes and proteins for Parkinson’s and Alzheimer’s disease.
Parkinson’s and Alzheimer’s disease are the two most prevalent neurodegenerative disorders and are characterized by the progressive loss of specific populations of neurons. The reasons for the selective vulnerability of these neurons is not clear. Using in vitro cellular models one hand, and in vivo genetic and pharmacological mouse models on the other hand, we try to identify molecular markers of early, presymptomatic Alzheimer’s and Parkinson’s disease. In addition, we study DNA damage repair defective mouse models for early aging. The focus of our research is on early synaptic changes that may form a common denominator in all forms of aging-related neurodegeneration.