Professor of Molecular Biology, Director at the Max Planck Institute for Experimental Medicine
Major Research Interests
We are interested in the mechanisms of neuron-glia interactions in the higher nervous system, and in the genes that are required for normal glial cell function. Here, transgenic and mutant mice have become important to study developmental processes as well as genetic diseases. For example, oligodendrocytes are glial cells highly specialized for enwrapping CNS axons with multiple layers of membranes, known to provide electrical insulation for rapid impulse propagation. We found that oligodendrocytes are also essential for maintaining the long-term integrity of myelinated axons, independent of the myelin function itself. The mechanisms by which oligodendrocytes support long-term axonal survival are still under investigation. The importance of glial cells as the "first line of neuroprotection", however, is illustrated by several myelin-associated diseases in which axonal neurodegeneration contribute to progressive disability. These range in humans from peripheral neuropathies (CMT1) to spastic paraplegia (SPG2), and presumably multiple sclerosis (MS) and certain forms of psychiatric disorders. We are developing transgenic animal models for some of these diseases, in order to dissect the underlying disease mechanisms and, in the case of CMT1A, have used these models to design novel therapeutic strategies.
The glial "decision" to myelinate an axonal segment is partly controlled by the axon itself, but the signaling mechanism is not understood. We have found that axonal neuregulin-1 (NRG1) is the major determinant of myelination in the peripheral nervous system. We are now investigating NRG1 dysregulation also in CNS myelination, using quantifiable behavioural functions in mice. By combining genetics with enviromental risk factors for schizophrenia (in collaboration with H. Ehrenreich) we will explore the hypothesis that NRG1, a known human schizophrenia susceptibility gene, points to an important role of myelinating glia in some psychiatric disorders.
Future Projects and Goals
Mechanisms of neuron-glia signalling; function of myelin proteins and lipids; transcriptional profiling of single cells in vivo; novel mouse models of neuropsychiatric disorders.
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Selected Recent Publications