With few notable exceptions, the adult mammalian brain is devoid of physiological neurogenesis, and therefore lacks significant regenerative capacity. Our laboratory is interested in developing strategies of reinstalling neurogenesis in brain areas such as the cerebral cortex where neurogenesis completely ceases once embryogenesis is completed. We pursue this goal by rewiring the gene regulatory networks of brain glia such as astrocytes and oligodendrocyte precursor cells by introducing neurogenic transcription factors to turn them into induced neurons. A main thrust of our research is to promote the generation of specific subtypes of induced neurons in vivo by so-called proneural transcription factors. For instance, by inducing the generation of new interneuron-like cells from glia, we hope to be able to eventually restore diseased brain circuits such as found in neurodevelopmental disorders or epilepsy.
To fully understand the potential and limitations of induced glia-to-neuron conversion, we scrutinize the transcriptome changes that occur during this process at single cell level. Using in vivo live imaging, we wish to link molecular changes to specific stages of the morphological metamorphosis. This will enable us to identify molecular and cell biological road blocks to successful fate conversion and provide us with molecular targets to further improve it. Finally, we investigate the recruitment of induced neurons into functional brain circuits by using electrophysiology and imaging. We hope that our research will thus pave the way for urgently needed new strategies for repairing diseased brain circuits.