1. Study of neurogenetic genes. We have identified and are currently studying the neuron-specific gene BM88, which has neurogenetic properties and is involved in the exit of proliferating neuroblasts from the cell cycle and their differentiation towards a neuronal phenotype, both in vitro and in vivo. BM88 is an intracellular membrane protein with PXXP motifs, like the p53 family of proteins, and SH3-binding domains. It is located at the external membrane of mitochondria, in the endoplasmic reticulum and other intracellular organelles while the bulk of the protein faces the cytoplasm. BM88 not only contributes to the exit from the cell cycle and the initiation of differentiation, but it also appears to protect cells from apoptosis. Using BM88 as a paradigm, we are interested in understanding aspects of brain development and differentiation as well as in delineating the signaling pathways underlying these phenomena. The scientific approaches we use include:
  
1.1 Study of neurogenetic genes, their transcriptional activation and target genes, in genetic models of transgenic animals with targeted and regulated expression of the gene of interest (eg. Tet ON/OFF systems).
 
1.2  Induction of neurogenesis in genetically modified Νeural Stem Cells by infection with recombinant retroviruses and lentiviruses that drive the expression of gene(s) of interest, in order to analyze their neurogenetic potential and use them to enhance neurogenesis and functional recovery in animal models of neurodegenerative diseases.
 
1.3  Induction of neurogenesis in post-mitotic cells using recombinant adenoviruses, aiming at gene therapy of neurodegenerative diseases and the prevention of ageing.
 
1.4  Identification of neurogenetic signaling molecules with the use of microarrays, two-yeast hybrid systems and proteomics.


2. Study of the molecular and cellular mechanisms regulating myelination.
Myelination is regulated through neuron-glia inter-actions. We are currently studying the role of recombinant, genetically modified cell adhesion molecules, such as NCAM, PSA-NCAM, F3, L1, as well as, the involvement of neurotrophic factors in the regulation of cell migration and axonal myelination. Our models include in vitro systems of primary cell cultures and organotypic slices which permit assessment of cell migration and myelination. In addition, myelinating precursor cells and Schwann cells over-expressing the above proteins with the use of viral gene transfer are tested in animal models of experimental injuries or de-myelination.