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Regulation of neural stem cells: Studying the cellular and molecular regulation of different subpopulations of progenitors within the olfactory epithelium has lead us to two pathways that may play a role in maintaining neural stem cells in fixed states in the brain. One (SPARC: Secreted Protein rich in Cysteines) is a matricellular protein that we are testing for its ability to directly control the matrix and growth factor environments of neural stem cells. Another, BLBP (FABP7) is an intrinsic pathway that may be involved in the regulation of a glial-based neural stem cell niche. Glial-based mechanisms of regeneration: The failure of the CNS to regenerate is due, in large part, to an uncooperative glial environment that does not support axonal re-growth and targeting. An exception to this is found the mammalian olfactory system, where olfactory ensheathing cells (OECs), continuously promote axonal re-growth of olfactory receptor neurons (ORNs) across the PNS:CNS boundary.We have shown that OECs transplanted into the spinal cord can impact their lesion environment via the secretion of factors that modulate the extracellular biochemical milieu, and change the immune response to lesion. We are now investigating microglial-based mechanisms that may contribute to protection and regeneration following spinal cord injury and stroke. Epigenetic regulation of Neuronal Differentiation: How neurons at different stages of development regulate their population by selective apoptosis, is a long-standing question in the lab that has lead to the identification of key transition points between changes in neuronal state that are moments of apoptotic vulnerability. These transitions appear to be regulated epigenetically by a sequence of events that change the structure of chromatin within a developing neuron, and involve de novo methyl transferases, methylDNA binding proteins, Histone deacetylases and their corepressor complex members. How these factors modulate gene expression states at sequential stages of development is a growing and active area of interest in the lab. The Roskams Lab is essentially split into research groups ( the "neural stem cell bay" the "glia and regeneration bay" and the "epigenetics bay") focussed on each of the following areas, whose interests become more intertwined the deeper we probe into some of the intrinsic mechanisms common to each. Although we no longer have an active research program in neuronal death mechanisms, neuronal protection is a key aim in many aspects of research in the three current lab groups
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