We are interested in understanding how the nervous system develops
from a cluster of similar progenitors, and adapts to an ever-changing
world developmentally, and what this can teach us about regeneration
in other parts of the nervous system.
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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