Department of Neurosciences
Case Western Reserve University
School of Medicine, Room E653
The laboratory combines a primary interest in CNS neural development with a focus on understanding the biology of neural diseases including Multiple Sclerosis, Brain tumors and Cerebral Palsy.
We are interested in understanding the cellular and molecular mechanisms that regulate glial cell determination in the developing vertebrate CNS. Oligodendrocytes, the myelinating cells of the CNS develop from precursors that arise in distinct locations within the embryonic neural tube. The origin of oligodendrocyte precursors is a result of local signaling including expression of sonic hedgehog. A number of other influences are required to develop the final pattern of oligodendrocyte in the mature tissue. These include dispersal signals to guide cell migration and stop signals such as the chemokine CXCL1 that position precursors to receive appropriate proliferative and differentiative cues. We are currently defining the interplay between these different signals in order to gain a complete understanding of oligodendrogenesis.
Precursor cells capable of giving rise to oligodendrocytes persist in the adult CNS and we are using a variety of approaches to determine whether these endogenous cells can be recruited to enhance repair of damaged white matter in the adult CNS. These include stimulation of cell proliferation and survival through delivery of specific proteins into focal lesions and the use of transgenic mice lacking critical components of the chemokine signal pathways.
The majority of primary brain tumors are derived from glial lineage cells. Using information derived from out developmental studies we are determining whether distinct populations of brain tumors proliferate migrate and die in response to selected stimuli.
Cerebral Palsy is a commonly associated with insults to the developing CNS that result in aberrant development of myelinated regions. We are testing the hypothesis that the failure of normal development reflects a transient perturbation in the development of oligodendrocyte precursors. We have recently developed a novel model of fetal ischemia in rats and are using this model to develop interventional therapies to reduce the damage of prenatal insults.