Research
Neural stem cells: the building blocks of the nervous system
During development, neural stem cells (NSCs) generate all neurons in the brain and spinal cord, as well as astrocytes and oligodendrocytes - glial cells that play critical roles in the correct formation and functioning of the nervous system. This process continues in several regions of the adult mammalian brain, including the subventricular zone (SVZ) of the lateral ventricles. While adult NSCs in the SVZ largely produce neurons, SVZ gliogenesis dramatically increases following injury or disease, especially in the case of demyelinating disorders. Demyelination – damage and/or loss of the myelin sheaths surrounding axons – occurs in a large variety of central nervous system insults, pathologies, and neurodegenerative diseases, including Multiple Sclerosis (MS).
Current therapies for relapsing-remitting MS can be effective in reducing symptoms to an extent, but have little impact on promoting remyelination, or regeneration of myelin sheaths. Oligodendrocyte progenitor cells (OPCs) located throughout the brain participate in endogenous remyelination of lesions, migrating to the injury site and maturing into myelinating oligodendrocytes, albeit at low levels. An additional source of OPCs following injury is NSC-derived OPCs generated in the SVZ. Interestingly, there is evidence that these NSC-derived OPCs demonstrate greater propensity to differentiate into oligodendrocytes and generate thicker myelin sheaths. Understanding the molecular mechanisms driving these processes of regeneration is critical in order to harness their full potential in vivo for repair and to define new avenues for therapeutic interventions.
Our lab investigates signaling pathways that regulate glial progenitor cells from development to the aged adult brain. We aim to understand NSC and OPC heterogeneity, and whether they exhibit distinct functional properties in the healthy and injured brain. We use advanced mouse genetics and injury models, human tissue samples, and single cell transcriptomics to study the question: how do endogenous stem and progenitor cells in the brain respond to injury and disease?