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Small Molecule Manipulation of Neural Stem Cells

RESEARCH PROJECT: 
In Progress

In mammalian cells, G-quadruplexes are nucleic acid secondary structures that are found throughout both the genomic DNA and RNA transcriptome. These structures regulate gene expression levels and genome replication through many different mechanisms. Several studies have identified small molecules that can bind and modify the stability of G-quadruplexes. Because the function of a cell is strongly tied to the levels of the specific genes it expresses, small molecules that modify G-quadruplex stability can be potent manipulators of cell function. In the nervous system, our knowledge of how G-quadruplexes influence neural gene expression and neural cell function is limited. Recent studies in our laboratory show that a subset of small molecules that target G-quadruplex stability can alter the proliferation and differentiation of neural stem and progenitor cells isolated from the adult mouse subventricular zone. We are currently pursuing studies to establish the mechanisms by which these molecules can alter the proliferation and differentiation of neural stem and progenitor cells, as well as establish that these molecules are a novel class of compounds for manipulating neural stem cells in order to generate neuronal progenitors suitable for treating neurological disease and injury.