We study the pathways that regulate cell proliferation and fate in the stem cell niches within the adult brain. Using both cutting-edge and classical cell biology techniques, we measure signaling in neural stem cells and brain tumor cells. We work in human tissue and animal models to identify and target subpopulations of cells that are responsible for the generation of specific neuronal subtypes (in the normal brain) and for tumor growth and progression (in gliomas and other tumor types).
Unlike many other organs, the brain has very few dividing cells, and when neurons are lost because of disease or injury they generally are not replaced, causing devastating consequences for patients with neurodegenerative disorders, traumatic brain injuries, or other diseases. Understanding how stem cells are normally directed to make particular neurons (or other cells) will be essential to reprogramming these cells for therapeutic purposes. In addition, because stem and progenitor cells are some of the only proliferating cells in the brain, they are a likely cell of origin for brain tumors in both children and adults.
Neural stem cells survive in two locations in the adult brain. Although these cells can generate many thousands of cellular progeny, their proliferation is normally tightly controlled. Many signals – growth factors, neurotransmitters, morphogens, and others – have been suggested to affect these stem cells, but we still have a limited understanding of how a normal stem cell is driven to self-renew, proliferate, and make specific types of mature cells in the brain. Likewise, although many of these same signals are affected by mutations in brain tumors, we do not fully understand the molecular pathways driving brain tumor growth and invasion. We use single-cell-level assays to measure the effects of specific molecular signals on proliferation, differentiation, and invasion, with the goal of identifying pathways that can be targeted for therapeutic purposes.
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