Coates Family Professor of Neuroscience
Our research is focused on understanding the molecular mechanisms of cellular differentiation in the nervous system. To this end, we are developing and applying DNA microarray-based approaches to identify on a genome-wide level the genes and genetic programs that underlie the progression of cells from the undifferentiated stem cell to the mature cell state. The information gained from these studies will be used to interpret and guide future studies on the development of neuronal precursors and mature neurons from human embryonic stem cells. We are focusing on two model systems for our studies.
In the first, we are utilizing the murine olfactory epithelium (OE) to study principles of adult neurogenesis and neuronal stem cells. The OE has many advantages for studying neurogenesis, as its neurons are regenerated throughout the life of the animal and following injury through the proliferation and differentiation of progenitor or stem cells. However, little is known about the identity of these stem cells. We are carrying out whole genome expression profiling with DNA microarrays to identify functional stem cell markers in the mouse OE with the ultimate goal of identifying genes that regulate neuronal stem cell maintenance and/or differentation.
In the second approach, we are studying neurogenesis in the mammalian olfactory bulb (OB), with an emphasis on the developmental potential of OB radial glia. The discovery that radial glia can be neural progenitors is one of the most important recent advances in our understanding of neural development. Once thought of primarily as scaffolding to direct the migration of immature neurons, radial glia are also a source for these cells during embryogenesis. Moreover, radial glia produce the astroglia that function as neural progenitors in the adult subventricular zone, and procedures that successfully generate neurons from embryonic stem cells proceed through a radial glial intermediate. Elucidation of the functional properties of radial glia in neurodevelopment will provide information crucial for the eventual development of embryonic stem cell-based therapies for neurological diseases.