Freda Miller

A fundamental question in biology is how the mammalian brain develops from a thin sheet of neuroepithelial stem cells to a network of neuronal connectivity that is able to process sensory information and generate an appropriate output. This broad context has provided the cornerstone of my research over the entirety of my independent career as a molecular/cellular neuroscientist who is interested in development and repair of the nervous system. I propose to continue this work over the upcoming seven years. Specifically, I propose to define the molecular/cellular mechanisms that regulate neurogenesis during normal and pathological brain development and to determine how neuronal survival and connectivity are maintained over the mammalian lifespan. Much of this work will be pursued with my close collaborator Dr. David Kaplan. In addition, I will continue to study mammalian tissue regeneration, utilizing an adult murine digit tip model that we recently established, and focusing on (i) nerve-derived precursor populations and (ii) on the endogenous dermal stem cells that we discovered and characterized (skin-derived precursors or SKPs). Finally, I will continue to facilitate the transfer of our basic research findings to commercial and clinical endpoints by establishing and leading teams of individuals with relevant and complementary expertise, as exemplified by our ongoing efforts to use metformin for human brain repair. It is my overall goal to continue to provide fundamental biological insights, with the hope that they will ultimately lead to development of novel therapeutic strategies.