Grant: Project Grant

The discovery of neural stem cells (NSCs) in the brains of all mammals, including humans, overturned the dogma that the brain is devoid of regenerative capacity. This discovery raised the exciting possibility of using the regenerative capacity of the brain and stem cell-based therapies to replace damaged brain cells and to cure neurodegenerative diseases and brain trauma. Although promising, the use of NSCs to heal these devastating diseases is far from a given, and the promises of stem cell-based therapies cannot be fully realized without understanding the mechanisms that regulate NSC activity and how NSCs integrate and decode different molecular and cellular signals required either for the maintenance of their quiescent, dormant state or for inducing their activation and generation of new cells. In this project using mouse models, advanced imaging and genetic tools, in vivo monitoring of stem cells activity and pharmacological and genetic modulations of their microenvironment, we will study intrinsic mechanisms underlying maintenance of quiescent state, entry of stem cells into the proliferative phase and the role of different microenvironmental cues in stem cells physiology. Our study will allow for better understanding of the mechanisms that maintain stem cells quiescence and control their proliferation. This, in turn, will provide new strategies to increase neurogenesis and "turn on" brain regenerative capacity to heal devastating neurodegenerative diseases and brain trauma.