Research

A neural stem cell responding to the injury caused by a chemotherapy drug (Image by Michael Bonaguidi)
A neural stem cell responding to the injury caused by a chemotherapy drug (Image by Michael Bonaguidi)

A dramatic form of brain plasticity is the addition of newborn cells to existing neural circuits. Adult neurogenesis continues throughout life largely in one human brain region called the dentate gyrus of the hippocampus, a structure essential for learning, memory and cognitive ability. This process makes a significant and dynamically regulated contribution to hippocampus homeostasis and serves as a model system to resolve the complex interplay between genetics and environmental alteration within the adult brain.

Our group developed new approaches to visualize the entire neurogenesis process within the mouse hippocampus at single cell resolution. In doing so, we provided the first evidence of individual stem cell existence within the adult mammalian brain. Our subsequent studies revealed mechanisms linking neural stem cell adaptation to changes in the brain under normal conditions and during injury.

We are currently examining how neural stem cells — including a newly discovered second population — modify the brain from development to old age. These efforts are highlighted by three areas of interest: (1) How do neural stem cells adapt their behavior to meet needs of the injured or diseased brain? What are the molecular mechanisms mediating the production of newborn stem cells, neurons, astrocytes and oligodendrocytes? (2) How does time, both developmentally and during aging, influence the ability of neural stem cells to generate or remodel tissue homeostasis? (3) How do newborn cells remodel the existing neural circuit at local and global levels?

We believe that analysis of neurogenesis from multiple perspectives will illuminate the capacity of brain plasticity resulting from dynamic stem cell regulation. We are excited about the possibility that knowledge underlying neural development, plasticity and function generated from these studies may be leveraged for treatments of cognitive decline and brain rejuvenation.