Fred H. Gage

Salk Institute for Biological Studies

Election Year: 2003
Primary Section: 28, Systems Neuroscience
Secondary Section: 24, Cellular and Molecular Neuroscience
Membership Type: Member

Research Interests

Recently I have focused the majority of my efforts at the interface of the fields of neurobiology and stem cell biology. These studies began with our discovery that FGF-2 could be used to isolate and propagate neural stem cells from the adult hippocampus. We went on to demonstrate that the isolated adult stem cells could be transplanted back to the adult brain, where they could differentiate into mature neurons in specific brain regions. These regions were found to be the same regions in which the adult brain harbors endogenous cells that give rise to neurons throughout life. My colleagues and I then demonstrated that the stem cells persist in the dentate gyrus, giving rise to new neurons throughout life, and that the rate at which new neurons are born and subsequently survive and integrate into the brain is regulated by environment and experience (for example, enrichment and exercise). Subsequently, we showed that this process of neurogenesis occurs in humans. We have been actively identifying mechanisms that regulate and control neurogenesis, both in vitro and in vivo, and most importantly, have characterized several critical elements in the cellular and molecular niche of the subgranular zone of the dentate gyrus that controls neurogenesis. This line of investigation was highlighted by the observation that adult hippocampal astrocytes induce adult hippocampus stem cells to become neurons. In a separate set of experiments combining retroviral gene targeting, confocal microscopy and single unit patch recording, we demonstrate that the neurons born in the adult brain are functional. We continue to work on the molecular mechanisms and environmental stimuli that control and regulate adult neurogenesis, as well as begin to address functional role for neurogenesis in the adult mammalian brain.

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