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Xiaoke Chen is the first recipient of the Firmenich Next Generation Fund

By Amy Adams

 

Xiaoke Chen, assistant professor of biology, is the first recipient of support from the Firmenich Next Generation Fund. His work explores how our body’s sense of self motivates behavior, for example eating when we’re hungry and getting a sweater when we’re cold.  

Chen has been trying to identify the brain circuit that motivates our behaviors in response to negative sensations such as pain, the physical effects of drug withdrawal, or social stress.  He hopes that unraveling this neural mechanism in animals will lead to ideas for novel therapies in people.

“If we figure out how this brain circuit works and how it is changed in disorders like addiction or depression it might lead to better strategies for treating those diseases,” Chen said.

The fund is provided by the Firmenich Foundation, the philanthropic arm of Firmenich, the world’s largest privately owned producer of fragrances and flavors. Antoine Firmenich, the great-grandson of the founder, is a Stanford alumnus (PhD ’94, MBA ’96).

In one set of experiments published earlier this year in Nature, Chen and his team identified a brain region that was unusually active in opiate-addicted mice.  When the team dialed down the activity of this region to more normal levels, they found the physical symptoms and the memory of opiate withdrawal were suppressed. Chen and his team also found that the same brain region mediated the mouse’s perception of other negative stimuli including pain.

Chen thinks a similar mechanism involving this brain region might be at work in depression or post traumatic stress disorder. Turning down this pathway could help people function better in their lives ­– they might still feel the stress, but they wouldn’t be incapacitated by it.

In another set of experiments published in Nature Neuroscience, Chen found that heat or cold sensation on the skin activates neurons in the spinal cord, but in different ways. The neurons acclimate to cold, only firing in response to a change in the temperature. By contrast the cells continue to fire more strongly as the heat rises.

The technique Chen uses to alter neural activity in mice, called optogenetics, can’t be used in people. However, Chen said other tools that can remotely stimulate brain regions in people might be one way of translating their work. He is also examining the molecular changes that occur in this brain region after drugs or stress, to identify potential drug targets for treating these disorders. 

Chen has been at Stanford just under four years, which is a stage when faculty often feel the need to make safe choices in order to get the kinds of results needed for major grants. This award will allow him to continue to do cutting-edge research.

“This gives me the freedom to do exploratory, high risk work,” Chen said. “It is very timely for a young investigator.”