Dong Yan: Molecular Players in Brain Development, Aging

Dong Yan

Dong Yan in his Duke lab, where he is studying molecular pathways critical in development and aging. Photo by Jared Lazarus/Duke University Photography

As biology major in college in northern China, Dong Yan had a somewhat disappointing first research experience. He joined a lab that classified mosquitos with visions of him trekking around a mountain and a lake for three months collecting insects.

But after he started, Yan learned that the job of an undergraduate in that lab was to stay inside and classify mosquitos by looking at their body shapes. “It sounds very boring, I know. It was very boring,” he said, with an unexpectedly warm and musical-sounding laugh.

Fortunately, Yan had a better taste of science at graduate school and beyond, even without fieldwork.

The new assistant professor of molecular genetics and microbiology in the Duke School of Medicine moved into a newly renovated laboratory space in the Clinical and Research Laboratory building at Duke.

“It’s a very challenging and exciting time for me,” said Yan, 35, who is also a member of the Duke Institute for Brain Sciences.

Using the 1-mm-long transparent worm Caenorhabditis elegans as a model, Yan studies how neuronal connections, called synapses, are first formed and how they can recover from degeneration similar to what happens after a car accident or even with normal aging.

Although it might seem like development and aging are two separate lines of research, it turns out that some of the molecules important for early brain development are also employed by cells recovering from injury, Yan's research has shown.  

“It makes sense because there are tons of proteins required for neurodevelopment that the animal has to code for,” Yan said. “If these proteins aren’t reused, it would be a waste.”

Yan’s questions about brain development began as a Ph.D. student in the Institute of Neuroscience at the Chinese Academy of Sciences, where he studied neural polarity. Neurons are, by nature, asymmetrical. Yan wanted to know how one end of a neuron became endowed with many dendrites, the spiny branches that receive signals from other neurons, while the other end of a neuron grows a single axon, a long process that transmits signals.

Using cells maintained in a petri dish, Yan’s experiments uncovered a molecular pathway that’s essential for the polarity of neurons. When the pathway was blocked, the neuron-to-be formed multiple axons instead of just one.

During Yan’s dissertation defense, a committee member asked if the same pathway was important in a living animal, but Yan didn’t know. So, for his postdoc studying  neural development with Yishi Jin at the University of California, San Diego, Yan decided to take his questions to an organism that was easy to manipulate, and created genetic mutant C. elegans worms.

Yan’s work in San Diego focused on DLK-1, a protein that controls synapse formation in baby worms. When he noticed that levels of this protein were high even after worms reached adulthood, he wondered whether it could play a role in regeneration, which was being studied by some of the other members of Jin’s lab.

“I was just curious whether DLK-1 had a function in adult worms. I decided to give it a try,” Yan said.  He deleted the protein from adult worms, finding that, amazingly, the worms were unable to regenerate axons after injury. The group published their results in the journal Cell in 2009 and in Neuron in 2012.

DLK-1 is a molecule that works by controlling the activation of other crucial proteins in specific parts of a neuron. Since Yan’s initial finding, other groups have shown that DLK-1 is also important for axon regeneration in the fly and the mouse.

“That says a lot about the reason we study C. elegans,” Yan said. Worms, flies, and mammals share a lot of the same molecules involved in development and disease. Yan is still working on DLK-1, but his work aims to find other new regulators of synapse formation and axon regeneration.

Yan lives in Chapel Hill with his wife, a clinical research scientist. He gets his nature fix by hiking; his favorite place is Eno River State Park.