The Brain’s Blueprint Maker
In her lab at Duke University School of Medicine, amid trays of lab-grown brain tissue, developmental neurobiologist Debra Silver, PhD, is trying to solve some of the biggest mysteries in neuroscience: How the brain develops, why it occasionally misfires, and what lifted human cognition beyond that of our closest relatives.
Most labs would consider any one of those issues a lifetime’s work. Silver views them as inseparable.
“Sometimes people will say, ‘You’re studying very different questions,’” said Silver, who is a professor in the departments of cell biology and molecular genetics and microbiology and a Duke Science and Technology Scholar. “I don’t think of it that way at all.”
Essentially, Silver wants to know what makes a human brain a human brain. She approaches that from three directions: mapping how a healthy brain forms long before birth, investigating the causes of brain disorders such as autism spectrum disorder, and discovering how human brains evolved.
That wide-angled approach has turned Silver into one of the field’s most visible and decorated scientists.
Her lab’s discoveries have been published in top academic journals, featured in National Geographic and on NPR, and in 2024 she received the Javits Award from the National Institute of Neurological Disorders and Stroke, an honor reserved for scientists with “superior competence and outstanding productivity.”
Early architects of the brain
Silver’s research centers on an unassuming group of cells with outsize influence: neural progenitors, the fetal-stage cells that generate neurons and glia and help organize the brain’s basic structure.
“Our lab is investigating fundamental questions about how our brain develops,” Silver said. “We’re trying to understand how billions of diverse and complex cells in our brains are made at the right time and right place.”
Her team has shown that neural progenitors aren’t just factories turning out new cells. They communicate with their neighbors, shaping how newborn neurons behave and where they migrate.
“Neural progenitors are even more important than had previously been appreciated,” she said. “They are not just making cells but influencing them once they are made.”
Mapping out the normal route of development is fascinating to Silver in its own right, but she also hopes it will highlight places where wrong turns lead to conditions such as microcephaly (an unusually small brain), intellectual disability, autism, or rare neurodevelopmental diseases.
During the rapid growth of a fetal brain, small missteps can snowball. “You can end up with a brain that doesn’t have enough neurons, or it has enough neurons, but they are the wrong type, or they are the right type but in the wrong place.”
When development detours
One disease she studies is called DDX3X syndrome, a genetic disorder linked to intellectual disability and autism. Through the DDX3X Foundation, Silver and members of her lab met families affected by the condition.
“I’m a basic scientist,” she said. “But meeting those families changed how we think about our work. It gave our research a face, if you will, and made the science feel more urgent.”
Her students feel that drive. Federica Mosti, a doctoral researcher who joined the lab in 2021, describes the environment as “supportive, inclusive and collaborative.” Silver, she said, “wants us to be successful in our careers.”
That dedication to mentorship also caught the attention of Scott Soderling, PhD, chair of the Department of Cell Biology, who appointed her vice chair of faculty development.
How humans diverged from chimps
Silver’s lab is also probing evolution’s imprint on the brain by studying regulatory DNA, the molecular switches that turn genes on and off.
In both animal models and human organoids, the team has shown that several human versions of these regulatory DNA drive larger or more complex brain tissue than the chimp versions.
The findings hint at a constellation of small ancient genetic shifts ¸— perhaps thousands — that helped shape the human cortex.
Far from daunted, Silver is invigorated.
“This is such an exciting time in science,” she said. “We have all these really cool tools for manipulating genomes and for imaging. It’s making possible things we couldn’t dream of doing years ago.”
Soderling says that sense of possibility defines Silver’s career. Away from the lab, she’s an avid scuba diver, drawn to the same combination of precision and adventure that powers her science.
“To be a scuba diver, you have to be precise and pay attention to detail,” he said. “It takes training and a sense of adventure. That perfectly sums up Debby in the lab.”
Mary-Russell Roberson is a freelance writer living in Durham.
Eamon Queeney is assistant director of multimedia & creative in the Office Strategic Communications at the Duke University School of Medicine.