Diane Shao (she/her), a physician-scientist at Harvard Medical School and Boston Children’s Hospital, sees it as her job to fundamentally understand why her young patients have neurodevelopmental disabilities and how they came to have them. “A lot of the patients coming to my clinic have unclear diagnoses that another clinician may not have expertise to figure out yet,” she said. “My role is to provide an answer. Why is it that they are the way that they are, and what is the genetics of them?”
To find those answers, Shao is probing unexplored depths of the developing human brain by sequencing the whole genomes of individual fetal neurons. She’s already uncovered evidence that, during fetal development, neurons can vary from each other far more than scientists originally thought. Those cell-to-cell differences might arise from copy errors as the fetus grows or as a result of certain environmental exposures.
“The really fascinating thing is they seem to correct themselves after we’re born. So, this is a new finding of a way the brain has of regulating itself, potentially. Whenever you find a new mechanism, it’s potentially a mechanism that can go wrong,” Shao said.
Investigating that mechanism might help further our understanding of where certain developmental disabilities come from — and potentially how to correct them. When Shao thinks about these scientific and clinical pursuits, she practically vibrates with enthusiasm. “That’s the ‘unknown unknowns’ of looking into the future,” she said. “Being part of a vision shaping the next decades in my life.”
Single-cell genomic analyses are still “very early in terms of what we can understand from it,” she said. “It means I can predict some aspects of the future, but a large portion of the implications, that I and no one else have imagined yet.” And, as a lifelong overachiever who has organized humanitarian trips and statewide math competitions, and whose undergraduate research eventually led to a biotech that sold for $1.4 billion dollars, Shao plans to do even more. She also co-founded Legacy Venture Capital in 2024, and she wants to take insights from fundamental research from the lab bench and into the world.
—Angus Chen
