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Roger Zou

Johns Hopkins University

Growing up, Roger Zou always had more questions than biology textbooks had answers. But it wasn’t until he was an undergraduate at Duke University that he started harnessing his math and coding chops to try to answer some of them.

How exactly does a single cell build a whole fruit fly? Zou constructed algorithms that let developmental biologists working with new live imaging technologies track individual cells as they divided and became unique tissues.

Now, as an M.D./Ph.D. student in the lab of Johns Hopkins physicist Taekjip Ha, who studies the mechanics of single molecules, Zou has zeroed in on one particularly famous duo: CRISPR-Cas9.

In 2021, he and his colleagues helped the field of genome editing tackle a longstanding hurdle: controlling exactly when and where CRISPR-Cas9 makes its cuts. The programmable DNA-slicing system can sometimes miss its mark, causing off-target effects or traveling beyond the tissues it is supposed to treat.

To rein in CRISPR, researchers have tried to make light-activated Cas9 proteins. Using chemically caged guide RNAs, Zou’s team developed a much more precise optical control knob that allows researchers to put CRISPR to work in particular cell types or at specific points in development. That’s making it easier to study how cells repair the DNA damage done by CRISPR, a knowledge gap that has held up more ambitious genome editing targets.

Zou and his colleagues also discovered that their system could identify off-target effects in living organisms. Existing methods are mostly limited to test tubes, so more clinically relevant techniques are in high demand.

That work is not yet published, but it might be Zou’s last, at least for a little while. The fourth-year medical student doesn’t expect to return to the bench until after he completes residency. “It’s going to be hard to leave the subject completely,” Zou said. “I have a lot of optimism for the potential of CRISPR systems to advance science and medicine.”

Born in Shanghai, Zou grew up aspiring to become a scientist like his father — a prominent prion researcher. In 2012, Zou co-captained his high school Science Olympiad team to a national championship. When he’s not working, studying, or seeing patients, Zou heads to the water — either to fish or paddle his kayak. “Probably my favorite thing about going to medical school in Baltimore is access to Chesapeake Bay,” he said. “There’s so much there to explore.”

— Megan Molteni