2024 NIHF Inductee Xiaowei Zhuang: Driven by Curiosity

Each year, the National Inventors Hall of Fame^® inducts a new class of creators and innovators who have improved our lives and advanced our society in myriad ways. One of the 15 visionaries who make up our 2024 Inductee class is Xiaowei Zhuang, a pioneer in super-resolution imaging, making possible new discoveries in biological systems and processes.

Read on to learn more about Zhuang’s inspiring work and ongoing scientific impact.

Freedom in Discovery

Zhuang was born Jan. 21, 1972, in Rugao, Jiangsu, China. In an interview with the National Inventors Hall of Fame, she explained that her mother, a professor in mechanical engineering, and her father, a professor in fluid dynamics, gave her “a lot of freedom” during her childhood. She grew up reading historical novels, including some that were quite advanced for her age. Zhuang believes her early reading habits helped her to build a strong ability to focus, which would continue to benefit her throughout her education and career.

In 1991, Zhuang graduated from the University of Science and Technology of China with her bachelor’s degree in physics, and then she came to the U.S. for her graduate studies at the University of California, Berkeley, where she earned her doctorate in physics in 1996. She completed a Chodorow Postdoctoral Fellowship at Stanford University in 2001 and has been with Harvard University since then. She currently serves as the David B. Arnold Professor of Science, as well as an investigator of the Howard Hughes Medical Institute since 2005.

“Being a professor [...] gives me 100% freedom to do whatever research I'm interested in doing,” Zhuang said. “So I make discoveries in a way that is entirely driven by my curiosity and interest, and of course, the curiosity and interest of my lab members. The freedom of making discoveries and teaching the next generations — these are things I feel I wouldn't want to trade for anything else.”

Overcoming Limits

Zhuang’s curiosity and creativity led to a breakthrough in 2006 — a new method called stochastic optical reconstruction microscopy, or STORM.

Prior to Zhuang’s work, the diffraction limit of light microscopy had prevented researchers from using light to differentiate between objects separated by 200 nanometers or less. “If you think about biological molecules like proteins, they're usually a few nanometers in size and that is two orders of magnitude smaller than the diffraction limit of resolution. Biological structures that are made of these molecules look very blurry under a light microscope,” explained Zhuang. “So if you could break that limit and get to molecular scale resolution, all of a sudden a lot of the structures inside cells will look much crisper. You could start to peek into the interactions between molecules, and that could help you understand the molecular mechanism of some of the biological functions better.”

With STORM, researchers could do just that. They could look inside cells and see how molecules interact and function with much greater clarity and much more detail.

STORM produces ultra-high-resolution images of structures that are 10,000 times smaller than the width of a strand of human hair. Using this new method, Zhuang and her colleagues discovered novel cellular structures, such as a periodic membrane skeleton in neurons that consists of rings of a protein called actin, evenly spaced and connected by another protein called spectrin.

In 2009, STORM was licensed to Nikon Corp., which introduced its N-STORM microscope in 2010. STORM is now one of the most widely used methods of super-resolution imaging. “The more people who can use our methods to make discoveries, the better,” said Zhuang. “We want to enable others to make discoveries.”

Advancing Life Sciences

STORM is not the only revolutionary technology Zhuang has developed. In 2015, she published a new genome-scale imaging method. Multiplexed error-robust fluorescence in situ hybridization, or MERFISH, allows scientists to measure and map the RNAs of thousands of genes in individual cells, identify unknown types of cells and determine the spatial organization of different types of cells in complex biological tissue, such as the brain.

MERFISH is a key technology for the Human Cell Atlas initiative, which is a global effort to identify all cell types in the human body and to map their spatial organization in order to better understand biology and disease. In 2019, Zhuang co-founded Vizgen Inc. to commercialize MERFISH, making it widely accessible to scientists and researchers to apply to their efforts in advancing medicine and life sciences.

Zhuang’s many honors include the 2018 Heineken Prize for Biochemistry and Biophysics, the 2019 Breakthrough Prize in Life Sciences, the 2019 National Academy of Sciences Award for Scientific Discovery, the 2020 Vilcek Prize in Biomedical Science and the 2023 Dreyfus Prize in Chemical Sciences. She holds 14 U.S. patents.

Meet More of Our Extraordinary 2024 Inductees

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