MIT Professor Xiao Wang Leads Breakthrough Research in RNA with Innovative Imaging Techniques

Many academic institutions view broad research proposals with caution, often finding them too ambitious or vague. However, when MIT professor Xiao Wang submitted her proposal to study the life cycle of RNA in cells and its impact on development and disease, she found a receptive audience at the prestigious institution.

Embracing Bold Ideas

At MIT, Wang encountered a supportive atmosphere, where her colleagues encouraged her to expand on her original vision. “What I’m doing now is even broader than what I initially proposed,” she says, highlighting the collaborative environment that fosters innovative thinking.

With joint appointments in MIT’s Department of Chemistry and the Broad Institute of MIT and Harvard, Wang has access to a diverse network of expertise. “The joint position between MIT Chemistry and the Broad Institute was very attractive to me because I was trained as a chemist, and I would like to teach and recruit students from chemistry. But meanwhile, I also wanted to get exposure to biomedical topics and have collaborators outside chemistry,” she explains.

Developing RNA Imaging Tools

Wang’s research focuses on developing advanced tools to map RNA within cells, offering insights into how cells regulate their functions and how this control can malfunction in diseases, particularly in the brain.

One of her key contributions is the STARmap technique, which identifies the locations of different types of RNA within a single cell. This method involves crosslinking RNA within the tissue, washing it with fluorescent probes, and imaging the results to reveal the locations of thousands of RNA sequences simultaneously.

“I was leveraging my background in the chemistry of RNA to develop this RNA-centered brain mapping technology, which allows you to use RNA expression profiles to define brain cell types and also visualize their spatial architecture,” Wang says.

Expanding STARmap’s Capabilities

Wang and her team are extending the use of the STARmap technique to uncover how specific cell types regulate their RNA lifecycles and how these processes influence their function and development. They are also working to advance RNA labeling techniques to detect RNA translation at ribosomes or the rate at which mRNA degrades.

One tool, RIBOmap, identifies the locations of mRNA molecules being translated at ribosomes. Another quantifies how quickly mRNA decays after transcription.

“We are trying to develop a toolkit that will let us visualize every step of the RNA life cycle inside cells and tissues,” Wang says. “These are newer generations of tool development centered around these RNA biological questions.”

Applications in Disease Research

Wang’s work has significant implications for understanding neurological disorders such as Alzheimer’s disease and schizophrenia. Her team used an adapted version of STARmap to investigate changes in microglia cells as amyloid-beta plaques form in the brain.

By mapping the RNA expression profiles of these cells, they discovered how microglia become more inflammatory in Alzheimer’s disease, offering new insights into disease mechanisms. Wang’s lab is also exploring RNA translation in conditions like schizophrenia, aiming to identify key differences in protein production that may underpin these disorders.

“The reason we think there will be a lot of interesting biology to discover is because the formation of neural circuits is through synapses, and synapse formation and learning and memory are strongly associated with localized RNA translation, which involves multiple steps including RNA transport and recycling,” she says.

Enhancing mRNA Therapeutics

Beyond basic research, Wang’s work has practical applications in the development of mRNA vaccines and therapies. By modifying RNA’s chemical features or topological structure, she aims to enhance the efficiency and effectiveness of these treatments.

Her collaborative approach brings together chemists, biologists, computer scientists, and neuroscientists in search of solutions to complex biological questions. “There is a really innovative culture and environment here, so the students are not scared by taking on something that might sound weird or unrealistic,” Wang emphasizes.

The Journey to MIT

Xiao Wang’s path to MIT began in middle school when she participated in China’s National Olympiad in math and chemistry. Winning a gold medal in chemistry sparked her interest in science, setting her on a course toward a career in research.

After earning a degree in chemistry and molecular engineering from Peking University, Wang pursued her graduate studies at the University of Chicago, where she became fascinated by RNA modifications and their impact on protein translation.

Her work has since earned her prestigious positions at top institutions, including MIT and Stanford University. At MIT, she has continued to push the boundaries of RNA research, expanding our understanding of this vital cellular process.

Conclusion

Xiao Wang’s journey to MIT and her groundbreaking research in RNA imaging exemplifies the power of a collaborative, innovative approach to scientific inquiry. Her work not only advances our understanding of cellular biology but also has significant implications for disease research and the development of mRNA-based therapies.

As Wang continues to push the frontiers of RNA research, her contributions to science underscore the importance of embracing bold ideas and fostering a supportive research environment.

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