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Biological Chemistry

Arthur C. Cope Scholar Awards

by Kenneth Moore
February 25, 2008 | APPEARED IN VOLUME 86, ISSUE 8

Credit: Courtesy of Hsieh-Wilson
Credit: Courtesy of Hsieh-Wilson

Linda C. Hsieh-Wilson, associate professor of chemistry and Howard Hughes Medical Institute investigator at California Institute of Technology, is being honored for her pioneering work in biological chemistry characterizing complex carbohydrates and glycoproteins in the brain and exploring their roles in neurobiology. By focusing on carbohydrates involved in neural processes, one of her colleagues believes, Hsieh-Wilson has "developed remarkably productive and exciting programs in neurochemistry and glycobiology."

Hsieh-Wilson centers her research on understanding the structure and function of carbohydrates and how they interact with processes in the brain. One of the focuses of her research is O-GlcNAc glycosylation, a modification to intracellular proteins that has implications for nutrient sensing, proteasomal degradation, and gene silencing. Her addition of a ketone moiety to O-GlcNAc proteins has allowed enrichment, detection, and analysis by mass spectrometry of glycosylated proteins that had previously eluded study. Hsieh-Wilson's work has revealed roles for protein glycosylation in regulating key processes in the brain, such as transcription and nerve cell growth. Her research increases the fundamental understanding of how carbohydrates encode biological information and contribute to basic processes such as gene regulation and neuronal communication, she says.

Her unique approach combining organic chemistry and neurobiology has potential implications for understanding and treating cognitive disorders, neurodegenerative diseases, and spinal cord injury. Her work "illustrates the potential for organic chemistry to provide a perspective and a set of tools that complement biochemical and genetic approaches to understand highly interdisciplinary fields such as molecular neuroscience," Hsieh-Wilson adds.

Her colleagues call her "fearless" in her pursuit of resources necessary for her science, and Hsieh-Wilson encourages others "not to be intimidated to tackle challenging questions."

After taking an undergraduate organic chemistry class with Harry H. Wasserman at Yale University, "I was inspired to become an organic chemist," Hsieh-Wilson says. "I loved trying to understand the principles of chemical reactivity and building new structures." In 1990, she graduated magna cum laude with a bachelor's in chemistry from Yale. After completing a Ph.D. in organic chemistry at the University of California, Berkeley, she "was looking for a new challenge-an area that was relatively uncharted territory and where chemistry could make an impact," she says. "The thought of trying to understand the intricacies of the brain at a molecular level was very exciting to me."

After her studies, she spent four years as a postdoc at Rockefeller University, in New York City, studying the role of phosphorylation in regulating a protein phosphatase-1 binding protein. After the postdoc, Hsieh-Wilson became an assistant professor of chemistry, and in 2006 an associate professor, at Caltech.

Others have recognized Hsieh-Wilson's fearless research program, granting her accolades such as the 2006 Eli Lilly Award in Biological Chemistry, the 2003 Alfred P. Sloan Research Fellow, and the 2001 Arnold & Mabel Beckman Foundation Young Investigator. Hsieh-Wilson has published 36 articles, and in her spare time she enjoys exploration through running, traveling, and going to museums, theaters, and concerts.



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