Linda Hsieh-Wilson
California Institute of Technology
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Primary Section: 14, Chemistry Secondary Section: 21, Biochemistry Membership Type:
Member
(elected 2022)
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Biosketch
Linda Hsieh-Wilson is a chemist known for her work on understanding the structure and function of carbohydrates in the nervous system. Her studies have revealed critical roles for carbohydrates and protein glycosylation in fundamental processes ranging from cellular metabolism to memory storage. Hsieh-Wilson was born in New York City and obtained her B.S. degree magna cum laude in chemistry from Yale University in 1990. She received her Ph.D. in chemistry from the University of California at Berkeley, where she was a National Science Foundation predoctoral fellow with Peter Schultz. In 1996, she moved to the Rockefeller University to study neurobiology as a Damon Runyon-Walter Winchell postdoctoral fellow with Paul Greegnard. Hsieh-Wilson joined the faculty at the California Institute of Technology in 2000. She has been an Investigator of the Howard Hughes Medical Institute, Arthur and Marian Hanisch Memorial Professor of Chemistry, and is currently the Milton and Rosalind Chang Professor of Chemistry at the California Institute of Technology. She is a member of the American Academy of Arts and Sciences and the National Academy of Sciences.
Research Interests
Linda Hsieh-Wilson's laboratory seeks to understand fundamental biological processes such as neuroplasticity and disease, with a focus on the roles of carbohydrates and protein glycosylation. Her group uses organic chemistry in combination with biochemistry, cell biology, and neurobiology to develop new approaches to interrogate carbohydrates and uncover their diverse functions. A major focus of the laboratory has been the development of efficient methods to synthesize defined oligosaccharides and glycan mimetics. Using these molecules, her lab has found that specific sulfated structures on chondroitin sulfate glycosaminoglycans regulate neuroplasticity by modulating signaling pathways important for axon regeneration after central nervous system injury, and blocking these structures can stimulate neuronal repair. The group has also developed technologies for the detection, imaging, and quantification of protein glycosylation, specifically O-linked N-acetylglucosylation (O-GlcNAcylation) and fucosylation. These technologies have enabled the discovery of hundreds of new glycoproteins and suggest expanded roles for carbohydrates in biology and disease. For instance, the lab discovered that dynamic, site-specific glycosylation of the transcription factor cAMP-response element binding protein (CREB) regulates neuronal gene expression, axonal and dendritic growth, and long-term memory formation.
O-GlcNAcylation also inhibits glycolysis in cancer cells by modifying phosphofructokinase-1 (PFK1), which results in increased flux through metabolic pathways important for tumor cell growth and survival. Thus, through the study of complex carbohydrates, the Hsieh-Wilson lab identifies molecular mechanisms underlying important biological processes, thereby opening up new therapeutic opportunities.
