Fields Chemical neurobiology Name Linda Hsieh-Wilson | ||
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Institutions California Institute of Technology Alma mater University of California, Berkeley Education University of California, Berkeley, Yale University | ||
Doctoral advisor Peter G. Schultz | ||
Linda Carol Hsieh-Wilson is an American chemist. She is known for her work in chemical neurobiology and is currently a professor of chemistry at the California Institute of Technology. She is also a Howard Hughes Medical Institute investigator and an adjunct professor at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles.
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Biography
Hsieh-Wilson was born in New York City, NY and received her bachelor's degree in chemistry at Yale University, where she graduated magna cum laude. She then completed her Ph.D. in 1996 at the University of California, Berkeley, where she was a National Science Foundation Fellow in the laboratory of Peter G. Schultz and studied antibody-based catalysis. She then joined the lab of Professor and Nobel Prize Laureate Paul Greengard at Rockefeller University until 2000. There she characterized the protein phosphatase and actin-binding protein spinophilin and investigated its role in dendritic spines. Hsieh-Wilson then obtained an appointment at the Department of Chemistry at the California Institute of Technology in 2000 as an assistant professor and became an investigator at the Howard Hughes Medical Institute in 2005. She then became an associate professor of chemistry in 2006 and was appointed a full professor of chemistry at the California Institute of Technology in 2010.
Overview
Hsieh-Wilson's research is at the interface between organic chemistry and neuroscience. She investigates how the post-translational addition of glycans affect the structure and function of proteins in the nervous system. Her laboratory has developed a chemoenzymatic method to tag proteins that have been appended with a dynamic form of glycosylation called O-GlcNAc. Her work with glycosaminoglycan microarrays has significantly advanced an understanding of specific sulfated glycosaminoglycans in neuronal communication, learning, and memory as well as advanced the field of chemical biology. She has demonstrated how fucosylation can modulate neurite growth and neuronal morphology.
O-GlcNAc Glycosylation
Hsieh-Wilson and her colleagues have found that the covalent-modifications of intercellular proteins by O-linked-N-acetylglucosamine (O-GlcNAc) within the mammalian nervous system have a large role in the regulation of gene expression, neuronal signaling, and synaptic plasticity. This post-translational modification, has been analysed in the rat brain using a novel chemoenzymatic strategy wherein O-GlcNAc modified proteins are selectively labeled with flourecent or biotin tags. This technique developed by Hsieh-Wilson and her lab has revealed over 200 O-GlcNAc modified proteins within the mammilian brain and such modifications have been shown to activate transcriptional function of proteins, regulate cancer metabolism, regulate gene expression and memory formation, and carry out many other tasks in the brain and beyond.
Glycosaminoglycans
Glycosaminoglycans are heterogeneously sulfated oligosaccharides that are very important in nervous system development, spinal cord injury, inflammation and cancer metastasis. Hsieh-Wilson's research on this subject implicates the specific sulfation sequence of glycosaminoglycans as a way to modulate biological function. Specifically, her work with chondroitin sulfate (CS) and heparan sulfate (HS), the two most common glycosaminoglycans in the nervous system, has shown that this "sulfation code" functions as a molecular recognition element for growth factors and modulates neuronal growth, indicating that these specific sulfated glycosaminoglycans play a major role in neuronal communication, learning, and memory. Additionally, Hsieh-Wilson has ellucidated the role of this sulfation in glycosaminoglycan-protein interaction using a carbohydrate microarray-based approach developed in her lab.
Notable papers
The Web of Science lists 51 publications in peer-reviewed scientific journals that have been cited over 1200 times, leading to an h-index of 21. Her three most cited papers (>90 times) are:
- Yan Z, Hsieh-Wilson L, Feng J, Tomizawa K, Allen PB, Fienberg AA, Nairn AC, Greengard P (January 1999). "Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin". Nature Neuroscience. 2 (1): 13–7. PMID 10195174. doi:10.1038/4516.
- Khidekel N, Ficarro SB, Peters EC, Hsieh-Wilson LC (September 2004). "Exploring the O-GlcNAc proteome: direct identification of O-GlcNAc-modified proteins from the brain". Proceedings of the National Academy of Sciences of the United States of America. 101 (36): 13132–7. PMC 516536 . PMID 15340146. doi:10.1073/pnas.0403471101. Retrieved 2011-07-16.
- Gama CI, Tully SE, Sotogaku N, Clark PM, Rawat M, Vaidehi N, Goddard WA, Nishi A, Hsieh-Wilson LC (September 2006). "Sulfation patterns of glycosaminoglycans encode molecular recognition and activity". Nature Chemical Biology. 2 (9): 467–73. PMID 16878128. doi:10.1038/nchembio810.