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Linda Hsieh-Wilson

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Linda Carol Hsieh-Wilson
Alma materUniversity of California, Berkeley
Scientific career
FieldsChemical neurobiology
InstitutionsCalifornia Institute of Technology
Doctoral advisorPeter G. Schultz

Linda Carol Hsieh-Wilson is an American chemist and the Milton and Rosalind Chang Professor of Chemistry at the California Institute of Technology. She is known for her work in chemical neurobiology 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. She is a member of the American Academy of Arts and Sciences and was elected to the National Academy of Sciences in 2022.

Biography

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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.[1][2] She then joined the lab of Professor and Nobel Prize Laureate Paul Greengard at Rockefeller University, where she characterized the protein phosphatase and actin-binding protein spinophilin[3] and investigated its role in dendritic spines.[4][5] Hsieh-Wilson obtained an appointment in the Division of Chemistry and Chemical Engineering 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 was appointed to associate professor of chemistry in 2006 and full professor of chemistry at the California Institute of Technology in 2010.[6]

Research interests

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Overview

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Hsieh-Wilson's research is at the interface between organic chemistry and neuroscience.[7] 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.[8] 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.[9] She has demonstrated how fucosylation can modulate neurite growth and neuronal morphology.[10]

O-GlcNAc Glycosylation

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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.[11] 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 fluorescent or biotin tags. This technique developed by Hsieh-Wilson and her lab has revealed over 200 O-GlcNAc modified proteins within the mammalian brain and such modifications have been shown to activate transcriptional function of proteins,[12] regulate cancer metabolism,[13] regulate gene expression and memory formation,[14] and carry out many other tasks in the brain and beyond.

Glycosaminoglycans

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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,[15][16] indicating that these specific sulfated glycosaminoglycans play a major role in neuronal communication, learning, and memory. Additionally, Hsieh-Wilson has elucidated the role of this sulfation in glycosaminoglycan-protein interaction using a carbohydrate microarray-based approach developed in her lab.[17]

Notable papers

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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.[18] Her three most cited papers (>90 times) are:[18]

  1. 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. doi:10.1038/4516. PMID 10195174. S2CID 2534174.
  2. 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. Bibcode:2004PNAS..10113132K. doi:10.1073/pnas.0403471101. PMC 516536. PMID 15340146.
  3. 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" (PDF). Nature Chemical Biology. 2 (9): 467–73. doi:10.1038/nchembio810. PMID 16878128. S2CID 1229340.

Awards and honors

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References

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  1. ^ Finder, Expertise. "Linda Carol Hsieh-Wilson, California Institute of Technology: Learning and memory, Memory and motor control, Neurobiology • Expertise Finder Network". network.expertisefinder.com. Retrieved 2017-05-02.
  2. ^ Hsieh-Wilson, L. C.; Schultz, P. G.; Stevens, R. C. (1996-05-28). "Insights into antibody catalysis: structure of an oxygenation catalyst at 1.9-angstrom resolution". Proceedings of the National Academy of Sciences of the United States of America. 93 (11): 5363–5367. Bibcode:1996PNAS...93.5363H. doi:10.1073/pnas.93.11.5363. PMC 39251. PMID 8643580.
  3. ^ Hsieh-Wilson, L. C.; Allen, P. B.; Watanabe, T.; Nairn, A. C.; Greengard, P. (1999-04-06). "Characterization of the neuronal targeting protein spinophilin and its interactions with protein phosphatase-1". Biochemistry. 38 (14): 4365–4373. doi:10.1021/bi982900m. PMID 10194355.
  4. ^ Grossman, Stacie D.; Hsieh-Wilson, Linda C.; Allen, Patrick B.; Nairn, Angus C.; Greengard, Paul (2002-01-01). "The actin-binding domain of spinophilin is necessary and sufficient for targeting to dendritic spines". Neuromolecular Medicine. 2 (1): 61–69. doi:10.1385/NMM:2:1:61. PMID 12230305. S2CID 21825701.
  5. ^ Hsieh-Wilson, Linda C.; Benfenati, Fabio; Snyder, Gretchen L.; Allen, Patrick B.; Nairn, Angus C.; Greengard, Paul (2003-01-10). "Phosphorylation of spinophilin modulates its interaction with actin filaments". The Journal of Biological Chemistry. 278 (2): 1186–1194. doi:10.1074/jbc.M205754200. PMID 12417592. S2CID 11557256.
  6. ^ "Linda C. Hsieh-Wilson | www.cce.caltech.edu". www.cce.caltech.edu. Retrieved 2017-05-02.
  7. ^ "HHMI Scientist Abstract: Linda C. Hsieh-Wilson, Ph.D." Howard Hughes Medical Institute. Retrieved 2011-07-16.
  8. ^ Khidekel, Nelly; Ficarro, Scott B; Clark, Peter M; Bryan, Marian C; Swaney, Danielle L; Rexach, Jessica E; Sun, Yi E; Coon, Joshua J; et al. (2007). "Probing the dynamics of O-GlcNAc glycosylation in the brain using quantitative proteomics" (PDF). Nature Chemical Biology. 3 (6): 339–348. doi:10.1038/nchembio881. PMID 17496889.
  9. ^ Gama, Cristal I; Tully, Sarah E; Sotogaku, Naoki; Clark, Peter M; Rawat, Manish; Vaidehi, Nagarajan; Goddard, William A; Nishi, Akinori; et al. (2006). "Sulfation patterns of glycosaminoglycans encode molecular recognition and activity" (PDF). Nature Chemical Biology. 2 (9): 467–473. doi:10.1038/nchembio810. PMID 16878128. S2CID 1229340.
  10. ^ "Sweet Memories of Synapsins?". Science's STKE. 2006 (317): tw472. 2006. doi:10.1126/stke.3172006tw472. S2CID 220299653.
  11. ^ Khidekel, Nelly; Ficarro, Scott B.; Peters, Eric C.; Hsieh-Wilson, Linda C. (7 September 2004). "Exploring the O-GlcNAc proteome: Direct identification of O-GlcNAc-modified proteins from the brain". Proceedings of the National Academy of Sciences. 101 (36): 13132–13137. Bibcode:2004PNAS..10113132K. doi:10.1073/pnas.0403471101. PMC 516536. PMID 15340146.
  12. ^ http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=DaisyOneClickSearch&qid=11&SID=1AMO2etzAYAIFJZoUSG&page=1&doc=6&cacheurlFromRightClick=no[dead link‍]
  13. ^ Hsieh-Wilson, Linda (2013-04-01). "O-GlcNAc Signaling Regulates Cancer Metabolism". The FASEB Journal. 27 (1 Supplement): 452.2. doi:10.1096/fasebj.27.1_supplement.452.2.
  14. ^ http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=DaisyOneClickSearch&qid=11&SID=1AMO2etzAYAIFJZoUSG&page=1&doc=21[dead link‍]
  15. ^ Gama, Cristal I.; Tully, Sarah E.; Sotogaku, Naoki; Clark, Peter M.; Rawat, Manish; Vaidehi, Nagarajan; Goddard, William A.; Nishi, Akinori; Hsieh-Wilson, Linda C. (2006). "Sulfation patterns of glycosaminoglycans encode molecular recognition and activity". Nature Chemical Biology. 2 (9): 467–473. doi:10.1038/nchembio810. PMID 16878128. S2CID 1229340.
  16. ^ Tully, Sarah E.; Mabon, Ross; Gama, Cristal I.; Tsai, Sherry M.; Liu, Xuewei; Hsieh-Wilson, Linda C. (2004-06-01). "A Chondroitin Sulfate Small Molecule that Stimulates Neuronal Growth" (PDF). Journal of the American Chemical Society. 126 (25): 7736–7737. doi:10.1021/ja0484045. ISSN 0002-7863. PMID 15212495.
  17. ^ Shipp, Eric L.; Hsieh-Wilson, Linda C. (2007-02-01). "Profiling the Sulfation Specificities of Glycosaminoglycan Interactions with Growth Factors and Chemotactic Proteins Using Microarrays". Chemistry & Biology. 14 (2): 195–208. doi:10.1016/j.chembiol.2006.12.009. PMID 17317573.
  18. ^ a b "Web of Science". 2011. Retrieved 2011-07-16.
  19. ^ "Linda C. Hsieh-Wilson". Arnold and Mabel Beckman Foundation. Retrieved 1 August 2018.
  20. ^ "Arthur C. Cope Scholar Awards". American Chemical Society. Archived from the original on 2011-08-11. Retrieved 2011-07-16.
  21. ^ "Top neuroscientists receive awards from IU's Gill Center". IU News Room. Indiana University. Retrieved 2019-09-15.
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