Linda Hsieh-Wilson Explained

Linda Carol Hsieh-Wilson
Fields:Chemical neurobiology
Workplaces:California Institute of Technology
Alma Mater:University of California, Berkeley
Doctoral Advisor:Peter 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

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

Overview

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

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

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

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:

  1. Yan Z, Hsieh-Wilson L, Feng J, Tomizawa K, Allen PB, Fienberg AA, Nairn AC, Greengard P . Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin . . 2 . 1 . 13–7 . January 1999 . 10195174 . 10.1038/4516 . 2534174 .
  2. Khidekel N, Ficarro SB, Peters EC, Hsieh-Wilson LC . Exploring the O-GlcNAc proteome: direct identification of O-GlcNAc-modified proteins from the brain . . 101 . 36 . 13132–7 . September 2004 . 15340146 . 516536 . 10.1073/pnas.0403471101 . 2004PNAS..10113132K . free .
  3. Gama CI, Tully SE, Sotogaku N, Clark PM, Rawat M, Vaidehi N, Goddard WA, Nishi A, Hsieh-Wilson LC . Sulfation patterns of glycosaminoglycans encode molecular recognition and activity . . 2 . 9 . 467–73 . September 2006 . 16878128 . 10.1038/nchembio810 . 1229340 .

Awards and honors

Notes and References

  1. Web site: Linda Carol Hsieh-Wilson, California Institute of Technology: Learning and memory, Memory and motor control, Neurobiology • Expertise Finder Network. Finder. Expertise. network.expertisefinder.com. 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 . 39251. 8643580. 10.1073/pnas.93.11.5363. 1996PNAS...93.5363H. free.
  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. 10.1021/bi982900m . 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. 10.1385/NMM:2:1:61 . 12230305. 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. 10.1074/jbc.M205754200 . 12417592. 11557256. free.
  6. Web site: Linda C. Hsieh-Wilson www.cce.caltech.edu. www.cce.caltech.edu. en. 2017-05-02.
  7. Web site: HHMI Scientist Abstract: Linda C. Hsieh-Wilson, Ph.D. . Howard Hughes Medical Institute . 2011-07-16.
  8. 10.1038/nchembio881 . Probing the dynamics of O-GlcNAc glycosylation in the brain using quantitative proteomics . 2007 . Khidekel . Nelly . Ficarro . Scott B . Clark . Peter M . Bryan . Marian C . Swaney . Danielle L . Rexach . Jessica E . Sun . Yi E . Coon . Joshua J . Peters . Eric C . 8. . 3 . 6 . 339–348 . 17496889.
  9. 10.1038/nchembio810 . Sulfation patterns of glycosaminoglycans encode molecular recognition and activity . 2006 . Gama . Cristal I . Tully . Sarah E . Sotogaku . Naoki . Clark . Peter M . Rawat . Manish . Vaidehi . Nagarajan . Goddard . William A . Nishi . Akinori . Hsieh-Wilson . Linda C . 8. Nature Chemical Biology . 2 . 9 . 467–473 . 16878128. 1229340 .
  10. 10.1126/stke.3172006tw472 . Sweet Memories of Synapsins? . 2006 . Science's STKE . 2006 . 317 . tw472. 220299653 .
  11. Khidekel . Nelly . Ficarro . Scott B. . Peters . Eric C. . Hsieh-Wilson . Linda C. . Exploring the O-GlcNAc proteome: Direct identification of O-GlcNAc-modified proteins from the brain . Proceedings of the National Academy of Sciences . 7 September 2004 . 101 . 36 . 13132–13137 . 10.1073/pnas.0403471101 . 15340146 . 516536 . 2004PNAS..10113132K . free .
  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|date=January 2022}}
  13. Hsieh-Wilson. Linda. 2013-04-01. O-GlcNAc Signaling Regulates Cancer Metabolism . The FASEB Journal. en. 27. 1 Supplement. 452.2. 10.1096/fasebj.27.1_supplement.452.2 . free.
  14. http://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=DaisyOneClickSearch&qid=11&SID=1AMO2etzAYAIFJZoUSG&page=1&doc=21{{dead link|date=January 2022}}
  15. Sulfation patterns of glycosaminoglycans encode molecular recognition and activity. 10.1038/nchembio810. 2006. Gama. Cristal I.. Tully. Sarah E.. Sotogaku. Naoki. Clark. Peter M.. Rawat. Manish. Vaidehi. Nagarajan. Goddard. William A.. Nishi. Akinori. Hsieh-Wilson. Linda C.. Nature Chemical Biology. 2. 9. 467–473. 16878128. 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. Journal of the American Chemical Society. 126. 25. 7736–7737. 10.1021/ja0484045. 15212495. 0002-7863.
  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. 10.1016/j.chembiol.2006.12.009. 17317573. free.
  18. Web site: Web of Science . 2011 . 2011-07-16.
  19. Web site: Linda C. Hsieh-Wilson . Arnold and Mabel Beckman Foundation . 1 August 2018.
  20. Web site: Arthur C. Cope Scholar Awards . . 2011-07-16 . dead . https://web.archive.org/web/20110811230542/http://portal.acs.org/portal/acs/corg/content?_nfpb=true&_pageLabel=PP_ARTICLEMAIN&node_id=1319&content_id=CTP_004496&use_sec=true&sec_url_var=region1 . 2011-08-11 .
  21. Web site: Top neuroscientists receive awards from IU's Gill Center . Indiana University . IU News Room . 2019-09-15.

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