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Chi-Huey Wong on the Implementation of Glycan Engineering in Cancer Therapeutics

LA JOLLA, CA / ACCESSWIRE / June 6, 2019 / Glycans, or chains of sugar molecules, play a key role in many biological processes within the human body. This area of medical science has been underexplored so far, due to the lack of tools to map complex glycan structures, says Chi Huey Wong. Within a body, proteins and lipids on the surface of cells are covered with glycans. Their role is to help cells to develop and communicate with each other. The formation of these sugar chains is driven by a variety of factors, including nutrient availability and cellular metabolism, making them difficult to regulate under lab conditions.

Understanding the full picture of glycan structures in the body - the human glycome - will assist doctors in predicting risk of disease. Changes in the sugars' molecular structures are associated with presence of cancers and autoimmune diseases. The journal Glycobiology reported the link between alterations in glycosylation (when a glycan attaches to another molecule) and ovarian cancer in a pilot study. Furthermore, glycosylated proteins have been found to be overexpressed in tumor cells. Despite promising research, identifying where these "biomarkers" are and how glycans differ in patients with and without cancer remains a difficult task. In contrast to other biological processes (like the formation of proteins), glycans do not follow a known template. The challenge lies in the sheer volume and complexity in mapping these structures. Glycoscientists must catalogue the structures of each sugar chain, and identify the sites where they attach onto a protein. The Science Daily estimates that for every protein found on a cell's surface, around 70% of its area is covered in glycans.

Not only can glycan engineering improve the diagnosis of cancer, it can also develop individualized treatments. Because glycans influence the behavior of genes and proteins, they can transmit information to doctors on how a patient will likely react to certain medicines. Future breakthroughs will contribute to new cancer therapies that can target interventions based on a patient's biomarkers, according to Chi-HueyWong. Glycan engineering of antibodies through chemo-enzymaticmanipulation has identified an universal glycan to significantly improve the efficacy of antibody used in the treatment of cancer [1,2,3]. The glycan moiety on the antibody can also be further stabilized by introducing a fluorine group to the sialic acid residue to prevent its cleavage by glycosidases and thus prolong the efficacy via effector functions[3]. Vaccines, including those designed for cancers, are another area of potential innovation for glycoscience. The sugar chains act as markers for native cells, informing the immune system when foreign viruses or bacteria appear. Scientists will be able to foresee a patient's response to new vaccines by observing the reaction of glycans as the body recognizes molecular structures of specific pathogens.

Dr. Chi-Huey Wong is a distinguished researcher in the field of chemical biology. He was a Post Doctoral Fellow at Harvard University from 1982 to 1983, before teaching as a professor and chair in Chemistry for the Scripps Research Institute from 1989. Wong has received numerous awards in his field of research, including the Wolf Prize in Chemistry (2014), the American Chemical Society Arthur C. Cope Award (2012), and the F. A. Cotton Medal for Excellence in Chemical Research (2008). He also served as the Director of The Genomics Research Center in Taiwan's Academia Sinica from 2003 to 2006 and President of Academia Sinica from 2006-2016. Dr. Wong studied chemistry and biochemical sciences at Taiwan National University before receiving his PhD in organic chemistry from the Massachusetts Institute of Technology in 1982.

Chi-Huey Wong Reviews the Methods of Automation in Oligosaccharides Synthesis: https://finance.yahoo.com/news/chi-huey-wong-reviews-methods-010000727.html

Scripps Research Institute Chemist Chi-Huey Wong Wins Prestigious Wolf Prize: https://www.scripps.edu/news-and-events/press-room/2014/20140124wong.html

ChemBioChem: Chi-Huey Wong's 70th birthday - Wiley Online Library: https://onlinelibrary.wiley.com/doi/toc/10.1002/(ISSN)1439-7633.ChiHueyWong

  1. Chiu-Ping Liu, Tsung-I. Tsai, Ting Cheng, Vidya S. Shivatare, Chung-Yi Wu, Chung-Yi Wu, and Chi-Huey Wong, " Glycoengineering of antibody (Herceptin) through yeast expression and in vitro enzymatic glycosylation", Proceedings of the National Academy of Sciences, 115 (4) 720-725, (2018). (https://doi.org/10.1073/pnas.1718172115)

  2. Sachin S. Shivatare, Lin-Ya Huang, Yi-Fang Zeng, Jung-Yu Liao, Tsai-Hong You, Shi-Yun Wang, Ting Cheng, Chih-Wei Chiu, Ping Chao, Li-Tzu Chen, Tsung-I Tsai , Chiu-Chen Huang, Chung-Yi Wu , Nan-Horng Lin, and Chi-Huey Wong, "Development of glycosynthases with broad glycan specificity for the efficient glyco-remodeling of antibodies", Chem. Commun, 54, 6161-6164, (2018). (DOI: 10.1039/C8CC03384F)

  3. H.-J. Lo, L. Krasnova, S. Dey, T. Cheng, H. Liu, T.-I. Tsai, K. B. Wu, C.-Y. Wu, and C.-H. Wong, "Synthesis of sialidase-resistant oligosaccharide and antibody glycoform containing α2,6-linked 3Fax-Neu5Ac", J. Am. Chem. Soc., 141 (16), 6484-6488, (2019). ( https://www.ncbi.nlm.nih.gov/pubmed/30969765)

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Chi-Huey Wong

SOURCE: Chi-Huey Wong

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