Yuan Chuan Lee

Yuan Chuan Lee

Research Professor

141A Levi Hall
410-516-7041 |Lab 410-516-7322
yclee@jhu.edu

Research
Publications
Lab Members

Glycobiology: Glycoproteins, Glycolipids, and Cell Surface Carbohydrate Receptors

Glycobiology: Glycoproteins, Glycolipids, and Cell Surface Carbohydrate Receptors
Glycoconjugates (i.e., glycoproteins, glycolipids, etc.) are widely distributed in nature, and play diverse and important functions. We are trying to understand how carbohydrate groups in glycoconjugates are recognized in biological systems, and how they function as biological signals. Our current major interests are listed below:

1) Carbohydrate-mediated defense mechanism. Carbohydrate recognition can be used in a defense mechanism. A typical case is mannose-binding protein in human serum, which performs pre-immune defense against invading agents. An acute-phase protein, C-reactive protein, is another such defense molecule, and we are investigating its carbohydrate-binding specificity as related to its biological functions.

2) Glycopathology, i.e., how the glycoconjugates are involved in various pathogenesis and how they can be used in prevention. Among the avian species, pigeons and doves are unique in that their egg proteins contain “galabiose” (Gala(1-4)Gal) sequence. The galabiose exists in human cells as glycolipids, and is a ligand for many pathogenic microbes as well as for some microbial toxins. Pigeon egg white glycoproteins and oligosaccharides or glycopeptides inhibit microbial invasion as well as internalization of toxins.

3) Evolution of glycans in glycoproteins in avian species (AvioGlycomics). It is curious that only pigeons and doves are known to have the galabiose sequence in its N-glycans. We are examining the phylogenetically related avian eggs to gain insight to this enigma.

4) Glycoside clustering effect. Carbohydrates are the only biopolymers that can form branched structures. Hence the specific recognition of carbohydrates often involves subtle differentiation of branched structures. When spatially suitably oriented, the terminal sugar units of clustered carbohydrates, which are often the target for recognition, can manifest tremendous enhancement of binding affinity, which is termed “glycoside clustering effect”. We are investigating the origin of this effect so that it can be used in construction of effective “glyco-drugs.” We are now adopting nanotechnology to explore innovative approaches in this area. One of the practical application of this methodology is to organ specific delivery of a malaria drug, promaquine, to the liver. Liver is where Pasmodium falciparum spends the longest time. By selective delivery of the drug to liver, it is expected to combat malaria without severe side effect.

5) Glyco-nanotechnology. Nanomaterials show very interesting properties different from other materials. We are developing nanoparticles decorated with defined carbohydrates for detection of specific cells (including tumor/cancer) as well as for targeted delivery of drugs.

Recent Publications

Lee, R. T., Wang, M. H., Lin, W. J., and Lee, Y. C. (2011) New and more efficient multivalent glyco-ligands for asialoglycoprotein receptor of mammalian hepatocytes. Bioorg Med Chem, 19, 2494-500

Lee, R. T., Hsu, T. L., Huang, S. K., Hsieh, S. L., Wong, C. H., and Lee, Y. C. (2011) Survey of immune-related, mannose/fucose-binding C-type lectin receptors reveals widely divergent sugar-binding specificities. Glycobiology, 21, 512-20 PMC3055596

Zhou, Y., Kawasaki, H., Hsu, S.-C., Lee, R. T., Yao, X., Plunkett, B., Fu, J., Yang, K., Lee, Y. C., and Huang, S.-K. (2010) Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1. Nat. Med. (N. Y., NY, U. S.), 16, 1128-33

Lee, Y. C. (2010) Warfare between pathogens and hosts: the trickery of sugars. Trends Glycosci. Glycotechnol., 22, 95-106

Hsu, S. C., Chen, C. H., Tsai, S. H., Kawasaki, H., Hung, C. H., Chu, Y. T., Chang, H. W., Zhou, Y., Fu, J., Plunkett, B., Su, S. N., Vieths, S., Lee, R. T., Lee, Y. C., and Huang, S. K. (2010) Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells. J Biol Chem, 285, 7903-10 PMC2832940

Suzuki, N., Su, T. H., Wu, S. W., Yamamoto, K., Khoo, K. H., and Lee, Y. C. (2009) Structural analysis of N-glycans from gull egg white glycoproteins and egg yolk IgG. Glycobiology, 19, 693-706

Liu, J. C., Chen, W. J., Li, C. W., Mong, K. K., Tsai, P. J., Tsai, T. L., Lee, Y. C., and Chen, Y. C. (2009) Identification of Pseudomonas aeruginosa using functional magnetic nanoparticle-based affinity capture combined with MALDI MS analysis. Analyst, 134, 2087-94

Lee, Y. C. (2009) Neoglycoproteins, chemistry of. Wiley Encyclopedia of Chemical Biology, 3, 298-307

Gillmeister, M. P., Tomiya, N., Jacobia, S. J., Lee, Y. C., Gorfien, S. F., and Betenbaugh, M. J. (2009) An HPLC-MALDI MS method for N-glycan analyses using smaller size samples: Application to monitor glycan modulation by medium conditions. Glycoconjugate J., 26, 1135-49

Argayosa, A. M., and Lee, Y. C. (2009) Identification of L-fucose-binding proteins from the Nile tilapia (Oreochromis niloticus L.) serum. Fish & Shellfish Immunology, 27, 478-85

Liu, J. C., Tsai, P. J., Lee, Y. C., and Chen, Y. C. (2008) Affinity capture of uropathogenic Escherichia coli using pigeon ovalbumin-bound Fe3O4@Al2O3 magnetic nanoparticles. Anal Chem, 80, 5425-32

2007 and older

Hsu, S. C., Tsai, T. H., Kawasaki, H., Chen, C. H., Plunkett, B., Lee, R. T., Lee, Y. C., and Huang, S. K. (2007) Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice. J Allergy Clin Immunol., 119, 1522-8.

Hsu, N. Y., Yang, W. B., Wong, C. H., Lee, Y. C., Lee, R. T., Wang, Y. S., and Chen, C. H. (2007) Matrix-assisted laser desorption/ionization mass spectrometry of polysaccharides with 2',4',6'-trihydroxyacetophenone as matrix. Rapid Commun Mass Spectrom., 21, 2137-46.

Chang, C. C., Liang, Y. C., Klutz, A., Hsu, C. I., Lin, C. F., Mold, D. E., Chou, T. C., Lee, Y. C. and Huang R. C. (2006) Reversal of multidrug resistance by two nordihydroguaiaretic acid derivatives, M4N and maltose-M3N, and their use in combination with doxorubicin or paclitaxel. Cancer Chemother Pharmacol., 58, 640-53.

C. Chan, H. Lam, Y.C. Lee, X.-M. Zhang (2006) Analytical method validation and instrument performance verification. Anal Bioanal Chem., 384(1), 22-3. No abstract available.

Jeong JC, Yoon CH, Lee WH, Park KK, Chang YC, Choi YH, Kim CH. (2005) Effects of Bambusae concretio Salicea (Chunchukhwang) on amyloid beta-induced cell toxicity and antioxidative enzymes in cultured rat neuronal astrocytes. J Ethnopharmacol., 98(3), 259-66.

Suzuki, N., Laskowski, M., Jr., and Lee, Y. C. (2004) Phylogenetic expression of Gal{alpha}1-4Gal on avian glycoproteins: Glycan differentiation inscribed in the early history of modern birds. Proc. Natl. Acad. Sci. U S A.

Locke, D., Bevans, C. G., Wang, L. X., Zhang, Y., Harris, A. L., and Lee, Y. C.(2004) Neutral, acidic, and basic derivatives of anthranilamide that confer different formal charge to reducing oligosaccharides. Carbohydr. Res., 339, 221-31.

Viswanathan, K., Lawrence, S., Hinderlich, S., Yarema, K.J., Lee, Y.C., and Betenbaugh, M.J. (2003) Engineering sialic acid synthetic ability into insect cells: identifying metabolic bottlenecks and devising strategies to overcome them. Biochemistry, 42, 15215-25.

Tomiya, N., Howe, D., Aumiller, J.J., Pathak, M., Park, J., Palter, K.B., Jarvis, D.L., Betenbaugh, M.J., and Lee, Y.C. (2003) Complex-type biantennary N-glycans of recombinant human transferrin from Trichoplusia in insect cells expressing mammalian [beta]-1,4-galactosyltransferase and [beta]-1,2-N-acetylglucosaminyltransferase II. Glycobiology, 13, 23-34.

Lee, R.T., and Lee, Y.C. (2003) Carbohydrate-binding properties of human neo-CRP and its relationship to phosphorylcholine-binding site. Glycobiology, 13, 11-21.

Choi, O., Tomiya, N., Kim, J.H., Slavicek, J.M., Betenbaugh, M.J., and Lee, Y.C. (2003). N-Glycan structures of human transferrin produced by Lymantria dispar (Gypsy moth) cells using the LdMNPV expression system. Glycobiology, 13, 539-48.

Abdul-Rahman, B., Ailor, E., Jarvis, D., Betenbaugh, M., and Lee, Y.C. (2002) Beta-(1-->4)-Galactosyltransferase activity in native and engineered insect cells measured with time-resolved europium fluorescence. Carbohydr. Res., 337, 2181-2186.

Fan, H.N., Liu, M.Z., and Lee, Y.C. (2002) Large-scale preparation of a-D-(1-4)-oligogalacturonic acids from pectic acid. Can. J. Chem., 80, 900-903.

Lee, R.T., Takagahara, I., and Lee, Y.C. (2002) Mapping the binding areas of human C-reactive protein for phosphorycholine and polycationic compounds. Relationship between the two types of binding sites. J. Biol. Chem., 277, 225-232.

Lee, S.J., Evers, S., Roeder, D., Parlow, A.F., Risteli, J., Risteili, L., Lee, Y.C., Feizi, T., Langen, H., and Nussenzweig, M.C. (2002) Mannose Receptor-Mediated Regulation of Serum Glycoprotein Homeostatis. Science, 295, 1898-1901.

Nagahori, N., Lee, R.T., Nishimura, S., Page, D., Roy, R. and Lee, Y.C. (2002) Inhibition of Adhesion of Type 1 Fimbriated Escherichia coli to Highly Mannosylated Ligands. Chemobiochem., 3, 836-844.

Lee, Y.C. (2001) Application of time-resolved fluorometry of lanthanide in glycobiology. Anal. Biochem., 297, 123-127.

Suzuki, N., Khoo, K. H., Chen, H.-C., Johnson, J. R. and Lee, Y.C. (2001) Isolation and characterization of major glycoproteins of pigeon egg white. Ubiquitous presence of unique N-glycans containing Gala1--4Gal. J. Biol. Chem., 276, 23221-23229.

Takahashi, N., Khoo, K. H., Suzuki, N., Johnson, J. R. and Lee, Y.C. (2001). N-Glycan structures from the major glycoprotein of pigeon egg white. J. Biol. Chem., 276, 23230-23239.

Tomiya, N., Ailor, E., Lawrence S.M., Betenbaugh, M.J. and Lee, Y.C. (2001) Determination of nucleotides and sugar nucleotides involved in protein glycosylation by high performance amino-exchange chromatography: Sugar nucleotide contents in cultured insect cells and mammalian cells. Anal. Biochem., 293, 129-137.

Keyhani, N.O., Wang, L.-X., Lee, Y.C. and Roseman, S. (2000) The chitin disaccharide, N-N'-diacetylchitobiose, is catabolized by Escherichia coli and is transported/phosphorylated by the phosphoenolpyruvate: Glucose phosphotransferase system. J. Biol. Chem., 275, 33084-33090.

Yasuo Oda, Katsuyoshi Nakayama, Badarulhisam Abdul-Rahman, Mitshihiro Kinoshita, Osamu Hashimoto, Nana Kawasaki, Takao Hayakawa, Kazuaki Kakehi, Noboru Tomiya, and Yuan C. Lee. (2000) Crocus sativus Lectin Recognizes (Man)3-GlcNAc in the N-Glycan Core Structure. J. Biol. Chem., 275, 26772-26779.

Lauc, G., Lee, R., Dumic, J., and Lee, Y. C. (2000) Photoaffinity glycoprobes -- a new tool for the identification of lectins. Glycobiology, 10, 357.

Lawrence, S.M., Huddleston, K.A., Pitts, L.R., Nguyen, N., Lee, Y.C., Vann, W.F., Coleman, T.A., and Betenbaugh, M.J. (2000) Cloning and expression of the human N-acetylneutrminic acid phosphate synthase gene with 2-keto3-deoxy-D-glycero-D-galacto-nononic acid biosynthetic ability. J. Biol. Chem., 275, 17869.

Lee, Y.C. and Lee, R.T. (2000) Affinity enhancement by multivalent lectin-carbohydrate interaction. Glycoconjugate J., 17, 543-551.

Oda., Y., Nakayama, K., Abdul-Rahman, B., Kinoshita, M., Hashimoto, O., Kawasaki, N., Hayakawa, T., Kakehi, K., Tomiya, N. and Lee, Y.C. (2000) Crocus sativus Lectin recognizes Man3GlcNAc in the N-glycan core structure. J. Biol. Chem., 285, 26772-26779.

Research Associate

Reiko T. Lee

Postdoctoral Fellow

Yeong-Jiunn Jang

Visiting Postdoctoral Fellow

Cheng-Tai Chen

Visiting Students

Sylvain Liao
Shu-Chuan Lin

Undergraduate Students

Cindy Tsai
Olga Guzovsky
Kelly Chuang