Yuan Chuan Lee Professor Department of Biology Secondary Appointment, Department of Chemistry CMDB Graduate Program Faculty B.S. National University of Taiwan Ph.D. University of Iowa Postdoctoral University of California

[Research Interests] [Representative Publications] [Lab Members]

RESEARCH INTERESTS

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. 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.

REPRESENTATIVE PUBLICATIONS

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.   Application of time-resolved fluorometry of lanthanide in glycobiology.(2001).  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.

• 1992 FASEB 6.13
• 1995 Accounts of Chemical Research 28.8
• 2000 J. Biol. Chem. 275
• Analyst 128, 440-6

Dr. Lee was recipient of the Clude Hudson Award from American Chemical Society in 2001.

Lab Members

Research Associates:
Reiko T. Lee
Tomiya Noboru

Postdoctoral Fellow :
Yeong-Jiunn Jang

  Visiting  Student:
Sylvain Liao

Undergraduate Student :
Hanna Yoo