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. 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.

REPRESENTATIVE PUBLICATIONS

Gillmeister, M.P., Tomiya, N., Jacobia, S.J., Lee, Y.C., Gorfien, S.F., 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. Glycoconj J.[Epub ahead of print]

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

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

Suzuki, N., Su, T.H., Wu, S.W., Yamamoto, K., Khoo, K.H., 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., Tsai, P.J., Lee, Y.C., Chen, Y.C. 2008. Affinity capture of uropathogenic Escherichia coli using pigeon ovalbumin-bound Fe3O4@Al2O3 magnetic nanoparticles. Anal Chem. 80:5425-32.

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.

Former Associates of the Y.C. Lee laboratory elected to the Hopkins Society of Scholars

2009 Lai-xi Wang, Baltimore
Dr. Lai-Xi Wang is an associate professor in the Department of Biochemistry and Molecular Biology in the Institute of Virology at the University of Maryland School of Medicine. His research has provided important new insights for HIV vaccine design and propelled him to the forefront of the anti-HIV field. Specifically, he has explored carbohydrate antigens as a target for an HIV vaccine by synthesizing novel oligosaccharides (saccharide polymers) to mimic the antigens on the viral envelope. Dr. Wang has also developed a highly efficient method for making glycoproteins that carry defined oligosaccharides, which opens a new avenue for rapid access to various glycoproteins that are essential for probing the structure and function of this class of important biological molecules. In recognition of his achievements, Dr. Wang received the 2004 Young Investigator Award in Carbohydrate Chemistry from the American Chemistry Society. Dr. Wang was a postdoctoral fellow in the Department of Biology from 1993 to 1997.

2007 Yoshi Ichikawa, San Diego
Yoshi Ichikawa is senior director of the Chemistry at Optimer Pharmaceuticals, where he oversees the application of innovative sugar-based medicinal chemistry to improve the properties of drugs. He took on that role after two stints at Johns Hopkins, in 1987 as a postdoctoral fellow under Yuan C. Lee in the Krieger School's Department of Biology and later as an associate professor in the Department of Pharmacology and Molecular Sciences at the School of Medicine. There he created new and extremely powerful inhibitors of glycohydrases, including those required for sugar metabolism and DNA repair and synthesis. The practical application of this discovery can be found in effective therapeutics for bacterial and parasite infections. He was nominated by Yuan C. Lee, professor, Biology Department, Krieger School of Arts and Sciences.

2003 Kevin G. Rice, Iowa City, Iowa
As a National Institutes of Health postdoctoral fellow, Dr. Rice spent three years at Johns Hopkins studying the relationships between carbohydrates and carbohydrate-binding proteins. His work has become a highly respected classic in the field. Now a professor and division head of medicinal and natural products chemistry at the College of Pharmacy at the University of Iowa (his alma mater), Dr. Rice has trained many Ph.D.'s and postdoctoral fellows. In 2001, he earned the American Chemical Society's Horace S. Isbell Award, a coveted award bestowed only to scientists under 40 years old, for his development and application of targeted gene delivery systems, based on carbohydrate-recognition in biological systems.

2000 Hiroshi Tomoda, director of the Institute for Biological Function, the Kitasato Institute, Tokyo
At Hopkins: Postdoctoral fellow, Department of Biology and the Kennedy Institute, 1987-89. Nominated by Yuan C. Lee. Hiroshi Tomoda's lifelong passion for isolating biomedically useful microbial products has led him to discover compounds that promise to open new horizons in solving problems of arteriosclerosis and even HIV infection, as well as compounds that are effective in lowering cholesterol levels. Holder of more than 20 patents on compounds, Tomoda not only has produced practical products but provided insights into understanding enzyme mechanisms.

1995 Noriko Takahashi, Handa-City, Japan
Dr. Takahashi has made two important contributions in the field of glycobiology, both of which help scientists analyze the structure of carbohydrates in glycoconjugates. She discovered glycoamidase, an enzyme which has become an indispensable tool for studying glycoproteins, and she developed new chromatic methods for carbohydrate analysis. Dr. Takahashi is also distinguished in the history of Japan: she was the first woman graduate of Nagoya University (1951) and the first woman in Japan to obtain an engineering degree.

1995 Shin-Ichiro Nishimura, Sapporo, Japan
Dr. Nishimura's work in polymer chemistry and glyco- biology holds promise for new treatments of diseases such as influenza and AIDS; the work has produced a flurry of publications-more than 100 in nine years-and remarkable professional recognition. Since taking his Ph.D. in 1987, he has risen to become professor and director of the Division of Biological Science in the graduate school at Hokkaido University, as well as an editor of scientific journals and a member of the advisory boards of several scientific associations.

1985, Dr. Te Pao Wang, Shanghai, China
While at Johns Hopkins, Dr. Wang carried out pioneering studies in an area of biochemistry that became important in developing basic approaches to modern enzymology. His recent research, on the structure and function of transfer RNAs, culminated in the synthesis of several transfer RNAs and is recognized throughout the world as an important contribution to molecular biology and biochemistry.

Noriko Takahashi, Handa-City, Japan
Dr. Takahashi has made two important contributions in the field of glycobiology, both of which help scientists analyze the structure of carbohydrates in glycoconjugates. She discovered glycoamidase, an enzyme which has become an indispensable tool for studying glycoproteins, and she developed new chromatic methods for carbohydrate analysis. Dr. Takahashi is also distinguished in the history of Japan: she was the first woman graduate of Nagoya University (1951) and the first woman in Japan to obtain an engineering degree.

Lab Members

Research Associates:
Reiko T. Lee
Tomiya Noboru

Postdoctoral Fellow:
Yeong-Jiunn Jang

Visiting Postdoctoral Fellow:
Cheng-Tai Chen

  Visiting  Student:
Sylvain Liao
Shu-Chuan Lin

Undergraduate Student :
Cindy Tsai
Olga Guzovsky
Kelly Chuang