Xuefei Huang

Organic Chemistry, Synthetic Chemistry, Nanoscience and Immunology


Professor

426 CEM

517-353-1076


Associate Chair for Research


Research webpage


Primary Research Area

Organic (Or)

Other Area(s) of Interest

Analytical (An)

Biological (Bi)

Material (Ma)

Research

(Research Description PDF)

The chemistry of carbohydrates and their biology is the major emphasis of our research. Carbohydrates play important roles in many biological processes such as inflammation, tumor metastasis, bacterial and viral infections. Detailed understanding of many of these processes is still lacking. Building on our strength in synthetic chemistry, we take a multi-disciplinary approach to study this important class of molecules. Our research encompasses several areas including synthetic organic chemistry, nanoscience and chemical immunology.

In the synthetic chemistry area, we are developing novel methodologies for assembling biologically active oligosaccharides and glycoconjugates. Traditional carbohydrate synthesis is very tedious and time-consuming. In order to expedite the synthetic process, we have developed novel one-pot glycosylation methodologies, where multiple sequential glycosylation reactions are carried out in a single reaction flask to yield desired oligosaccharides without time-consuming intermediate purifications. One of the methods we developed, the pre-activation based iterative one-pot method, has achieved higher synthetic efficiencies in several syntheses compared to the automated solid phase based method. We are applying the methods we developed to total synthesis of a wide range of highly complex oligosaccharides and glycoconjugates. A representative example of the molecules we have synthesized is shown in Fig 1. We are continuing to synthesize biologically important carbohydrates.

Fig 1.

 

In our nanoscience program, we combine the multifaceted properties of carbohydrates with the unique functions of nanoparticles by immobilizing carbohydrates onto the external surface of magnetic nanoparticles. The magnetic glyco-nanoparticles (MGNPs) produced retain the biological recognition of carbohydrates and at the same time enhance the avidity of carbohydrate-receptor interactions by thousands of times. The magnetic nature of the nanoparticles enables us to use magnetic resonance imaging (MRI) as a non-invasive method for disease detection. An example of this is shown in Fig. 2, where the presence of atherosclerotic plaques (the major cause of heart attack and stroke) in rabbits can be easily detected by MRI after injection of the MGNPs. Besides detection and imaging applications, we are exploring the utility of MGNPs for targeted drug delivery. We found that by incorporating drugs onto MGNPs, the cytotoxicity of the drugs towards cancer cells can be significantly enhanced. We are continuing to develop magnetic glyco-nanoparticles for non-invasive detection and treatment of diseases such as cancer, atherosclerosis and Alzheimer’s disease.

Fig 2.

 

In the immunology area, harnessing the awesome power of body’s immune system to fight cancer is an attractive strategy to cancer treatment. It is well known that many tumor cells have unique carbohydrate structures over-expressed on the cell surface. However, the low immunogenecities of these tumor associated carbohydrate antigens present a formidable challenge for the development of carbohydrate based anti-cancer vaccines. To overcome this obstacle, we are developing novel carrier systems such as cowpea mosaic virus capsid (CPMV) and bacteriophage Qβ to deliver tumor associated carbohydrate antigens to the immune system and to boost the immune responses against carbohydrates as diagrammed in Fig. 3. We discovered that antigens displayed in a highly organized manner can elicit much stronger immune responses. Vaccination with our constructs successfully protected the immunized mice from tumor development in several tumor models. This is an excitingly new direction for the development of anti-cancer vaccines.

Fig 3.

 

Selected Publications

Chemical Synthesis of Syndecan-3 Glycopeptides Bearing Two Heparan Sulfate Glycan Chains, Yoshida, K.; Yang, B.; Yang, W.; Zhang, Z.; Zhang, J.; Huang, X., Angew. Chem. Int. Ed. 2014, 53, 9051-9058.

Design and Syntheses of Hyaluronan Oligosaccharide Conjugates as Inhibitors of CD44-Hyaluronan Binding, Lu, X.; Huang, X., Glycoconjugate J. 2015, 32, 549-556; (special issue dedicated to Chemical Glycobiology).

Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-based Anti-cancer Vaccine, Yin, Z.; Wright, W. S.; McKay, C.; Baniel, C.; Kaczanowska, K.; Bentley, P.; Gildersleeve, J. C.; Finn, M. G.; BenMohamed, L.; Huang, X., ACS Chem. Biol. 2015, 10, 2364-2372.

Lipopeptide Coated Iron Oxide Nanoparticles as Potential Glyco-Conjugate Based Synthetic Anti-Cancer Vaccines, Sungsuwan, S.; Yin, Z.; Huang, X., ACS Appl. Mater. Interface 2015, 7, 17535−17544.

Divergent Synthesis of Heparan Sulfate Oligosaccharides, Dulaney, S. B.; Xu, Y.; Wang, P.; Tiruchinapally, G.; Wang, Z.; Kathawa, J.; El-Dakdouki, M. H.; Yang, B.; Liu, J.; Huang, X., J. Org. Chem. 2015, 80, 12265-12279.

Chemical Synthesis of GM2 Glycans, Bioconjugation with Bacteriophage Qβ and the Induction of Anti-Cancer Antibodies, Yin, Z.; Dulaney, S.: McKay, C. S.; Baniel, C.; Kaczanowska, K.; Ramadan, S.; Finn, M. G.; Huang, X., ChemBiochem 2016, 17, 174-180.

Steric Trapping Reveals a Cooperativity Network in the Intramembrane Protease GlpG under Native Condition, Guo, R.; Gaffney, K.; Yang, Z.; Kim, M.; Sungsuwan, S.; Huang, X.; Hubbell, W.; Hong, H., Nat. Chem. Biol. 2016, 12, 353–360.

CV

B.S., 1994, Univ. of Science and Technology of China

M.A. 1995, M.Phil. 1998, Columbia Univ.

Ph.D., 1999, Columbia Univ.

Assistant Professor, 2002-2006 Univ. of Toledo

Associate Professor, 2006-2008 Univ. of Toledo

Awards/Honors

2016 Mellville L. Wolfrom Award American Chemical Society
2013 American Chemical Society Fellow
2011 ACS Carbohydrate division Horace S. Isbell award
2009 New Investigator Award from the ACS Carbohydrate Division
2008 Distinguished Faculty Award Chinese-American Chemistry Professor Association
2007 Dion D. Raftopoulos Outstanding Research Award Sigma Xi
2006 NSF CAREER Award
1994 - 1999 Faculty Fellowship Columbia Unversity
1993 Yi Lida Award for Outstanding Laboratory Works USTC
1992 Zhang Zhongzhi Award for Outstanding Undergraduates, 1992 USTC