个人简介
Education History
B.S. 1994 (Chemistry) University of Science and Technology of China (USTC)
M.A. 1996, M. Phil. 1998 Columbia University in the City of New York
Ph.D. 1999 (Chemistry) Columbia University in the City of New York
Professional Experience
1994 - 1999 Graduate Research Assistant, ColumbiaUniversity
1999 - 2001 Postdoctoral Fellow, The Scripps Research Institute
2001 - 2002 Postdoctoral Fellow, Department of Chemistry, ColumbiaUniversity
2002 – 2006 Assistant Professor, Department of Chemistry, University of Toledo
2006 – 2008 Associate Professor, Department of Chemistry, University of Toledo
2008 – 2012 Associate Professor, Department of Chemistry, Michigan State University
2012 –present Professor, Department of Chemistry, Michigan State University
2013 – present Associate Chair for Research, Dept. of Chemistry, Michigan State Univ.
研究领域
The major emphasis of our research is on chemistry and biology of carbohydrates. Carbohydrates play important roles in many biological processes such as inflammation, tumor metastasis, bacterial and viral infections. Building on our strength in synthetic chemistry, we take a multi-disciplinary approach to study the functions and applications of these fascinating molecules. Our research encompasses several areas including synthetic organic chemistry, nanoscience and chemical immunology. Students and postdocs in our group are exposed to a wide variety of state-of-the-art research topics including organic synthesis, physical organic chemistry, nanotechnology, materials science, immunology, cancer biology and molecular imaging.
Synthetic organic chemistry
In the synthetic 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. Several representative examples of the molecules we have synthesized are shown below. We are continuing to synthesize biologically important carbohydrates.
Glyco-nanoscience
Carbohydrates play roles in many biological recognition events, which render them attractive as molecular recognition elements in biological sensor design. 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 MGNPs enables us to use magnetic resonance imaging (MRI) as a non-invasive method for disease detection. An example of this is shown below, 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.
Chemical Immunology
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. We discovered that antigens displayed in a highly organized manner can elicit much stronger immune responses. Furthermore, the antibody generated can recognize antigens on the surfaces of cancer cells and lead to death of the cancer cells expressing the antigens. This is an excitingly new direction for the development of anti-cancer vaccines.
近期论文
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Wu. X.; McKay, C.; Pett, C.; Yu, J.; Schorlemer, M.; Ramadan, S.; Lang, S.; Westerlind, U.; Finn, M. G.; Huang, X.* “Synthesis and Immunological Evaluation of Disaccharide bearing MUC-1 Glycopeptide Conjugates with Virus-Like Particle to Reduce Tumor Metastasis” ACS. Chem. Biol. 2019, in press.
Pawar, N. J.; Wang, L.; Higo, T.; Bhattacharya, C.; Kancharla, P. K.; Zhang, F.; Baryal, K.; Huo, C.-X.; Liu, J.; Linhardt, R. J.; Huang, X.; Hsieh-Wilson, L.* “Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly” Angew. Chemie. Int. Ed. 2019, in press.
Nilsson, J.; Brinkmalm, G.; Ramadan, S.; Gilborne, L.; Noborn, F.; Blennow, K.; Wallin, A.; Svensson, J.; Abo-Riya, M. A.; Huang, X.*, Larson, G.* “Synthetic Standard Aided Quantification and Structural Characterization of Amyloid-beta Glycopeptides Enriched from Cerebrospinal Fluid of Alzheimer’s Disease Patients”, Sci. Rep. 2019, 9, 5522 https://doi.org/10.1038/s41598-019-41897-5.
Huo, C.-X.; Dhara, D., Baliban, S. M.; Nick, S. T.; Tan, Z.; Simon, R.; Misra, A. K.; Huang, X.* “Synthetic and Immunological Studies of Salmonella Enteritidis O-antigen Tetrasaccharide as Potential Anti-Salmonella Vaccines” Chem. Commun. 2019, 55, 4519-4522.
Ramadan, S.; Yang, W.; Huang, X.* “Synthesis of Chondroitin Sulfate Oligosaccharides and Chondroitin Sulfate Glycopeptides” in Synthetic Glycome, Royal Society of Chemistry; Editor: Peng George Wang; 2018, 172-206 (invited chapter).
Yin, Z.; Wu. X.; Kaczanowska, K.; Sungsuwan, S.; Comellas-Aragones, M.; Pett C., Yu J.; Baniel, C.; Westerlind, U.; Finn, M. G.; Huang, X.* “Antitumor Humoral and T Cell Responses by Mucin‑1 Conjugates of Bacteriophage Qβ in Wild-type Mice” ACS Chem. Biol. 2018, 13, 1668-1676.
Li, Y.;Xiao, Y.;lin, H.;Reichel, D.;Bae, Y.;Lee, E.;Jiang, Y.;Huang, X.;Yang, C.and Wang, Z.;"In vivo β-catenin attenuation by the integrin α5-targeting nano-delivery strategy suppresses triple negative breast cancer stemness and metastasis" Biomaterials, 2018, 188, 160-174
Wu, X.;Yin, Z.;McKay, C.; Pett, C.;Yu, J.;Schorlemer, M.;Gohl, T.; Sungsuwan, S.;Ramadan, S.;Baniel, C.;Allmon, A.; Das, R.;Westerlind, U.;Finn, M.G.and Huang, X.;* "Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice", J. Am. Chem. Soc.2018, DOI:10.1021/jacs.8b08473
Yang, W.; Ramadan, S.; Orwenyo, J.; Kakeshpour, T.; Diaz, T.; Eken, Y.; Sanda, M.; Jackson, J.;* Wilson, A.;* Huang, X.* “Chemoenzymatic Synthesis of Glycopeptides Bearing Rare N-Glycan Sequences with or without Bisecting GlcNAc” Chem. Sci. 2018, 9, 8194-8206
Wang, P.; Cascio, F.; Gao, J.; Kayed, R. and Huang, X.* "Binding and neurotoxicity mitigation of toxic tau oligomers by synthetic heparin like oligosaccharides", Chem.Comm.2018, 54, 10120-10123
Hossaini Nasr, S.; Kouyoumdjian, H.; Mallet, C.; Ramadan, S.; Zhu, D. A.; Shapiro, E. M.; Huang, X.* “In vivo Detection of β-amyloid by Sialic Acid Decorated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer’s Disease”, Small, 2018, 14, 1701828
Xu, S.; Hossaini Nasr, S.; Chen, D.; Zhang, X.; Sun, L.; Huang, X.;* Qian, C.* “MiRNA Extraction from Cell-free Biofluid using Protein Corona Formed around Carboxyl Magnetic Nanoparticles” ACS Biomate. Sci. Eng. 2018, 4, 654-662.
Hossaini Nasr, S.; Tonson, A.; El-dakdouki, M. H.; Agnew, D.; Zhu, D. A.; Wiseman, R.; Qian, C.;* Huang, X.* “Effects of Nanoprobe Morphology on Cellular Binding and Inflammatory Responses: Hyaluronan Conjugated Magnetic Nanoworms for Magnetic Resonance Imaging of Atherosclerotic Plaques”, ACS Appl. Mater. Interface 2018, 10, 11495-11507.
Yang, B.; Yang, W.; Ramadan, S.; Huang, X.* “Pre-activation Based Stereoselective Glycosylations” Eur. J. Org. Chem., 2018, 1075-1096.
Yang, W.; Yang, B.; Ramadan, S.; Huang, X.* “Pre-activation Based Chemoselective Glycosylations: A Powerful Strategy for Oligosaccharide Assembly” Beilstein J. Org. Chem., 2017, 13, 2094-2114. PMCID: PMC5647719.
Sungsuwan, S.; Wu, X.; Huang, X.* “Evaluation of Virus Like Particle Based Tumor-Associated Carbohydrate Immunogen in a Mouse Tumor Model” in Methods in Enzymology, Elsevier; Editor: Barbara Imperiali; 2017, 597, 359-376 (invited chapter).p PMCID: PMC5772760.
Ramadan, S.; Yang, W.; Zhang, Z.; Huang, X.* “Synthesis of Chondroitin Sulfate A Bearing Syndecan-1 Glycopeptide”, Org. Lett., 2017, 19, 4838-4841. PMCID: PMC5772981.
Ramadan, S.; Yang, W.; Huang, X.* “Synthesis towards Heparan Sulfate Glycopeptides and Proteoglycans” in Chemical Biology of Glycoproteins, Royal Society of Chemistry; Editor: Zhongping Tan, Lai-xi Wang; 2017, 209-232 (invited chapter). DOI:10.1039/9781782623823-00209
Kavunja, H.; Lang, S.; Sungsuwan, S.; Yin, Z.; Huang, X.* “Delivery of Foreign Cytotoxic T-lymphocyte Epitope to Tumor Tissues for Effective Antitumor Immunotherapy against Pre-established Solid Tumor” Cancer Immunol. Immunother. 2017, 66, 451-460.
Thapa, R.*; Gorski, J.; Bogedin, A.; Maywood, M.; Clement, C.; Hossaini-Nasr, S.; Hanna, D.; Huang, X.; Roth, B. J.; Madlambayan, G.; Wilson, G. D. “Hyaluronan-mediated ferric oxide nanoparticles causes apoptosis of CD44 expressing head and neck squamous cell carcinoma cells” Int. J. Cancer Ther. Oncol. 2016, 4, 424.
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