Education and Training

B.S. Beijing University, 1991
Premedical Studies

M.D. Peking Union Medical College, 1996

Ph.D. Department of Biochemistry and Molecular Genetics, Cornell University, Mentor: Dr. Linda K. Nicholson, 2000

Postdoctoral Training, Department of Biochemistry and Molecular Biophysics, Columbia University, Mentor: Dr. Arthur G. Palmer, 2001-2004

Contact

E-mail: wangc5@rpi.edu
Tel: (518) 276-3497
Fax: (518) 276-2344

Office: Biotech Center Rm. 2229

Rensselaer Polytechnic Institute
110 8th Street
Troy, NY 12180

Research Interests

Alzheimer’s disease, Aβ, protein aggregation, mechanism and applications of protein splicing, protein recognition, protein dynamics, membrane proteins, NMR spectroscopy.

My research focuses on protein structure and dynamics in Alzheimer’s disease and protein splicing.

Alzheimer’s Disease

Alzheimer’s disease is the most common type of dementia and is a serious threat to the health of the aging population all over the world. Amyloid β-peptide (Aβ) plays a key role in causing Alzheimer’s disease. We are studying various aspects of Aβ structure, dynamics, interaction and aggregation:

• The aggregation of Aβ is a critical step in the pathogenesis of Alzheimer’s. We study the aggregation of Aβ using a multi-disciplinary approach. We employ techniques such as nuclear magnetic resonance (NMR), atomic force microscopy, CD, fluorescence, mutagenesis and theoretical modeling.
• The interaction of Aβ with cellular targets is likely the mechanism of Aβ toxicity, which disrupts neural networks and eventually leads to memory failure. We are pursuing the structural studies of Aβ interactions with proteins such as ABAD (Aβ-binding Alcohol Dehydrogenase) and RAGE (Receptors for Advanced Glycation Product). The high-resolution structural information obtained will be the basis of rational drug design to prevent such abnormal interactions.
• Protective mechanisms in Alzheimer’s disease. Enhancing the protective mechanism in Alzheimer’s is an overlooked pathway to prevent and treat Alzheimer’s. Recently, we propose a critical, protective function for Aβ40 in Alzheimer’s. Currently we are exploring the mechanism of such a protective effect and the possible application of Aβ40 to the management of Alzheimer’s.
• Static protein structures alone often cannot explain the mechanisms of protein function, because protein function, such as folding, recognition, catalysis, energy generation and transduction, and transport, invariably involves protein motion. Solution NMR is the most powerful technique for studying protein dynamics. We are studying the dynamics of Aβ and its role in Aβ aggregation and interaction.

Protein Splicing

Protein splicing is a precise post-translational process in which an intervening protein sequence, intein, is removed from a precursor protein with the concomitant ligation of the flanking sequences, N- and C-exteins. Although the basic steps of protein splicing are well-known, the catalytic mechanisms of intein splicing are still poorly understood. Advancing our fundamental knowledge of protein splicing can have two major impacts: 1. Inteins have found extensive applications in protein engineering and biotechnology and therefore are an indispensable tool for biomedical research and potentially for therapies of diseases. 2. Because only unicellular organisms have inteins vital for their survival, intein inhibitors can develop into a new class of antimicrobial drug with little toxicity for human cells, especially for Mycobacterium tuberculosis (Mtu). Projects involving protein splicing are as follows:

• Testing novel mechanistic hypotheses in protein splicing. We proposed two new mechanistic hypotheses for conserved residues H73 and D422 in Mtu RecA intein. These two hypotheses have been supported by diverse experimental evidence from genetics, in vivo splicing data in intein mutants, solution NMR studies and by theoretical calculations. We are testing these two hypotheses using a combination of NMR structural biology methods, biochemical characterization of splicing reaction and molecular dynamics simulation. The long term goal is to delineate the complete catalytic mechanisms of protein splicing by applying solution NMR in an interdisciplinary approach for studying enzyme catalysis, structure, dynamics and function.
• We are also exploring the application of protein splicing to the treatment of diseases and biosensing, using directed evolution and structural modeling.

Selected Publications

Wang, C., Xi, J., Begley, T. P., Nicholson, L.K. (2001), “Solution Structure of ThiS and Implications for the Evolutionary Roots of Ubiquitin”, Nature Structural Biology 8, 47-51. Selected as Editor’s Choice in Jan 19, 2001 issue of Science.

Wang, C., Pawley, N., Nicholson, L. (2001). “The Role of Backbone Motions in Ligand Binding to the c-Src SH3 Domain”, Journal of Molecular Biology, 313, 873-887.

Wang, C., Rance, M., Palmer, A.G. (2003). “Mapping Chemical Exchange in Proteins with MW > 50 kD”, Journal of the American Chemical Society, 125: 8968-8969. Selected as a “Must Read” by faculty of 1000 website (www.facultyof1000.com).

Wang, C., Karpowich, N.K., Hunt, J.F., Rance, M., Palmer, A.G. (2004) “Dynamics of ATP-Binding Cassette Contributes to Nucleotide Binding and Energy Transduction”, Journal of Molecular Biology 342:525-537.

Palmer, A.G., Grey, M.J., Wang, C. (2005). “Solution NMR Spin Relaxation Methods for Characterizing Chemical Exchange in High Molecular Weight Systems”, Methods in Enzymology 394: 430-465.

Yan, Y. and Wang, C. (2006) “Aβ42 is More Rigid than Aβ40 in the C-Terminus: Implications for Aβ Aggregation and Toxicity”, Journal of Molecular Biology 364: 853-862.

Yan, Y., Liu, Y., Sorci, M., Belfort, G., Lustbader J.W., Yan, S.D. and Wang, C. (2007) “Surface Plasmon Resonance and Nuclear Magnetic Resonance Studies of ABAD-Aβ Interaction” Biochemistry 46: 1724-1731.

Sgourakis, N., Yan, Y., McCallum, S., Wang, C. and Garcia, A.E. (2007) “The Alzheimer's peptides Aβ40 and 42 adopt distinct conformations in water: A combined MD / NMR study” Journal of Molecular Biology 368:1448-1457.

Yan, Y. and Wang, C. (2007) “Aβ40 protects non-toxic Aβ42 monomers from aggregation” Journal of Molecular Biology 369:909-916.

Yan, Y., Liu, J., McCallum, S.A., Yang, D. and Wang, C. (2007) “Methyl dynamics of the amyloid-β peptides Aβ40 and Aβ42.” Biochem Biophys Res Commun. 362:410-4.

Yan, Y., McCallum, S.A., Wang, C. (2008). M35 oxidation Causes Aβ40-like Changes in Structure and Dynamics in Aβ42. Journal of the American Chemical Society. Published online April 1, 2008.