Denong Wang, M.D., Ph.D.

Senior Research Associate

Research:

We are focusing on post-genomic research and technologies. Our strategies are

a) to take the advantage of our immunological expertise to develop specific tools for functional analysis of genes and their pathways at the protein or post-translational levels;

b) to establish biochip-based high throughput technologies to enable post-genomic research at multiple molecular levels, including nucleic acid, protein and carbohydrate;

c) to focus on specific model systems for our post-genomic investigations;

d) to seek for collaboration with emphasis on but not limited to the fields of immunology and infectious disease to extend further our efforts.

Antigen/antibody microarrays. Our current efforts are focusing on the development of a carbohydrate-based microarray system to extend the scope of biomedical research on carbohydrate-mediated molecular recognition and anti-infection responses. This system will be extended to develop antibody-based biochips to enable differential analysis of protein expression, glycosylation and other post-translational modifications in a global scale.

cDNA microarrays. We are focusing on the development of a highly sensitive and relative inexpensive method to enable clinical application of cDNA microarrays. A team of collaborators, including other CGC laboratories and industry researchers, are currently working on different aspects of the technology. These include design and production of customized cDNA microarrays, investigation of methods for unbiased amplification of expression signals and development of a pattern-recognition based algorithm for microarray data processing.

Hybridoma and antibody libraries. Both hybridoma methodology and phage-antibody library systems have been routinely applied in our laboratory for production of mouse monoclonal antibodies and of engineered single chain antibodies. Specific targets include proteins of disease-related genes and of newly discovered genes whose function is currently unknown.

Model systems for post-genomic research.

a) Diversities of HIV-1 and host defenses;

b)T-independent pathway of IgA responses;

c) Molecular regulation of synapse formation (Aplysia).

Other ongoing research projects.

A) Monoclonal antibodies for lymphoma-associated proteins;

b) Human lymphoma and myeloma protein with anti-carbohydrate activities;

c) Antibodies recognizing conformational epitopes of membrane-bound proteins;

d) Celiac disease (Human).

Publications:

Wang, D., Hubbard, J. M. and Kabat, E. A. Modeling Study of the Antibody Combining Sites to (a1-6)dextrans: Predictions of the Conformational Contribution of VL-CDR3 and Jk Segments to Groove-type Combining Sites (1993) J. Bio. Chem., 168, 20584-20589.

Wang, D., Wells, S. M., Stall, A. M. and Kabat, E. A. Reaction of germinal centers in the T-cell-independent response to the bacterial polysaccharide a(1®6)dextran. (1994) Proc. Natl. Acad. Sci. U.S.A. 91:2502-2506.

Wang D and Kabat E.A., Carbohydrate Antigens (Polysaccharides), Chapter 9, In: Structure of Antigens, Volume Three, (ed. M.H.V.Van Regenmortal), pp.247-276, CRC Press, Boca Raton New York London Tokyo, 1996.

Wang D. and Kabat E.A. Antibodies, Specificity In: Encyclopedia of Immunology, Second Edition, (ed. Delves and Roitt), pp.148-154, Academic Press, London, 1998.

Schacher, S., Wu, F., Panyko, J. D., Sun, Z-Y and Wang, D. Expression and branch-specific accumulation of mRNA are regulated by synapse formation and interaction with specific postsynaptic targets. (1999), J. Neurosci., 19, 6338-47.

Wang, D., Erlanger, B.F. and Kabat, E. A. Methods relating to immunogenic dextran-protein conjugates (2001), Patent No. US 6,287,568 B1, Sep.11, 2001.

Wang, D. T-independent IgA responses to microbial polysaccharides.(2001) In: Molecular Immunology of Complex Carbohydrates 2, (ed. A.M. Wu), Kluwer Academic/Plenum Publisher, New York Boston Dordrecht London Moscow.

Wang, D., Carbohydrate microarrays and their application potential. (2001). Invited Lecture in Workshop on Protein Microarray Technologies, April 10, 2001, San Francisco, CA, USA

Wang, D., Trummer, B. J., Liu, S., Wang, A., and Zhou, H. (2001). A carbohydrate-based microarray system for characterizing AIDS-associated microbial infections. Abstract & Poster for The AIDS Vaccine 2001 Conference, September 5-8, 2001, Philadelphia, PA, USA

Wang, D, Shaoyi L., Trummer, B. J., and Wang, A. Carbohydrate microarrays leading to