Cancer cells undergo dramatic changes in carbohydrate expression during the onset and progression of disease. As a result, there has been considerable interest in understanding why these changes occur, how they contribute to the disease, and exploiting these changes for clinical use. Carbohydrate binding antibodies and lectins play a critical role in this research for several reasons. First, antibodies and lectins are used extensively to detect and monitor changes in carbohydrate expression. In this capacity, they are used for basic research, as diagnostics, and as therapeutic agents. A comprehensive understanding of their specificity is critical for proper use and interpretation of results. Until recently, this information was not readily available. With the advent of carbohydrate microarray technology, or glycan arrays, we can now rapidly analyze binding of these proteins to a wide variety of carbohydrate antigens. In the past, we have screened a large set of commercially available lectin and antibody reagents used in the research community. We found that many of these reagents did not display the expected specificity. The information we provided regarding specificity will enable better use of these reagents and facilitate interpretation of results. Recently, we have been profiling selected antibodies and lectins in collaborations with researchers at the German Cancer Research Institute, Abeome Corp., and University of Washington-St. Louis. In each case, the antibodies and lectins selectively bind tumors and display anti-cancer activity. They appeared to bind glycans, but the identities of the carbohydrate ligand(s) were unknown. The array has been used to profile the binding properties of these proteins and identify their ligands. In addition, the array can be used to develop new antibodies and lectins for monitoring new carbohydrate antigens. The array has been instrumental in the development of monoclonal antibodies that bind the GalNAca1-3Gal antigen. Using these antibodies, we have found that this carbohydrate antigen has altered expression on squamous cell carcinomas of the cervix and that changes in expression correlate with prognosis.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Cancer Institute Division of Basic Sciences
Zip Code
Kumar, Pardeep; Kuhlmann, F Matthew; Chakraborty, Subhra et al. (2018) Enterotoxigenic Escherichia coli-blood group A interactions intensify diarrheal severity. J Clin Invest 128:3298-3311
Lubkowski, Jacek; Durbin, Sarah V; Silva, Mariana C C et al. (2017) Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth. FEBS J 284:429-450
Gibadullin, Ruslan; Farnsworth, David Wayne; Barchi Jr, Joseph J et al. (2017) GalNAc-Tyrosine Is a Ligand of Plant Lectins, Antibodies, and Human and Murine Macrophage Galactose-Type Lectins. ACS Chem Biol 12:2172-2182
Sterner, Eric; Peach, Megan L; Nicklaus, Marc C et al. (2017) Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies. Cell Rep 20:1681-1691
Sterner, Eric; Flanagan, Natalie; Gildersleeve, Jeffrey C (2016) Perspectives on Anti-Glycan Antibodies Gleaned from Development of a Community Resource Database. ACS Chem Biol 11:1773-83
Gildersleeve, Jeffrey C; Wright, Whitney Shea (2016) Diverse molecular recognition properties of blood group A binding monoclonal antibodies. Glycobiology 26:443-8
Rho, Jung-hyun; Mead, Judson R; Wright, W Shea et al. (2014) Discovery of sialyl Lewis A and Lewis X modified protein cancer biomarkers using high density antibody arrays. J Proteomics 96:291-9
Wang, Linlin; Cummings, Richard D; Smith, David F et al. (2014) Cross-platform comparison of glycan microarray formats. Glycobiology 24:507-17
Hong, Xia; Ma, Mark Z; Gildersleeve, Jeffrey C et al. (2013) Sugar-binding proteins from fish: selection of high affinity ""lambodies"" that recognize biomedically relevant glycans. ACS Chem Biol 8:152-60
Luo, Ming; Velikovsky, C Alejandro; Yang, Xinbo et al. (2013) Recognition of the Thomsen-Friedenreich pancarcinoma carbohydrate antigen by a lamprey variable lymphocyte receptor. J Biol Chem 288:23597-606

Showing the most recent 10 out of 24 publications