My laboratory utilizes carbohydrate chemistry to develop synthetic resources for further application in our investigations of glycoprotein biosynthesis. One area of study is the investigation of human galactosyl-, fucosyl-, and sialyltransferases implicated in the biosynthesis of cancer related glycoconjugates. Another program seeks to identify and characterize sulfotransferases present in different tumor cell lines and human tissue, in order to elucidate the biosynthetic pathway of sulfoglycoconjugates.
Information obtained for these programs leads us to develop studies into cell adhesion processes. Cell adhesion plays an important role in chronic inflammatory diseases. In addition, the cell adhesion process may be exploited by cancer cells to metastasize after entering the blood stream. Major effort is being centered on the prevention of initial adhesion events between circulating leukocytes and endothelium involving two families of cell surface receptors: the selectins and integrins. The family of selectins contains three members: E,P and L-selectin. All of our efforts are directed at understanding the glycobiology of cancer and related diseases. Phenotypic characterization of the unique cell surface markers of these stem-like cells may be better than use of cancer cell cultures under conventional methods. We hypothesize that the "glycan signature" of Prostate cancer cells stem cells (PCSCs) differentiates them from non-cancer prostate stem cells (Non-PCSCs), and the "glycan signature" evolves during the pathogenesis of prostate cancer and contributes causally to the disease phenotype.
Liu G, Marathe DD, Matta KL, Neelamegham S. Systems-level modeling of cellular glycosylation reaction networks: O-linked glycan formation on natural selectin ligands. Bioinformatics. 2008 Dec 1;24(23):2740-7.
Marathe DD, Chandrasekaran EV, Lau JT, Matta KL, Neelamegham S. Systems-level studies of glycosyltransferase gene expression and enzyme activity that are associated with the selectin binding function of human leukocytes. FASEB J. 2008 Dec;22(12):4154-67.
Chandrasekaran EV, Xue J, Xia J, Locke RD, Matta KL, Neelamegham S. Reversible sialylation: synthesis of cytidine 5'-monophospho-N-acetylneuraminic acid from cytidine 5'-monophosphate with alpha2,3-sialyl O-glycan-, glycolipid-, and macromolecule-based donors yields diverse sialylated products. Biochemistry. 2008 Jan 8;47(1):320-30.
Chandrasekaran EV, Xue J, Piskorz C, Locke RD, T�th K, Slocum HK, Matta KL. Potential tumor markers for human gastric cancer: an elevation of glycan:sulfotransferases and a concomitant loss of alpha1,2-fucosyltransferase activities. J Cancer Res Clin Oncol. 2007 Sep;133(9):599-611.
Beauharnois ME, Neelamegham S, Matta KL. Quantitative measurement of selectin-ligand interactions: assays to identify a sweet pill in a library of carbohydrates. Methods Mol Biol. 2006;347:343-58. Review.
Chandrasekaran EV, Xue J, Neelamegham S, Matta KL. The pattern of glycosyl- and sulfotransferase activities in cancer cell lines: a predictor of individual cancer-associated distinct carbohydrate structures for the structural identification of signature glycans. Carbohydr Res. 2006 Jun 12;341(8):983-94.
Xia J, Xue J, Locke RD, Chandrasekaran EV, Srikrishnan T, Matta KL. Synthesis of fluorinated mucin core 2 branched oligosaccharides with the potential of novel substrates and enzyme inhibitors for glycosyltransferases and sulfotransferases. J Org Chem. 2006 May 12;71(10):3696-706.
Ercan A, Panico M, Sutton-Smith M, Dell A, Morris HR, Matta KL, Gay DF, West CM. Molecular characterization of a novel UDP-galactose:fucoside alpha3-galactosyltransferase that modifies Skp1 in the cytoplasm of Dictyostelium. J Biol Chem. 2006 May 5;281(18):12713-21.
Chandrasekaran EV, Xue J, Xia J, Chawda R, Piskorz C, Locke RD, Neelamegham S, Matta KL. Analysis of the specificity of sialyltransferases toward mucin core 2, globo, and related structures. identification of the sialylation sequence and the effects of sulfate, fucose, methyl, and fluoro substituents of the carbohydrate chain in the biosynthesis of selectin and siglec ligands, and novel sialylation by cloned alpha2,3(O)sialyltransferase. Biochemistry. 2005 Nov 29;44(47):15619-35.
Beauharnois ME, Lindquist KC, Marathe D, Vanderslice P, Xia J, Matta KL, Neelamegham S. Affinity and kinetics of sialyl Lewis-X and core-2 based oligosaccharides binding to L- and P-selectin. Biochemistry. 2005 Jul 12;44(27):9507-19.
Xue J, Song L, Khaja SD, Locke RD, West CM, Laine RA, Matta KL. Determination of linkage position and anomeric configuration in Hex-Fuc disaccharides using electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2004;18(17):1947-55.
Ketcham C, Wang F, Fisher SZ, Ercan A, van der Wel H, Locke RD, Sirajud-Doulah K, Matta KL, West CM. Specificity of a soluble UDP-galactose: fucoside alpha1,3-galactosyltransferase that modifies the cytoplasmic glycoprotein Skp1 in Dictyostelium. J Biol Chem. 2004 Jul 9;279(28):29050-9.