Research in the Moremen lab focuses on the structure, regulation, and localization of enzymes involved in the biosynthesis, recognition, and catabolism of mammalian glycoproteins. Carbohydrate structures on glycoproteins contribute to many biological recognition events during development, oncogenic transformation, and cell adhesion. In addition, protein-linked glycans can influence bioactivity, folding, localization, and immunogenicity of the attached polypeptide. Large numbers of intracellular and extracellular proteins contain covalently bound oligosaccharides, including enzymes, cell-surface receptors, hormones, immunoglobulins, and viral antigens. Alterations in the synthesis and degradation of these structures can also occur in human genetic diseases and cancer. Despite the ubiquity of glycoprotein structures, much is still unknown about the regulation of the glycosylation pathway and aspects of structure and function of the processing enzymes. Many questions also remain regarding oligosaccharide catabolism in different intracellular compartments as well as the specificity and regulation of protein-carbohydrate interactions during development.
Work in the Moremen lab is focused on four main areas: (1) characterization of mammalian glycoprotein biosynthesis and catabolism by the cloning, large-scale expression, biochemical characterization, and structure determination of the mammalian enzymes involved in these processes, (2) determination of the structural and molecular basis for the enzyme-substrate interactions for glycosidases and glycosyltransferases including mechanistic studies and identification of selective inhibitors, (3) developing technologies for detailed transcript profiling for glycan-related genes and correlating glycosylation enzyme expression with cellular glycan structures and (4) characterization of endoplasmic reticulum (ER) and Golgi enzymes involved in glycan biosynthesis and quality control degradation of misfolded nascent glycoproteins in the ER. Each of these research programs is supported by grant funding by the National Institutes of Health.