Oligosaccharides, which are short sugar polymers, carry important biological information. When attached to proteins (glycoproteins) they control receptor recognition, intracellular sorting, cellular homing, and folding in the endoplasmic reticulum. As modifications of lipids (glycolipids), oligosaccharides can form membrane anchors, organize membrane lipid patches, and mediate adhesion of pathogens to host cell surfaces. We are currently studying how these information-carrying oligosaccharides are involved in cellular stress responses, particularly in human genetic diseases called Congenital Disorders Of Glycosylation, in which oligosaccharide assembly is defective. Our work involves enzymology, molecular biology, cell culture, carbohydrate chemistry, and analytical HPLC.
RESEARCH INTERESTS
Synthesis and Human Disorders of Glycoconjugates
Glycoconjugates of the Mammalian Endoplasmic Reticulum
Endoplasmic Reticulum Stress Responses
RECENT PUBLICATIONS
Shang, J. and Lehrman, M.A., "Metformin-stimulated mannose transport in dermal fibroblasts" Journal of Biological Chemistry, Vol 279:9703-9712, March 2004
Shang, J. and Lehrman, M.A., "Activation of glycogen phosphorylase with 5-aminoimidazole-4-carboxamide riboside (AICAR)" Journal of Biological Chemistry, Vol. 279:12076-12080, March 2004
Shang, J., and Lehrman, M.A., "Inhibition Of Mammalian RNA Synthesis By The Cytoplasmic Ca2+ Buffer BAPTA. Analyses Of [3H]Uridine Incorporation And Stress-Dependent Transcription." Biochemistry, 43:9576-9582, 2004
Gao, N., Shang, J., and Lehrman, M. A., "Analysis Of Glycosylation In CDG-Ia Fibroblasts By Fluorophore-Assisted Carbohydrate Electrophoresis: Implications For Extracellular Glucose And Intracellular Mannose-6-Phosphate." The Journal Of Biological Chemistry, 280:17901-17909, 2005
Shang, J., Gao, N. Kaufman, R. J., Ron, D., Harding, H.P., and Lehrman, M.A., "Translational Balancing By The eIF2alpha Kinase PERK Couples ER Glycoprotein Synthesis To Lipid-linked Oligosaccharide Flux." The Journal Of Cell Biology, 176:605-616, 2007
SIGNIFICANT PUBLICATIONS
Ware, F.E., Vassilakos, A., Jackson, M., Lehrman, M.A. and Williams, D.B., "The Molecular Chaperone Calnexin Binds Glc1Man9GlcNAc2 Oligosaccharide As An Initial Step In Recognizing Unfolded Glycoproteins." Journal of Biological Chemisty, 270:4697-4704, 1995
Ware, F.E. and Lehrman, M. A., "Expression Cloning Of A Novel Suppressor Of The Lec15 and Lec35 Glycosylation Mutations Of Chinese Hamster Ovary Cells." Journal of Biological Chemisty, 271:13935-13938, 1996
Doerrler, W. T. and Lehrman, M. A., "Regulation Of The Dolichol Pathway In Human Fibroblasts By The Endoplasmic Reticulum Unfolded Protein Response." Proc. Natl. Acad Sci. USA, 96:13050-13055 (Track II), 1999
Gao, N., Shang, J., and Lehrman, M. A., "Analysis Of Glycosylation In CDG-Ia Fibroblasts By Fluorophore-Assisted Carbohydrate Electrophoresis: Implications For Extracellular Glucose And Intracellular Mannose-6-Phosphate" The Journal Of Biological Chemistry, 280:17901-17909, 2005
Shang, J., Gao, N. Kaufman, R. J., Ron, D., Harding, H.P., and Lehrman, M.A., "Translational Balancing By The eIF2alpha Kinase PERK Couples ER Glycoprotein Synthesis To Lipid-linked Oligosaccharide Flux" Journal of Cell Biology, 176:605-616, 2007
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