Research / Clinical
Summary
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Diseases/Research Topics
Control of Differentiation and Development, Differentiation, Glycoimmunology
Research in our laboratory is focused upon investigating the function of members of the glycosyltransferase gene superfamily in mammalian ontogeny, physiology, and disease etiology. More than 1% of the mammalian genome encodes enzymes that participate in carbohydrate (also termed glycan)-based post-translational protein modifications in the Golgi. These reversible modifications function among extracellular compartments in analgous manner as phosphorylation functions inside the cell to control signal transduction and metabolism.
Our research involves the use of homologous recombination in embryonic stem cells followed by the production and analysis of genetically altered mice bearing germline lesions in specific glycosyltransferases. We also employ a technique developed by this laboratory allowing gene lesions to be relegated to specific tissues and cell types by use of conditional mutagenesis involving the Cre-loxP recombination system.
Research in this lab has demonstrated that glycan structures provide various functions in the developing embryo, including the derivation of left-right asymmetry, neural tube formation, and vascularization. More recently we have found that specific glycosyltransferases and their glycan linkages formed regulate B lymphocyte signal transduction, erythropoiesis, T cell and platelet homeostasis, blood coagulation governed by von Willebrand's factor, autoimmune disease pathogenesis, and cell-type-specific functional segregation of vascular inflammation.
In the last few years, an exponential increase in the clinical diagnosis of carbohydrate-based genetic diseases, such as the Carbohydrate Deficient Glycoprotein Syndromes, have been noted in the liteature. We have begun to model such diseases in the mouse to acquire a greater understanding of how glycosyltransferase dysfunction leads to disease pathologensis and to provide possible therapeutic approaches.
Keywords: genetics, molecular biology, glycobiology, immunology, developmental biology, pharmacology, physiology, neurobiology
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