Friday, May 9, 2025
5/9/2025
Characterizing extracellular glycoproteins and unraveling their functions - Abstract Proteins on the cell surface and in the secretome play extremely important roles in nearly every extracellular event from cell-cell communication to cell response to environmental changes. Almost all of them are glycosylated, and aberrant expression and interactions of extracellular glycoproteins are directly related to human diseases such as cancer. Both the protein part and the glycan component contain much valuable information about cellular developmental and diseased statuses. Secreted glycoproteins in the bodily fluids provide an excellent non-invasive source for disease early detection, and besides serving as biomarkers, surface glycoproteins are often drug targets, especially for macromolecular drugs such as antibodies and enzymes. Comprehensive characterization of extracellular glycoproteins can help better understand protein functions, cellular activities, and disease mechanisms. However, it is extremely challenging because of the low abundances of many glycoproteins, the high diversity of glycans, and the complexity of biological samples. Besides these challenges, the methods are required to selectively separate glycoproteins on the cell surface or in the secretome prior to mass spectrometric analysis. Furthermore, the interactions between surface glycoproteins and secreted ones are essential for cell-cell communication and cell immune response, but remain to be explored. There is an urgent need to develop innovative methods to systematically study extracellular glycoproteins and their interactions. Based on extensive research experience with mass spectrometry (MS)-based glycoproteomics, novel and effective methods will be developed to comprehensively analyze glycoproteins on the cell surface and in the secretome. Furthermore, a new and integrative method will be developed to systematically investigate the interactions between surface glycoproteins and secreted ones from other cells, which will provide unprecedented and valuable information, including identifying new ligands for orphan receptors and discovering novel interactions between surface proteins and secreted ones. Additionally, the regulation of glycans on the interactions among extracellular glycoproteins will also be studied. These methods will be applied to study extracellular glycoproteins and their interactions in different types of immune cells with bacterial or viral infection. Considering the importance of extracellular glycoproteins, the proposed methods in this project will have extensive applications in the biological and biomedical research fields.
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