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Profiling and modulating sialylation and desialylation of monocytes and macrophages and their functions

Zhao, Yu
http://orcid.org/0000-0001-6689-3700
http://rave.ohiolink.edu/etdc/view?acc_num=csu1631458296896894

Abstract Details

2021, Doctor of Philosophy in Clinical-Bioanalytical Chemistry, Cleveland State University, College of Sciences and Health Professions.
Macrophages are versatile cells that take part in many physiological and pathological processes, such as immune response, inflammation and tissue injury and repair. Macrophages cell surface expresses a dense layer of glycans often terminated with sialic acids (Sias), which are critical mediators of cell-cell, cell-ligand, and cell-pathogen interactions and thus contribute to both health and disease. However, exactly how cell surface glycans and their variety and variability contribute to specific physiological or pathological pathways remains poorly defined. Sias are acidic monosaccharides and terminate cell surface glycans in different linkages and levels, known as sialylation status that impacts the cell properties and represents different cellular statuses. Cell surface Sias are often the fundamental determinants for immune receptors, such as for Selectins and Siglecs-mediated immune functions. Therefore, systematic profiling and modulating of cell surface sialylation status (Sia levels and linkages) of macrophages are very important for understanding macrophage cell surface glycans’ structures and functions related to macrophage diversity, phenotypes, and functions. In addition, they will contribute to discovering novel mechanisms and approaches for disease diagnosis and treatment. In this dissertation study, three specific projects were conducted: (1) profiling cell sialylation status of monocyte and macrophages under different conditions; (2) modulating cell surface sialylation status by inhibiting desialylation pathway of macrophages and evaluate the inhibition consequence on macrophage functions; (3) re-engineering cell surface sialylation status of macrophages via metabolic engineering and evaluate the re-engineering consequence on macrophage functions. The LC-MS/MS was used to quantify the amount of Sias and related sialylation and desialylation levels. Western blot was used to qualify the protein level. Confocal images were used to profile and quantify sialylation levels and phenotype, and functions of macrophages. Overall, a systematic recognition and modulation of sialylation and desialylation related to cellular property and function of macrophages will contribute to understading specific signaling pathways in macrophages related to both physiological and pathological pathways and defining the phenotypes and elucidate functional diversity of macrophages. Further, it will provide novel mechanisms and approaches for diseases diagnosis and treatment.
Xue-Long Sun (Committee Chair)
David Anderson (Committee Member)
Aimin Zhou (Committee Member)
Chandrasekhar Kothapalli (Committee Member)
Baochuan Guo (Committee Member)
Chemistry

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Citations

  • Zhao, Y. (2021). Profiling and modulating sialylation and desialylation of monocytes and macrophages and their functions [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1631458296896894

    APA Style (7th edition)

  • Zhao, Yu. Profiling and modulating sialylation and desialylation of monocytes and macrophages and their functions. 2021. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1631458296896894.

    MLA Style (8th edition)

  • Zhao, Yu. "Profiling and modulating sialylation and desialylation of monocytes and macrophages and their functions." Doctoral dissertation, Cleveland State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=csu1631458296896894

    Chicago Manual of Style (17th edition)

csu1631458296896894
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© 2021, some rights reserved.Creative Commons License Profiling and modulating sialylation and desialylation of monocytes and macrophages and their functions by Yu Zhao is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Cleveland State University and OhioLINK.