Enzymatic and imaging based approaches to study the mammalian glycocalyx
Abstract/Contents
- Abstract
- Every cell in the human body is coated with a peripheral layer of glycosylation. These polysaccharides, glycoproteins, glycolipids, and proteoglycans organize into an extramembrane compartment termed the glycocalyx. The glycocalyx is the cell's first point of contact with the extracellular environment, and is a key regulator of cell-matrix and cell-cell interactions. Investigations into the architecture and dynamics of the glycocalyx stand to benefit from methods to (i) spatially classify glycans at relevant length scales, and (ii) selectively edit glycocalyx components. After an introductory Chapter 1, Chapter 2 describes a super-resolution microscopy based approach for quantification of glycocalyx parameters. Application of this method in the context of pancreatic cancer revealed that oncogenic KRAS changes the glycocalyx in part by promoting the biosynthesis of mucins. Mucins are a class of cell surface glycoprotein that are difficult to study and drug due to their dense glycosylation and resistance to proteases. Chapter 3 describes characterization of a mucin-selective protease derived from the human gut microbiome, which enables selective cleavage and release of mucins from live cells. This tool lowers barriers to the study of native mucin biology and represents a potential strategy for therapeutic intervention in mucin-expressing cancers. Chapter 4 describes unbiased screening in search of mammalian enzymes that proteolyze mucin domains, culminating in the observation that the human lysosomal protease cathepsin D exhibits such activity. The discovery that a human protease cleaves mucin domains without prior deglycosylation has implications for our basic understanding of human mucin catabolism and the consequences when it goes awry.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Pedram, Kayvon |
|---|---|
| Degree supervisor | Bertozzi, Carolyn R, 1966- |
| Thesis advisor | Bertozzi, Carolyn R, 1966- |
| Thesis advisor | Cui, Bianxiao |
| Thesis advisor | Felsher, Dean (Dean Walton) |
| Degree committee member | Cui, Bianxiao |
| Degree committee member | Felsher, Dean (Dean Walton) |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Kayvon Pedram. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Kayvon Pedram
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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