Exploring connections at the mammalian cell surface
Abstract/Contents
- Abstract
- Monoclonal antibodies have become powerful tools for biomedical research and cancer therapy. However, identifying the precise molecular targets of monoclonal antibodies can be challenging. This thesis leverages emerging techniques in proteomics and genome editing to elucidate the targets of two clinically relevant monoclonal antibodies. First, we re-evaluate putative RNA binding by galectin-3 using CRISPR-mediated gene knockouts and endogenous epitope tagging. We demonstrate that previously reported RNA interactions are likely an artifact resulting from cross-reactivity with the RNA-binding protein hnRNPA2B1. Our findings refute direct RNA binding by galectin-3 in HeLa, underscoring the need for stringent controls when characterizing antibody targets. Next, we uncover the molecular identity of the cryptic tumor-associated antigen TAG-72 after decades of uncertainty. We identify the mucin protein MUC2 as a dominant TAG-72 carrier in colon cancer cells. Further analysis defines TAG-72 as aberrantly glycosylated sialyl-Tn pattern on select mucin-like domains. By integrating cutting-edge proteomic and genomic techniques, this thesis provides molecular insight into two clinically important monoclonal antibody targets. Our strategy of leveraging emerging technologies to characterize antibody epitopes could be widely applied to clarify other enigmatic biomarker interactions relevant to medicine and biology.
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 | 2024; ©2024 |
| Publication date | 2024; 2024 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Peltan, Egan Lee |
|---|---|
| Degree supervisor | Bertozzi, Carolyn R, 1966- |
| Thesis advisor | Bertozzi, Carolyn R, 1966- |
| Thesis advisor | Long, Jonathan Z |
| Thesis advisor | Martinez, Nicole M |
| Thesis advisor | Wysocka, Joanna, Ph. D. |
| Degree committee member | Long, Jonathan Z |
| Degree committee member | Martinez, Nicole M |
| Degree committee member | Wysocka, Joanna, Ph. D. |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Chemical and Systems Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Egan Peltan. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Thesis Ph.D. Stanford University 2024. |
| Location | https://purl.stanford.edu/gp242dd5944 |
Access conditions
- Copyright
- © 2024 by Egan Lee Peltan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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