Design and clinical applications of protease-activated optical chemical probes
Abstract/Contents
- Abstract
- Tumor resection remains one of the best ways to ensure a positive outcome for cancer patients. Intraoperative differentiation between tumor and healthy tissue is critical and tools that can aid surgeons make these important surgical decisions are being pursued in various biomedical/engineering disciplines. Here, I describe chemical tools that are designed to sense the tumor microenvironment, activate in the tumors, and produce an observable signal, thus allowing for surgical margin detection. Proteases are enzymes that hydrolyze peptide bonds and play key roles in normal physiology as well as in disease. In cancer, tumor-associated macrophages, which are immune cells, release various proteases which cleave molecules used for signaling, tissue repair, angiogenesis, and degrade the extra-cellular matrix. While there are methods to analyze protease mRNA and protein levels, they do not reflect the proteolytic activity of the cancer micro-environment. Using fluorescently-quenched optical chemical probes, we are able to dynamically monitor this protease activity. This work is broadly divided into two parts: 1) Clinical applications of optical chemical probes for imaging disease and 2) Design strategies of protease-activated optical chemical probes. Chapters 2-4 describe how clinical considerations guided us to optimize chemical probes to be compatible with imaging equipment used in the clinic. We find that these optical chemical probes augment surgical workflows in the operating room and enhance pathology analyses, allowing clinicians to make more accurate diagnoses. In Chapter 6, we discuss the development of protease-activated chemical probes by directly screening tumor samples. This unbiased approach allows us to design chemical tools that responds more accurately to the complex milieu of proteolytic activity found in actual tumor microenvironments
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 | Yim, Joshua |
|---|---|
| Degree supervisor | Bogyo, Matthew, 1971- |
| Thesis advisor | Bogyo, Matthew, 1971- |
| Thesis advisor | Chen, James |
| Thesis advisor | Grimes, Kevin |
| Thesis advisor | Rosenthal, Eben |
| Degree committee member | Chen, James |
| Degree committee member | Grimes, Kevin |
| Degree committee member | Rosenthal, Eben |
| Associated with | Stanford University, Department of Chemical and Systems Biology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Joshua J. Yim |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Joshua Yim
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...