Design and clinical applications of protease-activated optical chemical probes

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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


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


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.


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

© 2020 by Joshua Yim
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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