Rational and combinatorial engineering of the met and axl receptor systems
Abstract/Contents
- Abstract
- Ligand-receptor interactions govern nearly all cellular processes, and dysregulation leads to a range of diseases including cancer, autoimmune diseases, and regenerative disorders. As such, new strategies to target ligand-receptor interactions for therapeutic applications are an important area of research. To develop enhanced agonists and antagonists of the Met receptor, a critical target in cancer therapy and regenerative medicine, we engineered a fragment of the natural activating ligand (termed NK1). First, NK1 was evolved for improved stability using directed evolution. Then, using the activation mechanism of Met by NK1, the resulting enhanced stability mutants were rationally engineered for either agonistic or antagonistic activity. Next, the rationally engineered mutants were used as 'molecular tools' to provide further insights into NK1 structure and function. Finally, these insights supported additional rational engineering to generate further enhanced agonistic proteins. The antagonistic and agonistic proteins developed in this thesis hold promise as cancer therapeutics and diagnostics or for regenerative medicine applications, respectively. This work also supports native ligands as a promising starting point for development of therapeutic proteins.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Copyright date | 2011 |
| Publication date | 2010, c2011; 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Jones, Douglas Scott II |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Cochran, Jennifer R |
| Thesis advisor | Cochran, Jennifer R |
| Thesis advisor | Giaccia, Amato J |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Thesis advisor | Swartz, James R |
| Advisor | Giaccia, Amato J |
| Advisor | Khosla, Chaitan, 1964- |
| Advisor | Swartz, James R |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Douglas Scott Jones, II. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2011. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Douglas Scott Jones II
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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