Towards engineering the human adaptive immune system : nucleic-acid-sequencing-based studies in health, disease and immunotherapy
Abstract/Contents
- Abstract
- The recent successes of cancer immunotherapy illustrate that long-intractable diseases can benefit from treatment approaches that focus on re-engineering aspects of the body's own defense system -- the immune system. The adaptive component of the immune system learns over time in response to external stimuli by a process of receptor evolution that can now be studied thanks to advances in high-throughput DNA sequencing. These advances also allow expression profiling of thousands of genes across thousands of individual cells at a time, facilitating the reconstruction of immune cell differentiation trajectories. The goal of my dissertation is to use these tools in order to gain a better understanding of systemic fallibilities of adaptive immunity -- which underlie the existence of deadly infections, autoimmune disease or cancer -- and to explore immunotherapies as a manner of engineering an improved immune system. First, I will elucidate age-related immune deterioration by analyzing the phylogeny of healthy elderly individuals' antibody repertoires, investigating the immunogenic challenges of influenza vaccination and chronic infection. Next, I will discuss the antibody repertoires of patients afflicted with a severe autoimmune disease, systemic-sclerosis-associated pulmonary arterial hypertension, a subset of whom received experimental suppressive immunotherapy with the B-cell depleting agent rituximab. I identified disease signatures at the molecular level and quantitatively modeled the process of reconstitution that follows B-cell depletion. Finally, I will expose the undesirable phenomenon of T-cell exhaustion in chimeric antigen receptor (CAR) T-cells designed for cancer immunotherapy. I characterized the basis of this phenomenon at the gene expression level so as to inform approaches of eliminating exhaustion by gene knock-out.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | de Bourcy, Charles |
|---|---|
| Associated with | Stanford University, Department of Applied Physics. |
| Primary advisor | Quake, Stephen Ronald |
| Thesis advisor | Quake, Stephen Ronald |
| Thesis advisor | Mackall, Crystal |
| Thesis advisor | Nicolls, Mark |
| Advisor | Mackall, Crystal |
| Advisor | Nicolls, Mark |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Charles de Bourcy. |
|---|---|
| Note | Submitted to the Department of Applied Physics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Charles Francois Aloyse de Bourcy
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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