Molecular Mechanisms of Neuronal Activity Mediated NF1 Optic Glioma Initiation
Abstract/Contents
- Abstract
- In pediatric brain tumors, a permissive tumor microenvironment is known to be central for promoting the proliferation of cancerous cells. While a great variety of cell types may occupy the tumor microenvironment, neurons have been shown to be essential components, where their activity increases growth of high-grade glioma tumors (Venkatesh et al., 2015). However, the relationship between neural activity and initiation of the tumor is not well understood. Currently, many forms of pediatric brain cancers are unamenable to many classes of therapeutics and current treatment strategies remain unsatisfactory. Neurofibromatosis Type 1 (NF1), a tumor predisposition syndrome, causes small tumors to develop which associate with nerves. Patients may also develop low-grade gliomas of the optic pathway, optic pathway gliomas (OPG), where retinal ganglion cells (RGCs) constitute the sole neuronal component. Using a mouse model of these NF1-OPGs as a platform, we can interrogate the mechanisms of initiation of these gliomas, as they relate to neural activity. By manipulating the light-induced activity of this visual pathway, this project helps characterize the relationship between neuronal activity and glioma initiation. Mice possessing mutations in Nf1 were sacrificed after tumor initiation and their optic chiasms were analyzed for tumor volume, cellular proliferation, among other molecular markers. We demonstrated that neuronal activity plays a central role in the initiation of these gliomas and that this initiation is mediated through the ADAM10/neuroligin-3 molecular pathway. This demonstrates a novel characterization of the mechanisms of glioma initiation, which could yield novel therapeutic strategies for these pediatric low-grade gliomas along with other neuroligin-3 mediated adult high-grade gliomas.
Description
| Type of resource | text |
|---|---|
| Date created | June 2021 |
| Date modified | December 5, 2022 |
| Publication date | November 5, 2021 |
Creators/Contributors
| Author | Hysinger, Jared |
|---|---|
| Degree granting institution | Stanford University, Department of Biology, 2021 |
| Thesis advisor | Monje, Michelle |
| Thesis advisor | McConnell, Susan |
Subjects
| Subject | Biology |
|---|---|
| Subject | pediatric brain tumor |
| Subject | neurofibromatosis type 1 |
| Subject | optic pathway glioma |
| Subject | glioma |
| Subject | NF1 |
| Subject | cancer |
| Subject | Neuroligin-3 |
| Genre | Text |
| Genre | Thesis |
Bibliographic information
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- License
- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
Preferred citation
- Preferred citation
- Hysinger, Jared and Monje, Michelle and McConnell, Susan. (2021). Molecular Mechanisms of Neuronal Activity Mediated NF1 Optic Glioma Initiation. Stanford Digital Repository. Available at: https://purl.stanford.edu/mm488pr3513
Collection
Undergraduate Theses, Department of Biology, 2020-2021
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- Contact
- jaredhys@stanford.edu
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