Characterization of a novel OTX2-driven stem cell program in group 3 and group 4 medulloblastoma
| dc.contributor.author | Stromecki, Margaret | |
| dc.contributor.examiningcommittee | Nachtigal, Mark (Biochemistry and Medical Genetics) Hannila, Sari (Human Anatomy and Cell Science) | en_US |
| dc.contributor.supervisor | Werbowetski-Ogilvie, Tamra (Biochemistry and Medical Genetics) | en_US |
| dc.date.accessioned | 2017-08-30T15:21:50Z | |
| dc.date.available | 2017-08-30T15:21:50Z | |
| dc.date.issued | 2017 | |
| dc.degree.discipline | Biochemistry and Medical Genetics | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Medulloblastoma (MB) is a primary pediatric brain cancer that is frequently accompanied by metastasis and poor long-term prognosis. Our goal is to identify new signaling pathways that regulate the treatment-resistant MB cellular phenotypes, namely the stem cells. The OTX2 gene, which is amplified or overexpressed in the majority of Group 3 and 4 MBs, is a central regulator of stem cell function in these tumors. Here, we characterized the OTX2 regulatory network and identified a negative correlation between OTX2 and axon guidance genes in Group 3 and 4 MB stem/progenitor cells and tumors. Functional validation studies demonstrated that increased levels of semaphorin 4D (SEMA4D), L1 Cell Adhesion Molecule (L1CAM), and neuropilin-1 (NRP1) are associated with decreased self-renewal and that the downstream RHO signaling may be contributing to these effects. Our results offer critical insights into the molecular drivers of these aggressive tumors and provide a framework to pursue novel therapies. | en_US |
| dc.description.note | October 2017 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/32396 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Medulloblastoma, cancer stem cells, OTX2, axon guidance genes, semaphorin, Rho | en_US |
| dc.title | Characterization of a novel OTX2-driven stem cell program in group 3 and group 4 medulloblastoma | en_US |
| dc.type | master thesis | en_US |