Dissecting the Heterogeneous Nature of Brain Tumours
Standing
Undergraduate
Type of Proposal
Oral Presentation
Faculty
Faculty of Science
Proposal
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumour with 5-year survival rates of less than 10%. Past literature contends that select cell populations exist within the tumour mass that drive GBM growth. These populations are referred to as Brain Tumour Initiating Cells (BTICs). While the true origin of these cells is debatable, physiologically these cells possess immature properties of normal neural stem cells. They are highly resistant to drug treatment, radiation and form tumours at a high rate when transplanted into mice. The complexity of GBM is elevated due to the fact that not all tumour masses are the same. Most patient tumours can be categorized into three specific subtypes based on their genetics. Additionally, Spy1 is a unique cell cycle regulator that is found in normal neural stem cells during brain development; however, during rapid cancerous growth Spy1 is present in high levels and allows progress through the cell cycle without halting at the traditional checkpoints. I hypothesize that Spy1 plays a unique role in expansion of specific BTIC populations. Pinpointing which of those populations are responsible for GBM progression and therapy resistance would be of utmost value and Spy1 may be a pivotal target. We will sort patient derived brain tumour cultures via fluorescence activated cell sorting (FACS) to enrich for well characterized BTIC cell surface markers. Emerging populations will be characterized in vitro and in vivo for their proliferation, tumourigenicity and drug resistance potential. In addition, to address the essentiality of Spy1, we will manipulate its levels in selected BTIC populations and assess the impact on established BTIC characteristics. This project will not only contribute to better understanding of the heterogenous nature of GBM but will also set a potential direction for assessment of new therapy targets and effective treatment strategies against brain tumours.
Grand Challenges
Healthy Great Lakes
Dissecting the Heterogeneous Nature of Brain Tumours
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumour with 5-year survival rates of less than 10%. Past literature contends that select cell populations exist within the tumour mass that drive GBM growth. These populations are referred to as Brain Tumour Initiating Cells (BTICs). While the true origin of these cells is debatable, physiologically these cells possess immature properties of normal neural stem cells. They are highly resistant to drug treatment, radiation and form tumours at a high rate when transplanted into mice. The complexity of GBM is elevated due to the fact that not all tumour masses are the same. Most patient tumours can be categorized into three specific subtypes based on their genetics. Additionally, Spy1 is a unique cell cycle regulator that is found in normal neural stem cells during brain development; however, during rapid cancerous growth Spy1 is present in high levels and allows progress through the cell cycle without halting at the traditional checkpoints. I hypothesize that Spy1 plays a unique role in expansion of specific BTIC populations. Pinpointing which of those populations are responsible for GBM progression and therapy resistance would be of utmost value and Spy1 may be a pivotal target. We will sort patient derived brain tumour cultures via fluorescence activated cell sorting (FACS) to enrich for well characterized BTIC cell surface markers. Emerging populations will be characterized in vitro and in vivo for their proliferation, tumourigenicity and drug resistance potential. In addition, to address the essentiality of Spy1, we will manipulate its levels in selected BTIC populations and assess the impact on established BTIC characteristics. This project will not only contribute to better understanding of the heterogenous nature of GBM but will also set a potential direction for assessment of new therapy targets and effective treatment strategies against brain tumours.