Title

The role of cooperating mutations in Spy1 mediated expansion of Brain Tumour Initiating Cells

Standing

Undergraduate

Type of Proposal

Oral Research Presentation

Challenges Theme

Open Challenge

Your Location

University of Windsor

Faculty

Faculty of Science

Faculty Sponsor

Lisa Porter

Abstract/Description of Original Work

Limitation in treatment of Glioblastoma multiforme (GBM), the most aggressive type of brain tumour, is characterized by the extreme genetic and phenotypic heterogeneity observed not only between individual patients, but also within a single tumour mass. It has been demonstrated that populations of very immature stem- like Brain Tumour Initiating Cells (BTICs), contribute not only to the heterogeneity but also to the therapy resistance of GBM. Speedy (SPY1; SPDYA) is an unusual cell cycle protein that has been shown to promote proliferation, stem cell self-renewal and expansion of TIC in GBM. Amplification of Spy1 locus was found to correlate with poor GBM patient prognosis. In our lab, we engineered a novel mouse model, termed NTA-Spy1, to overexpress Spy1 specifically in populations of normal neural stem cells. We demonstrated that NTA-Spy1 cells, in combination with inhibition of tumour suppressors such as p53 and/or PTEN, not only possess an increase in stem cell marker expression but also demonstrate oncogenic transformation in vitro. My project will investigate the biology of NTA-Spy1 cells upon tumour suppressor depletion in vivo using Zebrafish xenograft model. I will study and characterize potential tumour foci formation. BTIC composition and therapy resistance of manipulated NTA-Spy1 cells will be addressed in vitro. This project will aid in further understanding of the role of Spy1 in brain tumourigenesis which can be implemented into discovery of novel targeted therapies directed against GBM.

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The role of cooperating mutations in Spy1 mediated expansion of Brain Tumour Initiating Cells

Limitation in treatment of Glioblastoma multiforme (GBM), the most aggressive type of brain tumour, is characterized by the extreme genetic and phenotypic heterogeneity observed not only between individual patients, but also within a single tumour mass. It has been demonstrated that populations of very immature stem- like Brain Tumour Initiating Cells (BTICs), contribute not only to the heterogeneity but also to the therapy resistance of GBM. Speedy (SPY1; SPDYA) is an unusual cell cycle protein that has been shown to promote proliferation, stem cell self-renewal and expansion of TIC in GBM. Amplification of Spy1 locus was found to correlate with poor GBM patient prognosis. In our lab, we engineered a novel mouse model, termed NTA-Spy1, to overexpress Spy1 specifically in populations of normal neural stem cells. We demonstrated that NTA-Spy1 cells, in combination with inhibition of tumour suppressors such as p53 and/or PTEN, not only possess an increase in stem cell marker expression but also demonstrate oncogenic transformation in vitro. My project will investigate the biology of NTA-Spy1 cells upon tumour suppressor depletion in vivo using Zebrafish xenograft model. I will study and characterize potential tumour foci formation. BTIC composition and therapy resistance of manipulated NTA-Spy1 cells will be addressed in vitro. This project will aid in further understanding of the role of Spy1 in brain tumourigenesis which can be implemented into discovery of novel targeted therapies directed against GBM.