Spy1-Mediated Cell Cycle Effects Enhance Oncogenic Transformation by Selected Drivers in Human Glioblastoma
Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Challenges Theme
Open Challenge
Faculty Sponsor
Dr. Lisa Porter
Proposal
Development of the central nervous system is an intricate process requiring cellular events to coordinate with one another to create a fully functional and adequately structured brain. A small population of adult neural stem cells (NSCs) resides in the mammalian brain and aids neurogenesis throughout life. Cell cycle regulation plays a vital role in determining the fate of NSCs in the adult brain and maintaining a crucial balance between self-renewal and differentiation. Using an inducible, conditional transgenic mouse model, our group has demonstrated that driving the expression of the atypical cyclin-like protein Spy1 in the NSC population in the brain inhibits differentiation and promotes self-renewal. The current study investigates the role of Spy1-mediated effects in tumorigenesis in the face of aberration in selected tumour suppressors and oncogenes known to drive glioblastoma. Using the transgenic mouse model, we analyze the cooperation between Spy1 and the designated drivers p53, PTEN, c-Myc, and EZH2 with respect to their expression, localization, and role in self-renewal and stemness in NSCs. This study will elucidate whether Spy1-mediated cell cycle regulation can enhance potential aberrant regulation in NSCs. The results will contribute to the development of new therapeutics to target and treat GBM, improving patient outcomes and enhancing population well-being in future generations.
Grand Challenges
Viable, Healthy and Safe Communities
Spy1-Mediated Cell Cycle Effects Enhance Oncogenic Transformation by Selected Drivers in Human Glioblastoma
Development of the central nervous system is an intricate process requiring cellular events to coordinate with one another to create a fully functional and adequately structured brain. A small population of adult neural stem cells (NSCs) resides in the mammalian brain and aids neurogenesis throughout life. Cell cycle regulation plays a vital role in determining the fate of NSCs in the adult brain and maintaining a crucial balance between self-renewal and differentiation. Using an inducible, conditional transgenic mouse model, our group has demonstrated that driving the expression of the atypical cyclin-like protein Spy1 in the NSC population in the brain inhibits differentiation and promotes self-renewal. The current study investigates the role of Spy1-mediated effects in tumorigenesis in the face of aberration in selected tumour suppressors and oncogenes known to drive glioblastoma. Using the transgenic mouse model, we analyze the cooperation between Spy1 and the designated drivers p53, PTEN, c-Myc, and EZH2 with respect to their expression, localization, and role in self-renewal and stemness in NSCs. This study will elucidate whether Spy1-mediated cell cycle regulation can enhance potential aberrant regulation in NSCs. The results will contribute to the development of new therapeutics to target and treat GBM, improving patient outcomes and enhancing population well-being in future generations.