Date of Award
Fidalgo da Silva, Elizabeth
Cerebellum, Medulloblastoma, TSC1, TSC2, Tuberin
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Mutations in the TSC2 gene, coding for the tumour suppressor protein Tuberin, lead to formation of benign tumours in systems like the brain. Some data supports Tuberin being an essential regulator of neural development and playing a role in cell fate decisions. I hypothesized that Tuberin is an essential regulator of neural cell fate decisions in the cerebellum and mutations in Tuberin may fuel the expansion of a stem-like population of cells in the childhood malignant brain cancer Medulloblastoma (MB). I found that Tuberin levels were tightly regulated in select regions of the brain. Culture of primary cerebellum stem/progenitor cells was performed. I demonstrated that Tuberin levels are downregulated throughout cell differentiation. Tuberin levels are high in the stem-like population in MB cells. This supports that Tuberin is an essential regulator of differentiation in stem-like progenitor population. Coaxing this stem-cell population to undergo functional differentiation in MB is one potentially exciting area for new cancer therapy.
Abu Khatir, Bashaer, "TUBERIN REGULATION IN NEURAL TISSUE AND CELL FATE" (2016). Electronic Theses and Dissertations. 5624.