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Modeling Aggressive Medulloblastoma Using Human Induced Pluripotent Stem Cells

Principal Investigator:
Mingyao
Ying

Brain tumors are the most common cause of childhood oncological death, and medulloblastoma (MB) is the most common malignant pediatric brain tumor. Group 3 MB is characterized by amplification and overexpression of oncogenic transcription factor MYC, herein referred to as MYC-driven MB. Modeling MYC-driven MB is critical for developing and testing potential therapies for this highly aggressive MB. The General Hypothesis of this study is that MYC transforms human-iPSC-derived neural stem cells and neuronal precursor cells, and drives the formation of aggressive MB lesions in mice, which recapitulate human group 3 MYC-driven MB.

  1. Aim 1. To establish a human-iPSC-derived MYC-driven MB model and test the effects of Atoh1 expression on tumor initiation and growth in this MB model.
  2. Aim 2. To identify the genome-wide MYC-regulated transcriptional network responsible for MYC-driven tumorigenesis, and to determine the effects of Atoh1 expression on MYC-regulated transcriptional events.

If successful, we will establish for the first time a human-iPSC-derived tumor model for the most aggressive subgroup of human MB and further use this model to identify the MYC-regulated transcriptional network essential for MB tumorigenesis.

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