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Modeling Aggressive Medulloblastoma Using Human Induced Pluripotent Stem Cells

Principal Investigator:

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.

Bradley L. Schlaggar, M.D., Ph.D., Named President and CEO of Kennedy Krieger Institute

We’re thrilled to welcome Bradley L. Schlaggar, M.D., Ph.D., to the Kennedy Krieger family as our next President and CEO.
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