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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.

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.
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. 

Kennedy Krieger Institute Announces Retirement of President and CEO

Dr. Gary W. GoldsteinThe Institute’s board of directors is conducting a national search and is expected to name a new CEO in the coming months.
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