Post-doctoral Fellowship Grant Awarded to Zach Reitman

Diffuse intrinsic pontine glioma (DIPG) is a devastating childhood brain tumor. DIPG always grows back after
radiation therapy, and there is no effective chemotherapy for DIPG. We recently discovered that about 20% of
DIPGs have a mutation in a gene called PPM1D within the tumor tissue. We believe that the PPM1D mutation
helps DIPGs to grow, and that it also helps the tumor to resist radiation treatment.
We predict that drugs which target the PPM1D mutation could help to cure DIPGs. The first step in
testing our prediction is to study growing tumor tissue derived from human DIPGs that have the PPM1D
mutation. We will test whether genetic engineering of PPM1D, or chemicals that target PPM1D, can kill these
tumor tissues when they are grown in petri dishes or in the brains of mice. This will determine whether drugs
that target PPM1D will be useful treatments for children with DIPG. As there are no PPM1D inhibitor drugs
available in the clinic today, these results are critical to determine if PPM1D inhibitors should be pursued for
drug development and clinical trials.
We also want to learn how the PPM1D mutation causes radiation resistance in DIPG. To do so, we will
perform experiments to identify the most important structures within the PPM1D gene. This will allow us to test
whether therapies aimed at those important areas within PPM1D could also be useful as new treatments for
DIPG.