Post-doctoral Fellowship Grant Awarded to Alan Jiao

Diffuse intrinsic pontine glioma (DIPG) is a deadly childhood brain tumor. Like many cancers, DIPG is caused by mutations – that is, changes in our DNA. However, unlike many cancers, ~80% of all DIPG tumors share the same exact mutation, one that is rarely found in other diseases and whose effects are poorly understood. Because this mutation is only present in tumor cells, and not in our normal cells, it is key to developing safe and effective drugs for treating DIPG. Our DNA can be thought of as an instruction manual for our cells, filled with annotations; the mutation in DIPG alters many of these annotations, and therefore, causes cellular instructions to be misinterpreted. This lies at the heart of how DIPG tumors are formed. The main goal of our research is to understand how we can block the effects of this mutation to help treat DIPG. To this end, we have created a new laboratory model to investigate (1) how the mutation causes changes in DNA annotations, and (2) how the correct annotations can be re-established. In conventional research models, only a few ways for blocking the effects of this mutation can be tested in a single experiment. In contrast, our model enables testing hundreds of millions of ways at the same time. Our system relies on the innovative use of genetic tools to systematically investigate how to most effectively block the effects of the mutation. Knowledge generated from our work will lay the foundation for designing new drugs for treating DIPG, and will be a valuable resource for the entire DIPG research community.