Research And Grants

Using Zebrafish to Accelerate DIPG Drug Development.

A critical barrier to improvements in diffuse intrinsic pontine glioma (DIPG) therapy is a lack of new drugs that have a broad therapeutic index. In DIPG, validation of new therapeutics is hampered by the long time (6 months) that most human DIPG tumors take to kill mice. This means that it can take 9-12 months to complete an efficacy study of a single candidate drug. To address this bottleneck, in collaboration with the laboratory of Dr. Jeffrey Mumm, who is an expert in zebrafish development, we have established human DIPG orthotopic xenografts in zebrafish. Because these fish are tiny, yet have central nervous systems analogous to those of humans, and are translucent, we can monitor the fluorescently-tagged human cells in real time as they grow and migrate in the developing fish. We have already established that our human DIPG cells to live and invade through the fish brain for up to five days, and we propose to further validate these studies, focusing on injecting zebrafish embryos with human cells to facilitate the use of these fish for rapid drug screening. Successful completion of this project will allow us to bypass one of the major impediments to progress in DIPG therapy.