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The Phoenix lab generates and utilizes novel brain tumor model systems.
We use these brain tumor models to investigate a wide range of areas that include:
(1) Determining the function of genetic alterations identified in brain tumors. Key studies that sequence the DNA of brain tumor samples from patients have identified genetic alterations / mutations in cancer cells. Leveraging our brain tumor models system we examine how these mutations contribute to brain tumor formation and growth. Learning about how individual mutations function, or how several different mutations can cooperate with each other in unique ways, provides new opportunities to develop strategies that target these underlying mechanisms.
(2) Identifying vulnerabilities of brain tumors and preclinical therapeutic studies. Our brain tumor modeling system provides several opportunities to test and identify new therapies. First, we can develop isogenic brain tumor models (meaning they vary by one different genetic mutation) so we can test whether genetic differences found in patients results in selective vulnerabilities. Second, our models provide an in vivo system to study how tumor cells interact with all the other cell types in the brain. This includes blood vessels (which are important for systematic delivery of drugs), neurons (which can communicate with tumor cells), and immune cells. Having models to accurately determine whether drugs penetrate into brain tumors and show activity is essential to translate experimental therapies into the clinic. We aim to continue applying our model system to identify new and better therapeutic modalities.
(3) Building new brain tumor models. We have published several models of pediatric brain tumors, including Diffuse Intrinsic Pontine Glioma (DIPG; also known now as Diffuse Midline Glioma or DMG) and pediatric High-Grade Glioma (pLGG). These models serve as important systems to unravel features of tumor biology and tools for preclinical therapeutic studies. Recognizing that there are subtypes of pediatric and adult brain tumors that lack available models, we are carrying out experiments to create new brain tumor models for the research community.
(4) Sharing brain tumor models. In addition to building primary brain tumor models, we have also established cell lines from these models that can be re-implanted back into immune competent models. Since cell-based implant experimental models are widely used by labs around the world, it provides a system for other researchers to explore their treatment(s) of interest. Because these models are fully immune competent, many labs are utilizing these models to test novel treatments like immunotherapies. We have shared these tools with labs around the world, including in the USA, Europe, and Australia.
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