Research Information
Research Interests
Brain tumors can be among the most lethal cancers known, and are now the most frequent cause of cancer death in adolescents and young adults. Advanced brain tumors are driven by cancer stem cells and have extreme cellular diversity, with different independent tumor cell populations growing within distinct niche environments. This great diversity is part of the reason brain tumors are so difficult to treat. A brain tumor is therefore not just a mass of identical cancer cells, but rather a dynamic and diverse community of normal and cancer cell types functioning together in time and space. Many cancerous cells are so different from each other that their vulnerabilities must be discovered and attacked individually. We therefore believe the next evolution of brain cancer research will be driven by a more holistic recognition and understanding of the entire cell community present within tumors.
Our goal is to explore and exploit the unique biology of the different cell populations within brain tumors. We use advanced, 3-dimensional, and patient-direct (not just patient-derived) models to study the brain tumor cell community with single-cell resolution. Our novel 3D organoid cultures, or “mini-tumors”, better recapitulate the diversity and microenvironmental biology of human tumors than traditional cultures. We have developed ways to isolate and functionally test cells from spatially distinct niches, and have leveraged this capability to identify unique and non-overlapping cancer vulnerabilities in different cell populations growing together in a tumor. We are now combining this data with novel 3D small molecule screening to pair multiple niche-specific targets with drugs that effectively shut these targets down. This allows us to create rationally-designed combination therapies to more completely eradicate the disease.
To truly change the outcomes for brain tumor patients, we must improve our ability to faithfully model and retain the cellular behaviors found within patient tumors, and we must be able to study these interacting cell populations at a granular level. Our lab is therefore focused on
- Developing brain tumor models that better mimic tumors within patients
- Studying cell-cell and cell-environment interplay within tumor stem cell niches
- The specific targeting and destruction of individual cell populations within brain tumors
Research Projects
Our lab is focused on finding treatments for currently incurable advanced brain cancers. Part of the reason that advanced brain tumors are so hard to cure is that they contain many different kinds of cells in different locations working together to grow the tumor. Our usual lab models are grown on plastic and only represent a piece of all the cell types in a brain cancer. In a patient’s brain, cancer cells growing in different environments of the tumor can be so different from each other that we believe no one therapy will ever be able to kill them all.
We are attacking this disease by first preserving the diversity of cells present in patients using 3-dimentional “mini-tumors” that retain different tumor environments as found in patients. We then study the different kinds of tumor cells in 3D, dividing up the complex tumor into smaller groups that we can treat and kill. By separately targeting essential pieces of each separate type of tumor cells, we are able to more completely destroy the whole tumor. We believe this work critical to create new therapies that more successfully move from our laboratory models to our human patients.