A Precise Look at Tumor Behavior

THE TISSUE THAT MAKES UP BRAIN TUMORS is very complex. It’s not easy for scientists to look at tumor cells all at once and figure out what’s happening in the tumor. But discovering better, more precise ways to look at these cells and their genetic makeup holds promise for faster diagnoses and better treatments.

Simon Gregory, Ph.D., and his team are using unique technologies to find better ways of looking at tumor cells. Gregory is director of the Section for Genomics and Epigenetics at the Duke Molecular Physiology Institute. He is also a professor in the Department of Neurology.

Previously, the researchers used bulk genomics to look at the cells. Essentially, they were trying to examine hundreds of thousands—sometimes millions—of cells at once. Gregory likens it to trying to understand which individual pieces of fruit have been blended into a smoothie by looking at the contents of the glass.

However, Tisch family funding has allowed Gregory’s lab to move to more precise methods, which permits them to do their work at the cellular and subcellular levels. The first platform looks at individual cells from tumor tissue. Researchers can create gene expression profiles from each cell from all genes that may be switched on or off that contribute to cancer development. With single-cell profiling, the researchers can look at up to 10,000 cells at one time and even define the types of immune cells or profile non-DNA-based mechanisms that cause genes to be expressed.

“Given that brain tumors are a mix of lots of different cells doing different things at the same time, by breaking it down and then independently assembling them, you’re able to generate an idea of what the cells are doing,” Gregory says.

“Because we’re looking at the gene expression profiles, we can figure out what pathways the cells activate. And by doing that, you can start developing means of identifying novel therapies by understanding these activated pathways.

Gregory’s team is beginning to use a second technology capable of profiling gene expression at subcellular levels. While the single cell tool is excellent for gene discovery, the molecular profiling tool of target genes allows researchers to look at gene expression at extremely high resolution to start building a picture of how cancer affects the function of particular cell types and how they interact. Duke would be one of the first medical centers in the world to use this technology to analyze brain tumors. Potentially, pathologists could use the Gregory lab’s assays as an early diagnostic tool for brain cancer. In addition to potentially leading to better outcomes for patients with brain tumors, the lab’s work with molecular profiling could have significant implications for the future of brain tumor research.