ABTA

The Gene Whisperer

William Flavahan, PhD sees a bright future for brain tumor research.

It’s early in the morning, but Postdoctoral Research Fellow William Flavahan, PhD at the Broad Institute of MIT Bernstein Lab at Massachusetts General Hospital and Harvard Medical School is energized.

Despite being up overnight to care for his five-month-old daughter, this dedicated new father is also focused and attentive to other beings. Cancer cells to be exact. One could even call him “the gene whisperer.”

Dr. Flavahan, a former recipient of the American Brain Tumor Association’s grant program, focuses his postdoctoral work on epigenetics—the study of inheritable changes that do not affect the DNA sequence, but influence gene expression, which may contribute to the development of cancerous brain tumors such as glioblastoma.

To understand epigenetics, Dr. Flavahan uses a textbook analogy:

“If the DNA is a cell’s textbook, containing all the instructions it needs to fulfill any role in the body, then the epigenetics are the highlighter marks, folded pages, and post-it notes that the cells use to mark which parts of the DNA are important, and which aren’t,” he explains.

Dr. Flavahan started his doctoral work at the Cleveland Clinic, studying how certain cells within a single tumor (cancer stem cells) could grow better and be more resistant to drugs than the rest of the tumor cells. These cells also had the ability to grow in parts of the tumor that had very little nutrients.

I really don’t think there is a bigger clinical problem today than brain cancer.​

“Through my research at Cleveland Clinic, I discovered that part of the reason these cells were able to grow is that they had a turbocharged system of pulling nutrients in from the surroundings through expression of a protein called GLUT3,” Dr. Flavahan said.

How these cancer stem cells had the exact same genetic background as the rest of the tumor, but could have such different properties, intrigued him. “The standard view in the field had been that genetic changes are what make cancer cells so different,” he said. His research showed that while cancer stem cells and the rest of the tumor cells had the same genetic changes, the cancer stem cells had a completely different set of epigenetic marks—or instructions—allowing them to be much more aggressive.​

“What Flavahan’s work has taught us is that epigenetic controls can go awry and turn on oncogenes (a gene which in certain circumstances can transform a cell into a tumor cell) without any change in their DNA sequence,” said Bradley Bernstein, MD, PhD, director of the Broad Institute Epigenomics Program and professor of Pathology at Harvard Medical School. “It’s important because it suggests that an emerging class of drugs called ‘epigenetic’ therapies that target gene controls could be effective in these tumors.”

Dr. Flavahan’s research will be published in Nature showing that the same epigenetic markers common in gastric sarcoma in children are also common in certain types of glioma.

Dr. Flavahan believes there’s reason for hope as more of the science behind brain tumors is discovered. “The technology available for researchers is advancing at an exponential pace, so we’re able to create these central repositories of data, such as The Cancer Genome Atlas (TCGA), where cancer researchers across the country will make the data from deeply characterized tumor samples available to everyone. This really increases our research power by allowing the research community to discover connections between data that we wouldn’t have been able to see otherwise.”

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