The Developing Brain and Cancer

April 26, 2011
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Just a few decades ago, the connection between neurobiology and cancer biology was suspected, but unspoken.

“Today, it represents one of the most robust interfaces between basic neuroscience and clinical medicine,” said Anthony-Samuel LaMantia, Ph.D., professor of Pharmacology and Physiology in the GW School of Medicine and Health Sciences (SMHS) and founding director of the GW Institute for Neuroscience (GWIN), at the first annual Neuroscience Symposium, April 27.

The symposium, aptly titled “The Developing Brain and Cancer,” featured four leading researchers who highlighted the latest advances in the field of neuroscience that contribute to the understanding of how the brain develops, and how cancer can compromise the developing brain.

Held at the GW Marvin Center, the day-long event brought together close to 80 researchers, graduate students, and scientists, and was jointly sponsored by SMHS, the Office of the Vice President for Research, and the Columbian College of Arts and Sciences — the three entities that support GWIN.

Sally Moody, Ph.D., professor of Anatomy and Regenerative Biology in SMHS, delivered the first keynote address, which shed new light on the earliest stages of nervous system development.

“In all vertebrates, we have several steps that take you from the initiation of embryonic cells becoming neural to when you get actual, independent, specified kinds of neurons,” she explained.

Using her work with frog embryos as a guide, Moody hypothesized that the expression of FoxD4/5, one of the earliest genes in the network, plays a key role in neural stem cell fate, particularly through its activation of a group of genes called Sox.

The second keynote speaker was Michael Dyer, Ph.D., a member of St. Jude Children’s Research Hospital in the Department of Developmental Neurobiology, and co-leader of the Developmental Therapeutics for Solid Malignancies Program. Dyer discussed how his work studying retinoblastoma, a childhood cancer of the eye, has helped bridge the gap between developmental neurobiology and cancer genetics.

Among many influential discoveries, Dyer explained how his lab’s “unbiased” approach to studying tumor cells led to the unpredictable finding that adult neurons can divide without losing their distinctive features.

“What we’ve shown is that everybody was right over the years: these tumors have properties of different cell types.  It’s just that nobody considered the possibility that they were all the same cell,” Dyer said.

Vittorio Gallo, Ph.D., professor of Neuroscience at SMHS, director and Wolf-Pack Chair in Neuroscience at Children’s National Medical Center’s Center for Neuroscience Research, presented the third keynote address.

Gallo discussed how certain signaling pathways help to maintain the balance between specific types of neurons developed in the brain that are critical under both normal conditions and after injury. These pathways too, he explained, contribute to the growth and development of neural progenitor cells (NPCs), one of the groups of neurons. Because NPCs and these pathways may influence the formation of brain tumors, they are important to understand for potential clinical applications, Gallo pointed out.

Scott Loren Pomeroy, M.D., Ph.D., Bronson Crothers Professor of Neurology at Harvard Medical School and Neurologist-in-Chief at Children's Hospital Boston, delivered the final keynote address about Medulloblastoma, the most common type of malignant brain tumor in children.

Pomeroy explained how the reclassification of Medulloblastoma into various subtypes is leading to the creation of better targeted therapies. These therapies, he said, may not only improve survival, but they may also help to mitigate the harsh side effects seen with current therapies that treat all medulloblastomas as equals.

“We hope to find…common pathways that we will be able to block with a reasonable small number of drugs that don’t have horrible side effects and fundamentally change how we treat the tumors,” said Pomeroy. “I would say we are much closer to that today than we were 10 years ago.”

Paaqua Grant, Amanda Mathews, Mathew Raymond, and Carrie House, graduate students from SMHS’s Institute of Biomedical Sciences, also delivered presentations on their research projects.

The day concluded with a panel hosted by the GW Cancer Institute and moderated by its executive director, Steven Patierno, Ph.D., professor of Pharmacology and Physiology at SMHS. Panelists included LaMantia, Dyer, and Pomeroy; Javad Nazarian, Ph.D., assistant professor of Integrative Systems Biology at SMHS; Norman Lee, Ph.D., professor in the Department of Pharmacology and Physiology at SMHS; and Weiqun Peng, Ph.D., associate professor of Physics in the Columbian College of Arts and Sciences.

The panelists discussed the future challenges and possibilities in the realm of neuroscience research.  Nazarian spoke about the promise of using cerebrospinal fluid as a way to detect and target tumors that cannot be isolated. Other panelists addressed the possibility of the existence of cancer stem cells and raised concerns about computational barriers.

“I still feel like there’s a lot hidden in [our] data,” said Dyer. “And I don’t know where it’s going to come from, but I feel there’s going to be a really smart person out there that’s going to figure out a totally out-of-the box way to look at this, and it’s going to revolutionize the way we look at all this data.”

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