At a glance, most people wouldn’t expect to find research on epilepsy and breast cancer coming out of the same lab. But when it comes to Avtar Roopra’s lab group, those seemingly disparate topics have led to projects that take advantage of uncommon synergies.
A new arrival at UW-Madison in 2001, Roopra, PhD, associate professor of neuroscience, was interested in making discoveries, not cures.
“My role wasn’t to study epilepsy, it was to study neuroscience - how the brain develops and how cells know what genes to have turned on and to have turned off,” he said. “When the brain is developing and learning new information, what sorts of genes need to be turned on? That was my basic question. But in trying to answer that, we realized that some of the things we were discovering about how genes are controlled during learning and memory, might be really important in how genes go awry in a disease like epilepsy.”
It all starts with basic research - learning how the world works - and it ended up with a potential treatment for a devastating condition.
By about 2004, he realized that he and collaborators had identified key mechanisms that might be important for epilepsy. One key realization was that genes important in epilepsy could be manipulated by the types of food we eat, linking diet and epilepsy. Pursuing the mechanism further down the path of discovery and getting strong results along the way, the findings are being pursued by clinicians in Virginia. There, a drug trial is underway, exploring the sugar-mimicking drug 2DG (or 2-deoxyglucose), meant to control the genes responsible for epilepsy based on cellular metabolism.
That was a happy side effect of basic research, according to Roopra. “It all starts with basic research - learning how the world works - and it ended up with a potential treatment for a devastating condition.”
During Roopra’s successes in uncovering some important mechanisms regarding epilepsy, he lost his sister to a highly aggressive form of breast cancer.
“I thought, ‘you know, we have all these resources in the lab and phenomenal computing power. Perhaps with very little effort we could try to produce a side project as a token gesture towards that.’ We were extremely lucky to have an incredibly talented graduate student in the lab, Matt Wagner. He really jumped on the possibility of taking what we knew in epilepsy and looking at breast cancer.”
Wagner made some startling connections between the two diseases. Most notable, he found the same genes that were overactive in the epileptic brain were actually missing in breast cancer, and the fact that they were missing in these tumors made them highly aggressive. With this in mind, the Roopra lab developed a test that can distinguish highly aggressive breast cancer with a 3- to 4-year survival rate - from breast cancers with a survival rate of 10 to 20 years.
“We’ve been pushing that line of inquiry for a few years now and it’s been very fruitful,” said Roopra. “We’ve come up with a kit that allows clinicians to diagnose a breast tumor and see whether the patient is going to be on this good trajectory or this aggressive trajectory.”
The basic science question for Roopra now is why those tumors are so aggressive. “If we can stall their growth to give these patients some hope of surviving not 3 or 4 years, but 15 or 20, that’s extremely rewarding work.”
Two halves create synergy
As work exploring epilepsy and breast cancer continues, both projects edge forward with a sort of cyclical rhythm. From the outside, it seems as though the researchers studying these unrelated diseases are making leapfrog discoveries - first epilepsy, then cancer, then epilepsy, and so on - somehow revealing novel insights to finely tuned eyes.
“The two halves of the lab have synergized and each group pushes the other forward. It doesn’t get more exciting than this,” said Roopra.