Cells are ingenious at keeping everything in balance even when they are threatened by stressors that might otherwise kill them—such as too much heat, excess oxygen, too few nutrients, etc. But scientists are finding that stress-response mechanisms that keep cells alive when they shouldn’t may lead to cancer.
A molecular biologist at the University of Texas Southwestern Medical Center is teasing out the details of how cells respond to stress in order to find new ways to treat cancer. Peter Douglas was recruited in 2015 from the University of California, Berkeley, where he was a postdoctoral fellow, with the help of a First-Time Tenure-Track Award from CPRIT. Douglas was born in San Antonio and spent five years in Dallas as a child while his father was a professor at UT Southwestern.
On the one hand, activating the stress response in cells could help keep them alive—and might be a key to preventing or treating neurodegeneration, for example. On the other hand, cells that are too good at responding to stress might not die when they should.
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Cells are ingenious at keeping everything in balance even when they are threatened by stressors that might otherwise kill them—such as too much heat, excess oxygen, too few nutrients, etc. But scientists are finding that stress-response mechanisms that keep cells alive when they shouldn’t may lead to cancer.
A molecular biologist at the University of Texas Southwestern Medical Center is teasing out the details of how cells respond to stress in order to find new ways to treat cancer. Peter Douglas was recruited in 2015 from the University of California, Berkeley, where he was a postdoctoral fellow, with the help of a First-Time Tenure-Track Award from CPRIT. Douglas was born in San Antonio and spent five years in Dallas as a child while his father was a professor at UT Southwestern.
On the one hand, activating the stress response in cells could help keep them alive—and might be a key to preventing or treating neurodegeneration, for example. On the other hand, cells that are too good at responding to stress might not die when they should.
Douglas was attracted by this paradox, which strikes a fine balance between two different disease states. He thinks an overactive stress response may lie at the heart of so-called cancer stem cells, which evade therapy, remain quiescent, and then emerge years later as a more aggressive cancer.
“Most cancer treatments, be it resection or chemotherapy remove most of the tumor,” he says, “but you might have remnants of it sticking around. We think targeting the stress response would be a good way to prevent any relapse of the disease.”
He envisions a gene-therapy treatment that might alter the genome of just the cancer cells, removing a key component of their stress-response mechanism. “We’re still in the infancy of using gene therapy to treat disease,” he says, “but in theory you could get one infusion and it would change the genome of that cancer. And you would not need to go back.”
He says if the gene-therapy idea doesn’t pan out, there are still ways to use gene-editing technology, “to not necessarily edit your genome, but target and silence the gene.” In this case, the treatment wouldn’t be a lifelong fix, and patients would have to go in from time to time as part of a regular regimen. But if it works, it would keep them cancer-free without side effects.
The key to avoiding side effects is that although the gene is present in all cells, it’s only activated during early embryonic development or cancer, while remaining silent in mature cells.
Douglas is also looking at the links between cellular response to stress and both glioblastoma and recovery from traumatic brain injury—in the one case, involving over-proliferation of brain cells and in the other, brain cell death.
He has received nearly $2 million in follow-on funding, including from the National Institutes of Health, the American Federation of Aging Research, and the Texas Institute of Brain Injury Research.
“I’m appreciative and grateful that CPRIT gave me the opportunity to do this research,” he says, adding that it allowed him to take a multidisciplinary approach and take advantage of “amazing” facilities at UT Southwestern.
Douglas received his undergraduate degree in biochemistry from the University of Colorado and his Ph.D. in cell & developmental biology from the University of North Carolina School of Medicine. He was a postdoctoral fellow at the Salk Institute for Biological Studies in La Jolla, Calif., and moved with his advisor to UC Berkeley in 2012.
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