CHAPEL HILL — Researchers from the University of North Carolina at Chapel Hill School of Medicine have received over $1.6 million in research awards from the Department of Defense to fund two separate studies, one on post-traumatic stress syndrome and the other on breast cancer stem cells.
The first award, given to Thomas Kash, PhD, funds a four-year study to identify some of the factors explaining how soldiers can respond so differently to similar traumatic events. Large numbers of soldiers return from combat missions in Iraq and Afghanistan exhibiting symptoms of post-traumatic stress syndrome (PTSD); however, many come back relatively unscathed. Despite enormous research efforts on the subject, little is known about the genetic and neurobiological factors that underlie stress susceptibility and resilience.
Kash, an assistant professor of pharmacology, has discovered that two distinct strains of mice display strikingly different responses to stressful situations (in this case, being restrained within their cages for certain periods of time). One strain dealt with the stress by becoming anxious and passive; the other by becoming more active.
Kash and his colleagues found that the different coping responses were associated with marked differences in the patterns by which a number of genes were turned on or off in the amygdala -- the emotional center of the brain. Among these genes were members of the glutamate neurotransmitter system, which plays an important role in the excitability or adaptability of the brain. The researchers used electrophysical recordings of neurons in the mice to show that these differences translated to a brain that was either susceptible or protected from the effects of stress.
In collaboration with Andrew Holmes, PhD, section chief and principal investigator at the National Institute on Alcohol Abuse and Alcoholism, Kash will use the $1,243,435 DoD award to expand upon this research by looking at the contribution of two major components of the glutamate system, namely the NMDA receptor and the kainate receptor.
They plan to determine whether altering these components in mouse models could change the way the animals cope. Their findings could one day lead to new screening methods for soldiers at risk of developing PTSD, as well as novel drug treatments to promote positive coping responses to stress.
The second award, given to Pilar Blancafort, PhD, also an assistant professor of pharmacology, funds a two-year study to develop a new treatment to kill the stem cells that give rise to basal breast cancer. This specific subtype of breast cancer is very aggressive and very difficult to treat. Recent studies have indicated that these types of tumors are colonized with what are known as cancer stem cells, effectively “corrupt” versions of the normal cells that give rise to breast tissue.
In collaboration with Brian Strahl, PhD, associate professor of biochemistry and biophysics at UNC and Lineberger Comprehensive Cancer Center member, Blancafort will use the $407,000 DoD award to develop both new therapies to annihilate cancer stem cells and novel tools to render cancer stem cells more vulnerable to chemotherapy and radiation.
The researchers plan to create smart molecules called Designed Epigenetic Remodeling Factors which will specifically recognize and add “epigenetic stop signs” to the damaged genes that are the hallmark of cancer stem cells. These stop signs should cause the cellular machinery to stop reading the genetic messages that control cell division in cancer stem cells, ultimately suppressing their growth.
Blancafort and Strahl will first perform proof of principle experiments in animal models with basal cancer tumors. They will then devise artificial particles or nanoparticles to encapsulate and specifically deliver their designer cancer killers into the tumors. Their findings could lead to a novel clinical approach to thwart basal breast cancer, a devastating illness for which no efficient treatments are currently available.
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