BAR HARBOR, MAINE — The MDI Biological Laboratory has announced that James A. Coffman, Ph.D., has received a two-year grant totaling $166,000 from the National Institutes of Health (NIH) for his research on the regulation of cortisol, a naturally occurring steroid that governs how the body responds to stress.
Coffman, a developmental biologist and an associate professor at the laboratory, studies why organisms exposed to chronic early-life stress are more vulnerable later in life — long after a source of stress has been removed — to inflammatory diseases like arthritis, asthma, cancer, diabetes, heart disease and even mental illness.
He uses the common aquarium fish, the zebrafish, as a model to study the gene regulatory circuitry by which chronic exposure to elevated cortisol affects the development of the neuroendocrine stress response system. The award will fund research on a specific gene, klf9, that the Coffman laboratory has shown to be activated by such exposure.
The zebrafish is an ideal model for such research because it is relatively easy and economical to work with and because it shares its stress response system with humans, along with the relevant regulatory genes and gene regulatory circuitry.
“The MDI Biological Laboratory is extraordinarily pleased to announce this award,” said Hermann Haller, M.D., president. “Dr. Coffman is engaged in basic research aimed at elucidating the pathways governing the stress response. Such research is critical to creating a reservoir of scientific knowledge that could one day lead to novel interventions or therapies to mitigate the adult effects of early-life stress.”
The award was made by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Coffman will use the funds to assess klf9’s role in regulating the stress response by comparing wild zebrafish to genetically modified zebrafish that lack klf9 function. The aim of his research is to determine if klf9 is critical to the regulatory circuity controlling stress signaling and to provide a foundation for future research to further elucidate the regulatory networks governing the stress response.
“Dynamic regulation of the body’s stress response system is critical for healthy physiology,” Coffman said. “We have tantalizing evidence to suggest that klf9 is a key gene for understanding both the development and the regulation of the stress response system. This grant will allow us to figure out what it is doing.”
The body’s stress response system is typically turned off when a source of stress is removed, he explained. But if the system is chronically elevated during early development, it remains chronically active later in life. The inflammation and immune system dysregulation that result when the stress switch is permanently set to an “on” position set the stage for the development of chronic disease in later life.
Coffman’s research also has implications for patients who are prescribed synthetic glucocorticoid drugs. While effective at suppressing inflammation over the short term, these widely prescribed drugs can have adverse health effects over the long term, particularly on metabolism — for example, by promoting the development of obesity and metabolic syndrome.
To understand and ultimately mitigate these effects, it will be necessary to gain an increased understanding of how the underlying gene regulatory networks are organized and how they function to control glucocorticoid signaling dynamics.
The award of the grant (number: R03HD099468) will also allow Coffman to gather the preliminary data on the function of klf9 and create the tools that will be required to apply for long-term NIH funding.
About the MDI Biological Laboratory
We are pioneering new approaches to regenerative medicine focused on developing drugs that slow age-related degenerative diseases and activate our natural ability to heal. Our unique approach has identified potential therapies that could revolutionize the treatment of heart disease, muscular dystrophy and more. Through the Maine Center for Biomedical Innovation, we are preparing students for 21st century careers and equipping entrepreneurs with the knowledge, skills and resources needed to turn discoveries into applications that improve human health and well-being. For more information, please visit mdibl.org.