A University of Massachusetts Amherst environmental health scientist has received a $2.44 million, five-year grant renewal from the National Institutes of Health (NIH) to continue her research into how embryonic exposure to certain common pollutants may put people at risk for diabetes and other metabolic health conditions later in life.
Alicia Timme-Laragy, associate professor in the School of Public Health and Health Sciences, examines the impact on the developing pancreas of early life-stage exposures to two common per and polyfluoroalkylated substances (PFAS) chemicals, found in waterproof and nonstick household products, and the PFAS-containing aqueous film-forming foam (AFFF), used to fight flammable-liquid fires. These so-called "forever chemicals" take decades to break down in the environment and have contaminated drinking water worldwide.
A lot of people are working actively to understand what the long-term health implications are of these compounds. We're trying to contribute to the scope of knowledge on what these compounds do, and I think we have a unique opportunity with our model and experimental protocols."
Alicia Timme-Laragy, associate professor, School of Public Health and Health Sciences, University of Massachusetts Amherst
Timme-Laragy and her research team, including UMass colleague John Clark, a professor of environmental toxicology in Veterinary and Animal Sciences (VASCI), use transgenic zebrafish to study the effects of these toxic chemicals on embryonic development.
"We are able to study in real time the effects on a very small subset of cells in live, transparent zebrafish embryos," she says. "It's a unique opportunity."
The researchers will build on one of their key previous findings showing that oxidative stress created from the chemical exposures results in malformations of the developing pancreatic islet, which contains beta cells (β-cells) responsible for synthesizing, storing and releasing insulin.
"We want to better understand these mechanisms and the functional implications of these malformations," says Timme-Laragy, who uses state-of-the-art imaging techniques including confocal microscopy at the Institute of Applied Life Sciences' Light Microscopy Facility.
Pancreatic malformations, which occur in an estimated 10% of the population, are associated with type 1 and type 2 diabetes, as well as obesity and pancreatitis. In zebrafish exposed to PFAS chemicals, preliminary data have shown elevated levels of fructosamine, a clinical biomarker of diabetes in humans.
"That certainly suggests to us that there are long-term implications for development of diabetes later on," Timme-Laragy says. "We want to understand the mechanisms involved within the beta cells and track individual fish that have malformed islets and see what are the effects on glucose homeostasis and the implications for overall growth and metabolism."
Ultimately, the researchers hope to be able to predict the effects of other exposures once they understand the mechanisms occurring in the cells. They also hope to add to the evidence base on the health effects of PFAS chemicals.
The grant summary concludes, "This work will have a sustained and powerful impact on the fields of developmental toxicology, redox biology and the developmental origins of health and disease, and provides critical advances towards developing science-based PFAS guidelines, targets for clinical interventions and public health policies."
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