Andrea C. Gore, Ph.D., professor of pharmacology and toxicology and Vacek Chair in Pharmacology, recently earned an R35 RIVER grant award from the National Institute of Environmental Health Sciences (NIEHS) for her lab’s research on endocrine-disrupting chemicals (EDCs) and their effect on the brain. The NIEHS, which is one of the centers in the National Institutes of Health (NIH), awarded a total of $6,823,672 for eight years.
The project, titled "Environmental Epigenetics of EDCs: From Germline to Brain," seeks to understand how exposures of rats to EDCs, at levels comparable to human exposures, affect brain development and lead to multi-generational neurological and endocrine disorders. This work is predicated on evidence that environmental EDC exposures, especially during early life, are strongly linked to adverse health outcomes. How EDCs impair future generations will also be addressed by studies on their molecular epigenetic actions in the germline (precursors to sperm and eggs), which can pass heritable information to children and grandchildren.
The project will provide novel information on both direct and inherited mechanisms of EDCs on health and disease. Because effects of EDCs in rats mirror those in humans, the results will lead to a better understanding of human exposures, how EDCs act and how to mitigate their effects.
Through the NIEHS Revolutionizing Innovative, Visionary Environmental health Research (RIVER) R35 program, Dr. Gore and her team plan to address the three overarching areas of inquiry:
- What are the epigenetic mechanisms by which environmental EDCs organize brain development at the cellular level and lead to functional neurobiological deficits in exposed individuals?
- Which epigenetic mechanism(s) is responsible for programming of the germline to enable transmission across generations?
- How does epigenetic programming in the germline manifest as cell-specific phenotypes in somatic cells (e.g. brain)?
By addressing these aims, these studies will open new avenues of inquiry previously lacking in EDC research. “Most EDC research is limited to a single tissue type or a single mechanism with a limited number of targets. This is particularly complicated in the brain because of its heterogeneity. The field is also limited by a surprisingly small number of studies that compare sex differences, yet EDCs have profoundly different effects on the developing male and female brain, body, and germline, which are subject to sex-specific epigenetic programming and phenotypes.”
The NIEHS Revolutionizing Innovative, Visionary Environmental health Research (RIVER) program is intended to provide support for outstanding investigators in the Environmental Health Sciences, giving them intellectual and administrative freedom, as well as sustained support to pursue their research in novel directions in order to achieve greater impacts. The program seeks to identify individuals with a potential for continued innovative and impactful research and combine their existing investigator-initiated research into a single award to support the majority of their independent environmental health sciences research program. Dr. Gore was one of only four investigators awarded an NIEHS RIVER grant in 2023.