NIEHS initiatives to advance research on DNA and RNA modifications associated with environmental damage were the focus of a recent meeting of the National Environmental Health Science Advisory Committee. NIEHS Director Rick Woychik, Ph.D., along with institute leaders, scientists and funders, reported the latest research progress to the advisory board on February 12-13.
They shared progress guiding the scientific community’s research on the exposome, developing new models for environmental justice, and appointing new leaders, including the NIH director and scientific director of the Division of Translational Toxicology.
The committee is a congressionally mandated agency that meets three times a year to advise Woychik on the direction of research, training, and professional development supported by NIEHS. The committee also conducts a secondary review of research grant applications.
![Dr. Trevor Archer](https://factor.niehs.nih.gov/sites/niehs-factor/files/2024/02/community-impact/council-body1.jpg)
Environment changes DNA, RNA
NIEHS Program Director Fred Tyson, Ph.D., organized a mini-symposium highlighting the work of researchers who are exploring the impact of the environment on epigenetic changes in DNA (epigenomics) and RNA (epitranscriptomics). For nearly three decades, NIEHS has actively supported research at the intersection of the environment and the epigenome.
“Recognizing the potential impact of environmental toxicants on RNA modifications and the mechanistic links this may have to many health outcomes, NIEHS began developing a portfolio in 2017 to combine exposure with epitranscriptomic studies,” Tyson explains. “
Today, seven years later, NIEHS is supporting more than 35 active grants focused on exposure and epitranscriptomics.
![Dr. Fred Tyson](https://factor.niehs.nih.gov/sites/niehs-factor/files/2024/02/community-impact/council-body2.jpg)
The following NIH-supported scientists presented their exciting research results at the Board of Governors meeting.
- Dr. Yingsheng Wang shared his use of multi-omics approaches to study the role of CAG repeat RNA in neurodegenerative diseases, including Huntington’s disease and diseases marked by accumulation of the protein TDP-43. Using a variety of laboratory models, including cell, worm, fly and mouse models, Wang and his UC Riverside team showed that the longer the repetition, the higher the enzyme activity, leading to cell destruction.
- Dr. Yvonne Fondufe-Mittendorf of the Van Andel Institute discusses her team’s efforts and models to understand how arsenic causes cancer. Fondufe-Mittendorf showed that arsenic directly alters the primary and tertiary (3D) structure of chromatin (a mixture of DNA and proteins), leading to altered gene expression patterns that promote tumorigenesis. Arsenic also increases the expression of circular RNAs that disrupt higher-order chromatin structure, which can also lead to cancer.
- Former ONES awardee Dr. Justin Colacino of the University of Michigan describes his use of single-cell approaches. Objective: To delve into the spatial distribution of markers at the tissue level to study differences in environmental exposure and cellular plasticity, or the transformation of a cell’s identity from luminal to basal.
- Dr. Victor Corces of Emory University discusses how environmental influences can lead to inherited epigenetic defects that are passed down from generation to generation. He shared research showing that epigenomic changes can be passed down from generation to generation. He found that bisphenol A (BPA) causes transcriptional changes that allow BPA-induced obesity to be inherited across generations in mice.
- Tom Begley, Ph.D., of the RNA Institute and a 2006 ONES grantee, explains how transfer RNA (tRNA) is regulated by stress and environmental exposure. He shared evidence that the mouse epitranscriptome is reprogrammed in response to environmental tobacco smoke. “We need to connect the exposome to the epigenome and use it as a filter to get the epitranscriptome,” he said.
- “Differential RNA modifications associated with disease can change dramatically with single amino acid mutations,” said Yunsun Nam, Ph.D., a biochemist and structural biologist at the University of Texas Southwestern Medical Center. Nam discusses her efforts to understand atoms Efforts are made to understand what is happening at the structural level. Her goal is to provide new insights into how RNA and protein machinery work together, with the goal of revealing signaling pathways that can be regulated or repaired.
- Dr. Ting Wang, a genomic scientist at Washington University in St. Louis, explained that the environment affects the genome and epigenome, and cancer evolves from genetic and epigenetic causes. He shared that transposable elements can be demethylated—an epigenetic change—which can lead to high expression of oncogenes even in the absence of genetic mutations. “Epigenetics is reversible, the epigenome is targetable, so this provides us with an opportunity to trick cancer cells into producing neoantigens and target transposable elements for cancer therapy,” Wang said.
![Zhao Shanshan, Ph.D.](https://factor.niehs.nih.gov/sites/niehs-factor/files/2024/02/community-impact/council-body3.jpg)
Director’s report to the Board of Directors
Dr. Woychik introduced board members to the biggest news since the meeting last September: Monica Bertagnolli, MD, has been confirmed as the new NIH director.
Woychik said Bertagnolli’s vision focuses on engaging all communities and leveraging the knowledge and discoveries generated in NIH laboratories and clinics so that all people can live long, healthy lives. She also seeks to strengthen collaboration among the 27 institutes and centers to harness the power of artificial intelligence and machine learning to advance research and increase public confidence in science.
“In my conversations with her, it was clear that she was excited to learn more about how greater awareness of the role of the environment and the exposome could be integrated into the fabric of NIH’s disease etiology research efforts,” Woychik said.
Wojcik also shared updates on emerging scientific priority areas, including the exposome (see sidebar), the new on-campus virtual research center on climate change and health, and environmental justice.
Notably, Woychik announced that U.S. Army Environmental Command would Excavation of up to 300 tonnes of contaminated soil at Western Power’s Tarheel Army missile factory has begun. This is the first time in decades that a partnership with environmental justice groups has made progress on cleaning up the site.
![Last November, NIEHS convened and coordinated a forum that brought together local, state and federal officials to work together to clean up a contaminated site in Burlington, North Carolina. (Photo by Steve McCaw/NIEHS)](https://factor.niehs.nih.gov/sites/niehs-factor/files/2024/02/community-impact/councilj-body4.jpg)
“We hope to expand this model of NIEHS serving as convener and coordinator to other environmental justice communities across the United States,” Woychik said.
(Caroline Stetler is editor-in-chief of Environmental Factors, a magazine published monthly by the NIEHS Office of Communications and Public Liaison.)