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NIEHS Leads Trans-NIH Initiatives

By Eddy Ball
October 2007

Gwen Collman, Ph.D.
Collman expects the expanded data collection that will emerge from the GEI exposure biology component to increase several fold the power of large epidemiological studies. Miniature, light-weight environmental sensors will provide a level of accurate, real-time data on exposures that surveys alone are incapable of supplying. (Photo courtesy of Steve McCaw)

This graphic illustrates the area of interaction of gene and environmental exposures involved in the development of disease. (Graphic courtesy of Gwen Collman)
This graphic illustrates the area of interaction of genetic factors and exposures involved in the development of disease. (Graphic courtesy of Gwen Collman)

The sensor data and biomarkers that the Exposure Biology component develops will help researchers identify which genetic factors make people more susceptible to disease. (Graphic courtesy of Gwen Collman)
The sensor data and biomarkers that the Exposure Biology component develops will help researchers identify which genetic factors make people more susceptible to disease. (Graphic courtesy of Gwen Collman)

The schematic in Wilson's presentation was similar, but the focus of the Epigenomics Initiative is on the potentially reversible changes in gene expression patterns triggered by environmental exposures. (Graphic courtesy of Sam Wilson)
The schematic in Wilson's presentation was similar, but the focus of the Epigenomics Initiative is on the potentially reversible changes in gene expression patterns triggered by environmental exposures. (Graphic courtesy of Sam Wilson)

The translational potential of the Epigenomics Initiative is significant. Both projects promise to lead to development of new strategies for the prevention and treatment of broad spectrum of conditions, ranging from addiction and inflammation to birth defects, chronic diseases and cancers. (Graphic courtesy of Sam Wilson)
The translational potential of the Epigenomics Initiative is significant. Both projects promise to lead to development of new strategies for the prevention and treatment of a broad spectrum of conditions, ranging from addiction and inflammation to birth defects, chronic diseases and cancers. (Graphic courtesy of Sam Wilson)

During its September 17-18 meeting, the NIEHS National Advisory Environmental Health Sciences Council heard updates on NIEHS involvement in two major trans-NIH initiatives investigating the interplay of genetic and environmental factors in the development of human diseases.

Council first heard a presentation on the Genes, Environment and Health Initiative (GEI) (https://www.nih.gov/news/pr/sep2007/nhgri-04.htm) Exit NIEHS by Gwen Collman, Ph.D. chief of the Susceptibility and Population Health Branch in the Division of Extramural Research and Training (DERT). Shortly afterwards, Acting Director Sam Wilson, M.D., stood in for Office of Director (OD) Special Assistant Brenda Weiss, Ph.D., who is the working group leader, and presented a status report on the Roadmap (RM) 1.5 Epigenomics Initiative.

According to Collman, the GEI aims to accelerate understanding of genetic and environmental contributions to health and disease through a two-pronged approach combining genotyping and the development of next-generation exposure-measurement technologies. The genome-wide association study component will be led by the National Human Genome Research Institute (NHGRI). The Exposure Biology Program, which makes up the other component of GEI, is being coordinated primarily by the NIEHS in partnership with three other institutes and centers (ICs).

The genetic component of GEI uses a strategy which relies on the newfound ability to swiftly identify genetic differences throughout the genome between people with an illness and those who are healthy. This research will lead to an understanding of the underlying genetic contribution to the disease through studies of 15 complex diseases or pathological traits.

The exposure component of the initiative will support interdisciplinary teams of basic scientists, bioengineers, physician-scientists and others working toward three goals:

  • Developing environmental sensors for measuring exposures to toxins, dietary intake, physical activity, psychosocial stress and addictive substances
  • Identifying biomarkers in the human body that indicate activation of disease mechanisms such as oxidative stress, inflammation and DNA damage
  • Integrating sensor and biomarker technologies

GEI research will span four fiscal years, FY2007-FY2010, with projected funding of $98.6 million for the genetic component and $88M for the exposure biology component. A distinctive feature of the grants under this initiative is a provision allowing Intramural researchers to compete for funding.

Wilson is serving as a co-chair of the Epigenomics Initiative along with Nora D. Volkow, M.D., director, National Institute on Drug Abuse (NIDA), and James Battey, M.D., director, National Institute on Deafness and Other Communication Disorders. The initiative is investigating the role of environmental exposures in triggering the epigenetic changes responsible for silencing or over-expressing genes implicated in a host of diseases. The program's working group includes 59 scientists representing 16 institutes and the NIH Office of the Director - including 12 NIEHS researchers.

Wilson outlined the four objectives of the Epigenomics Initiative:

  • To establish an international committee on standard practices and platforms, develop new antibody reagents and create a reference epigenome database
  • To develop epigenomic mapping data and infrastructure to facilitate research in human health and disease
  • To evaluate epigenetic mechanisms in aging, development, environmental exposure (physical, chemical, behavioral, social environments) and modifiers of stress
  • To develop new technology for single cell analysis and remote imaging of epigenetic activity in cells, tissue and whole animals

The initiative will orchestrate research activities under five types of Requests for Applications (RFAs). NIEHS is coordinating RFA1, totaling $50M to fund Reference Epigenome Mapping Centers, and RFA2, to support projects on epigenetic alterations related to aging, development, environmental exposure and modifiers of stress through an $88M allocation of RM/IC funds. NIDA will coordinate RFA3, funding data and computational infrastructure for Mapping Centers ($12M), and RFA 4, to develop new technology/tools for epigenetics ($42M).

Coordinated by the National Institute on Diabetes and Diseases of the Kidney, RFA5 involves $15M to fund the discovery of novel, stable epigenetic marks in mammalian cells. The National Center for Biotechnology Information (NCBI) will spend $12M to develop a publicly accessible epigenomic database.

The Epigenomics Initiative funding is expected to total over $219 M spread over FY2008 to FY2015, along with a $3 M "jump start" allotment for FY2007 planning and coordination.

The initiatives constitute some of the most fundamentally transformative research currently underway at NIH. The design of the initiatives offers both of them the potential for achieving translational results with significant clinical applications.

Trans-NIH Team Work

NIEHS staff in these initiatives represent DERT, OD, Office of Management (OM) and the National Toxicology Program (NTP). They are working with their colleagues from NIEHS and other ICs to maximize resources from across NIH in a concerted effort to address human disease.

David Balshaw, Ph.D., DERT Linda Bass, Ph.D., DERT
John Bucher, Ph. D., NTP Gwen Collman, Ph.D., DERT
Christie Drew, Ph.D., DERT  Lerlita Garcia, DERT
Jerry Heindel, Ph.D., DERT  Laurie Johnson, OM
Pat Mastin, Ph.D., DERT Kimberly McAllister,Ph.D., DERT
RoseAnne McGee, DERT Srikanth Nadadur, Ph.D., DERT
Terry Nesbitt, Ph.D., DERT David Schwartz, M.D., OD
Dan Shaughnessy, Ph.D., DERT   Anne Thompson OD
Sally Tinkle, Ph.D., OD Fred Tyson, Ph.D. DERT
Molly Vallant, Ph.D., NTP Brenda Weis, Ph.D., OD
Sam Wilson, M.D., OD Leroy Worth, Ph.D., DERT

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