The National Institute of Health Sciences (NIEHS)
Center of Excellence in Environmental Health
The theme of our NIEHS Center is to understand the environmental causes of disease by investigating which pollutants, genes, epigenetic programs, and cell signaling pathways influence the processes of disease development. Our Center focuses on several important research areas outlined in Table 1 below, including early detection and prevention, health effects of metals and particulate matter, and susceptibility to environmental disease. Our Center strives to build upon our mounting strength in epigenetics to focus further on this aspect of our theme. We are currently actively recruiting new faculty members to work on epigenetics and toxicology.
Goals and Directions
The broad goals of the Center are the identification, evaluation, prevention, and control of the adverse impacts of environmental factors on human health, with strong focuses in the areas of ambient air pollution effects, environmental and occupational exposures to heavy metals, and the roles of dietary factors in the causation and prevention of human cancer and disease. Further, the Center reaches out to the community (local and regional) providing assistance, information, and education on environmental issues, and training graduate and medical students for productive careers in research, teaching, and other professional services. The Center also guides its members into new research areas of interest to the NIEHS involving modern technology or research areas that are timely and may have significant environmental impact (e.g., our rapid response to the WTC disaster; currently, we have recruited cohorts from those exposed to WTC dust for long term disease follow up). The Center supports investigator-initiated pilot projects, as well as encourages initiatives via RFPs in new areas that the Center and NIEHS deem important for future studies of the impacts of the environment on human health and disease.
The NYU NIEHS Center is a highly interdisciplinary research organization that has successfully applied a wide range of research talents and perspectives to the studies of environmental health issues. Because of its scope, the Center has created opportunities for collaborative and multidisciplinary research across diverse program areas, such as epidemiology with molecular biology, and human exposure assessment with basic toxicology, as well as integrating molecular biology into all aspects of toxicology. In 2009, following the guidance of our External Advisory Committee, and with the approval of our Internal Advisory Committee, our Center's previous research programs have been reorganized into specifically defined focused working groups, as illustrated in Table 1 below.
Primary members of the Center must have peer-reviewed funded grants either ongoing or funded within the last 2 years, while associate members include part-time or joint faculty that enrich our Center by their interactions with primary members. The Focus Groups have been meeting regularly. A number of collaborations have resulted from these interactions within the Focus Groups. For example, a new research initiative focuses on air pollution and epigenetic effects in children (Drs. Gordon and Reibman). Among the Center members, there is extensive interest in nickel as a major toxic component of particulate matter (PM) air pollution, as well as extensive research on the epigenetic mechanisms of nickel carcinogenesis. The Metals Focus Group has led to a number of collaborations including one between Drs. Costa and L.C. Chen on epigenetic changes in the lungs of mice exposed chronically (3 to 6 months) to nickel nanoparticles as well as a collaboration with Dr. Gordon on epigenetic changes in mice exposed to chromate. In addition, through the IHSFC, Dr. Qu has collected lymphocytes from control workers and nickel refinery workers, in China, who have had a very high exposure to nickel. These lymphocytes are being processed using cutting edge ChIP-Seq technology to map histone H3K4 trimethylation and H3K9 dimethylation throughout the genome. These highly novel results will be correlated with gene expression changes in lymphocytes which should lead to delineation of not only baseline inter-individual levels of gene expression, but also to elucidation of changes in gene expression mediated by epigenetics effects following environmental nickel exposures. Thus, our previous basic science studies on nickel-induced changes in histone methylation in cultured cells is being translated into the public health arena using humans exposed to nickel either environmentally or occupationally. From a clinical standpoint, it will be important to understand the nature of metal-induced epigenetic effects so that early changes during carcinogenesis may be elucidated, leading not only to early detection and strategies for prevention, but also to biomarker development, as well.
As illustrated in Table 1, the Center has strengths in Early Detection and Prevention, Heavy Metal Toxicology and Carcinogenesis, Particulate Matter, and Susceptibility to Environmental Disease. Ongoing research encompassing Experimental Studies, Biomarker Development as well as Epidemiological Studies is evident across each of these Focus Groups. Thus, two leaders have been chosen for each Focus Group. One leader conducts primarily human studies (either Epidemiology or Biomarker Development), while the other leader has expertise in experimental studies or bench research. This dual leadership ensures that translational research will be actively coordinated with basic research within each Focus Group area.
The Center has recently engendered the establishment of a partnership with Dr. Thomas Begley at the GeNYsis Center of the State University of NY at Albany to utilize his yeast knockout strains of non-essential genes to assess fundamental interactions between genes and metal exposures. This collaboration involved a number of Center members including Drs. Dai, Gordon, Klein, and Costa and was funded in part by the Director’s fund and by our Molecular Cell and Analytical Services Facility Core. We investigated the sensitivity and resistance of each knockout strain to chromate, arsenite, nickel, zinc, and ozone. Deletion of a number of non-essential genes led to resistance or sensitivity to the various metals, and the use of this unbiased whole genomic approach has provided knowledge on how metals could be toxic to an organism through interactions with single genes. This collaboration has already led to several publications (Genomics 2009;94:294-307, BMC Geonomics 2009;10: 5241) and has seeded further studies on the nuances of gene-environment interactions related to exposures to metals. The interactions of metals with several genes identified in the yeast screens are also being investigated in human cells. If changes in any of these genes can be validated as biomarkers of exposure or effect, further translation research will be needed to evaluate whether single nucleotide polymorphisms (SNPs) in such genes can modify the risk of human disease resulting from exposure to metals.
The Focus Groups have also initiated the invitation of guest speakers to the Center to invigorate interactions. For example, the Particulate Matter and Metals Focus Groups invited Dr. Michelle Bell of Yale University to speak on her latest research in a presentation entitled “The Health Impacts of Particulate Matter Constituents” on September 18, 2009.
The primary mission of our broad-based Center is to nurture and focus a diversity of research topics on the recognition, evaluation, prevention, and control of the adverse impact of environmental factors on human health. This mission has been achieved in the past through the interactions between the research cores that stimulated studies addressing the Center’s goals, and is supported by centralized core facilities that provide individuals and teams of Center members with information, expertise, and technical assistance in specific operations (e.g., analytical chemistry, inhalation exposure, animal care and specialized animal exposure, gene expression and genotyping analyses, computational biology, biostatistics), as well as state-of-the-art equipment (e.g., high throughput RT-PCR, confocal microscopy, FRET, atomic force microscopy, microarrays, ChIP-on-chip, ChIP-Seq, DNA sequencer, and proteomics technology). We will continue the tradition of the previous research cores through the newly reorganized Focus Groups shown in Table 1.
The Center’s continued coordination and application of broad-based scientific talents and research techniques will: 1) facilitate research that pointedly relates environmental factors to human disease; 2) identify mechanisms responsible for the adverse health effects produced by environmental agents; 3) study the relationship between genes and environmental factors that activate or deactivate genes contributing to differences in population and inter-individual variation in susceptibility to the development and progression of human diseases; 4) focus on epigenetic parameters affected by environmental agents and how changes in these parameters lead to diseases, such as cancer and asthma, and serve as a basis for adult disease following early life insult; and 5) develop methods for the detection, prevention and control of environmental exposures that cause or exacerbate human diseases.