Fiscal Year 2013 Budget
Authorizing Legislation: Section 301 and title IV of the Public Health Service Act, as amended.
Budget Authority:
| FY 2011 Actual |
FY 2012 Enacted |
FY 2013 President's Budget |
FY 2013 +/- FY 2012 |
|
|---|---|---|---|---|
| BA | $682,582,000 | $684,755,000 | $684,030,000 | -$725,000 |
| FTEs | 676 | 676 | 669 | -7 |
Program funds are allocated as follows: Competitive Grants/Cooperative Agreements; Contracts; Direct Federal/Intramural and Other.
Director's Overview
The National Institute of Environmental Health Sciences (NIEHS) exists to support the very best science seeking to discover how the environment affects people’s health, and to communicate the results of that science to individuals, communities, and policymakers with the goal of preventing disease and promoting healthier lives. Within the NIH, NIEHS occupies a special place: not devoted to a specific organ or disease, but uniquely empowered to follow the lines of scientific evidence of environmental influences wherever they might lead. The breadth of this mission has served NIEHS and the nation well; for example, our comprehensive understanding of the basic mechanisms of environmental contaminants like dioxin and lead allows us insight into a myriad of health outcomes such as cancer or developmental problems. Similarly, studying air pollution or diesel exhaust particulates can lead us to an understanding of respiratory outcomes, cognitive deficits, and cardiovascular health. Approximately 83 million Americans suffer some form of cardiovascular disease,1 with significant associated costs in terms of human suffering, health care costs, and lost productivity (the costs for cardiovascular disease and stroke alone were estimated in 2007 at nearly $286 billion a year).2 This focus, at the nexus of exposure and disease, gives NIEHS research its value as the foundation of good public health decision making in the prevention of environmentally-related diseases and disabilities.
NIEHS has embarked on a 15-month process of Strategic Planning for the next five years. In consultation with our scientists and key outside stakeholders, we have reaffirmed our mission and vision and are developing a set of Strategic Pillars and Goals to guide and optimize our research investments. The vision of the NIEHS is to provide the nation’s leadership for innovative scientific research that result in improved public health through preventing disease and disability caused by the environment.
Theme 1: Investing in Basic Research: Some of the most important issues in basic biomedical research are also at the heart of how the environment influences human biology and health. For example, the science of epigenetics is growing in importance for our understanding of how all genes are regulated. Epigenetics is the study of changes to the packaging of the DNA molecules; these changes in packaging and other DNA modifications influence the expression of genes and thus all the normal and pathogenic processes for which genes are responsible. Research on models of epigenetic processes has been demonstrating a key role for effects of environmental exposures through epigenetic mechanisms.3,4,5,6 NIEHS has led a trans-NIH Common Fund initiative in the area of epigenetics research, and is continuing its own robust investment in this area.
Theme 2: Accelerating Discovery Through Technology: NIEHS stands at the forefront of applying state-of-the-art biomedical science tools to critical questions in environmental health. Proteomics, genomics, and metabolomics are all examples of the comprehensive or “omics” approaches to biology, making new discoveries and understanding of proteins, genes, and metabolism possible. For example, the rapidly developing field of proteomics (study of the “proteome” or entire set of proteins expressed by a cell, tissue or organism) uses new mass spectrometry-based methodologies to identify “protein signatures”—hundreds to thousands of individual proteins expressed in combination that can be identified and measured—that can be used to link specific environmental exposures with certain disease outcomes. One such NIEHS-funded research effort is focusing on understanding how children’s early exposure to pet dander creates a protective effect against later development of asthma by looking at specific proteomic signatures. Another project is using proteomics and genomics technologies, including the breakthrough technology of toxicity assays that can test thousands of chemical samples on tiny microchips, to identify biological markers of exposure to chemicals such as bisphenol A (BPA) and genistein. This NIEHS-funded group is using a microchip assay approach to create a high-throughput system that will allow us to measure DNA damage far more rapidly than before.
Theme 3: Advancing Translational Sciences: NIEHS research priorities are established with the goal of solving real-world problems in environmental health. One of the critical areas in translational environmental health science is predictive toxicology, or how to incorporate our knowledge of key pathways, molecular events, and processes linked to disease or injury into a research and testing framework that will enable us to predict health outcomes and take preventive action to avoid adverse effects. NIEHS/NTP (National Toxicology Program) has partnered with the National Human Genome Research Institute, the Environmental Protection Agency, and the Food and Drug Administration to incorporate or integrate this knowledge into a new testing paradigm that uses quantitative high-throughput screening assays to test a large number of chemicals for their ability to affect important cellular pathways and biological processes. As we build a knowledge base of these results across chemicals and across testing screens, we will be able to create a framework for making better predictions about the toxic properties of the large numbers of chemicals and drugs that have not been adequately tested.
Theme 4: Encouraging New Investigators and New Ideas: NIEHS actively seeks to develop the pipeline of talented new scientists for the field of environmental health research. NIEHS programs are aimed at fostering interest in science and discovery at all levels, from K-12 through college, graduate study, and postdoctoral training. NIEHS pioneered the establishment of transition-to-independence awards that are targeted to the needs of early investigators just emerging from postdoctoral study and attempting to establish their own labs. In order to solve the complex and widely varying nature of environmental health problems, NIEHS supports training programs in multiple disciplines including genetics, cell and molecular biology, toxicology, exposure science, epidemiology, and others.
NIEHS is proud to be at the forefront of the use of state-of-the-art biomedical science to understand exposure-disease relationships and create the knowledge necessary to solve current and future problems in environmental public health.
Budget Policy: The FY 2013 President’s Budget request for NIEHS is $684.030 million, a decrease of $725 thousand, or 0.1 percent from the FY 2012 Enacted level. NIEHS will continue to support new investigators and to maintain the number of competing RPGs. In FY 2013, no inflationary increase will be provided for non-competing grants and they will be reduced one percent below the FY 2012 Enacted level. NIEHS will also reduce the average cost of competing grants one percent below the FY 2012 Enacted level. In addition, NIEHS has targeted a portion of the funds available for competing research project grants to support high priority projects outside of the payline, including awards to new investigators and early stage investigators. The Institute also seeks to maintain a balance between solicitations issued to the extramural community in areas that need stimulation and funding made available to support investigator-initiated projects.
NIH will provide an across-the-board increase in FY 2013 of 2.0 percent for stipends levels under the Ruth L. Kirschstein National Research Service Award training program consistent with recommendations from the National Academy of Sciences. This will build on the 2.0 percent increase in stipend levels for FY 2012. Stipend levels were largely flat for several years, and the requested increase will help to sustain the development of a highly qualified biomedical research workforce.
Intramural Research and Research Management and Support are funded at the same level in FY 2013 as in FY 2012. Funds are included in R&D contracts to support trans-NIH initiatives, such as the Basic Behavioral and Social Sciences Opportunity Network (OppNet).
Program Descriptions and Accomplishments
Clinical and Translational Research: Bench to Bedside to Public Health
This program encourages integration of clinical, population, and community-based research to translate findings into improved public health practice and disease prevention. Genome-wide association studies (GWAS) have been successfully used to identify susceptibility genes for many common diseases. Unfortunately, genes that influence disease through their interactions with other genes or with environmental factors are difficult to detect through GWAS. In August 2011, a group of NIEHS-funded researchers and others published a groundbreaking study using a novel method called Genome-Wide Association and Interaction Study (GWAIS) to identify gene-environment interactions in Parkinson’s Disease (PD).7 These researchers focused on PD as an important disease with known associations to both specific genes and specific environmental influences (having both protective effects and deleterious effects). Using several cohorts, they checked the interaction of over 800,000 gene variants against consumption of caffeinated coffee by the individual subjects. The findings identified a novel PD modifier gene, called GRIN2A. This gene encodes a portion of a neurological receptor, the NMDA-glutamate-receptor known for regulating some types of neurotransmission in the brain and controlling movement and behavior. The gene had not turned up in previous GWAS studies of PD because its effect is small when considered independently of the interaction with coffee. This study is proof of concept that inclusion of environmental factors can help identify genes that are missed in GWAS. GRIN2A may be a useful pharmacogenetic marker for subdividing individuals in clinical trials to determine which medications might work best for which patients.
Budget Policy: The FY 2013 President’s Budget request for this program is $202.131 million, an increase of $9.153 million, or 4.7 percent over the FY 2012 Enacted level. Research will be used to support a variety of clinical and translational research activities, including the increasing translational research capacity through our new translational research consortia.
Program Portrait: Environment and Autism
| FY 2012 Level: | $6.3 million |
| FY 2013 Level: | $6.3 million |
| Difference: | $0.0 million |
The number of children diagnosed with autism spectrum disorder (ASD) has increased in the U.S. in the past several years. NIEHS conducts and funds multiple projects investigating environmental links to autism, and actively participates in the Interagency Autism Coordinating Committee, a group of Federal agencies and public members (parents and people living with autism) that works to coordinate scientific research on this disorder. NIEHS’s two largest efforts on autism are the Childhood Autism Risks from Genes and the Environment (CHARGE) study, and the Early Autism Risk Longitudinal Investigation (EARLI) study. In the CHARGE study, led by the Children’s Center at the University of California at Davis, researchers are looking at more than 1,600 children in three groups: children with autism, children with developmental delay who do not have autism, and children from the general population. All of the children are evaluated for a broad array of environmental exposures and susceptibilities with the goal of better understanding the causes and contributing factors for autism or developmental delay. A significant recent finding is that 40 percent of children with autism show evidence of regression, defined alternatively as the loss of language and social skills after developing normally up to that point, or loss only of social skills. This is much higher than previously thought and indicates that requiring loss of language in the definition significantly underestimates the frequency of developmental regression. In the EARLI study, researchers at the Drexel University School of Public Health are enrolling 1,000 mothers who have a child with autism and who are pregnant again. The study, which is part of the trans-NIH Autism Centers of Excellence (ACE) Program, will follow the mothers during their pregnancy and their new babies through age three to identify in real time prenatal, neonatal, and early postnatal environmental exposures that may influence their risk of developing autism. NIEHS also partnered with UC-Davis and Autism Speaks on a workshop that brought together parents, educators, community clinicians, scientists, media, and policy makers to explore issues surrounding the ethics of communicating scientific findings on autism risk.
1. https://www.cdc.gov/ncbddd/autism/data.html "State of Research on Potential Environmental Health Factors with Autism and Related Neurodevelopment Disorders" Senate Environment and Public Works Subcommittee on Children’s Health August 3, 2010
Toxicity Testing and Evaluation
This program comprises the NIEHS extramural research investment of the National Toxicology Program, whose mission is to evaluate environmental agents of public health concern, and generate information to be used by health regulatory agencies to make informed decisions affecting public health. NTP also works to develop new and improved test methods, including alternatives to animal testing and high-throughput methods to test substances faster, in order to disseminate useful public health information more rapidly. NTP research also helps to develop new and improved models of toxicity that can help to predict cancer and other adverse health outcomes that may result from fetal or early life exposures. For example, a mouse transplacental model has been developed in which maternal exposure to inorganic arsenic either acts as a complete carcinogen or enhances carcinogenic response to other agents to which the offspring are subsequently exposed to produce tumors during adulthood.8 This model suggests that arsenic acts to enhance the number and survival of cancer stem cells. Because inorganic arsenic causes cancer in multiple human tissues including the bladder, skin, and lung, as well as the liver, kidney, and prostate, this model should provide useful information on stem cell-based cancers caused by developmental exposure to other toxicants as well.
Budget Policy: The FY 2013 President’s Budget request for this program is $88.943 million, a decrease of $0.179 million, or 0.2 percent below the FY 2012 Enacted level. Resources in this program are supporting novel toxicology methods to improve our ability to assess risk and to understand toxic effects at the cellular and molecular level.
Basic Mechanisms in Human Biology
Environmental toxicants can interrupt normal biological processes and initiate events leading to disease. This program uses environmental toxicants as laboratory probes for studying the complex molecular pathways that lead to chronic disease, identifies methods to diagnose these diseases before they are clinically evident, and develops early interventions to prevent progression to end-stage disease.
NIEHS-supported researchers reported in the November 2011 issue of Nature Nanotechnology9 the mechanics of how cells are doomed to fail when attempting to engulf carbon nanotubes specifically due to the shape of the nanomaterial. Carbon nanotubes have a variety of uses in materials science because of their high strength to weight characteristics and in medicine as targeted drug delivery devices. Carbon nanotubes that are closed on one end appear like spheres to the cells. In the process described in the paper, cells begin to engulf the rounded end and often orient the nanotube so that it is perpendicular to the cell membrane. As the nanotube brushes up against the membrane, special receptors send signals that cause the cell to wrap its membrane around the nanotube. As this occurs, the nanotube is tipped to a 90 degree angle, effectively reducing the amount of energy needed for the cell to engulf what it inaccurately senses is a small particle. Within minutes, the cell senses it will not be able to completely engulf the nanotube, but once the engulfing process begins, there is no corresponding signal to stop and reverse the process. The cell then mounts an immune response that results in chronic inflammation. As this process is very similar to the reaction of cells to asbestos, it has potentially high applicability to existing environmental health problems. This research also is important for scientists to fully understand how cells and nanomaterials interact so that nanostructures can be designed safely.
Budget Policy: The FY 2013 President’s Budget request for this program is $126.799 million, a decrease of $1.758 million, or 1.4 percent below the FY 2012 Enacted level. In large part, this decrease represents the completion of several earlier initiatives.
Exposure Biology/Exposure Measurement
This program seeks to develop improved methods to detect and measure environmental exposures in humans or other organisms. Identifying hazardous agents in the environment can be a difficult task; many environmental factors that pose significant risks to human health are actually non-toxic in the form to which humans are exposed but are metabolized by the body’s enzymes into highly reactive, toxic compounds. Through a series of publications this past year, an NIEHS-funded researcher and colleagues demonstrated the power of a new technology to detect such compounds and predict their toxicological potential. The technology is based on the ability to embed the human metabolic enzymes in a nanoscale film on an electrochemical sensor in a technology called a microfluidic array. Essentially, non-toxic agents that can be metabolized by the body into toxic forms are applied to the assay film. The technology generates an electrical current when the enzymes metabolize the non-toxic compounds into a toxic form, thereby identifying the conditions under which they are metabolized. 10, 11 This research group has recently shown the ability to detect compounds using this technology by demonstrating its success using pollutants that are known to metabolize into toxic forms. This microfluidic array is the first demonstration of the use of an electrochemical sensor system to assess the metabolism of potentially harmful environmental compounds.
Budget Policy: The FY 2013 President’s Budget request for this program is $23.110 million, a decrease of $7.602 million, or 24.75 percent below the FY 2012 Enacted level. A large portion of this decrease is due to the ending of the previous RFA known as DISCOVER. In addition, exposure detection technology work is proceeding to the point where plans for FY2013 and beyond call for reducing investment in new tools and focusing resources on validation and field testing of the new exposure assessment tools and biomarkers that have been identified through previous work.
Program Portrait: Next Phase of the Exposure Biology Program/Genes, Environment and Health Initiative
| FY 2012 Level: | $7.1 million |
| FY 2013 Level: | $6.5 million |
| Difference: | -$0.6 million |
The Genes, Environment and Health Initiative (GEI) was started in 2007 to create a technological foundation for investigating the interaction between environmental and genetic underpinnings of human disease. The Initiative consisted of two major components: identifying genetic susceptibility factors for diseases with high public health impact and developing new technologies for accurate measurement of environmental exposures and lifestyle factors. The Exposure Biology Program (EBP) was established to develop a set of tools for assessing individual exposure to environmental stressors, including airborne toxic chemicals, psychosocial stress, addictive substances, and diet and physical activity, as well as measures of the biological response to those stressors. A number of exciting technologies have been created or adapted under this program, including dietary assessment methods using cell phone and digital imaging; miniaturized personal monitors for black carbon and other air pollutants; early disease biomarkers for PCB exposure; and an integrated measurement system to assess physical activity. The evolution of this program builds on the success of the initial phase in creating these prototype technologies. In FY 2013, the EBP will focus on:
- Validation of tools and candidate biomarkers for exposure biology, including assessment of the scientific value of the tools in an epidemiological setting.
- Development of wearable tools for characterization of the personal environment that are minimally intrusive and encourage full use so that researchers can assess exposure to multiple factors in the wearer’s environment simultaneously.
- Field deployable tools for multi-analyte biomonitoring of environmental exposures, to develop a new set of tools based on in vitro diagnostic or lab-on-a-chip technologies to assay the levels of environmental factors in readily accessible biological samples.
NIEHS will also continue work under this program to promote new methodologies for studies of gene-environment interactions by integrating environmental measures into analyses of human population studies.
Pathways for Future Environmental Health Scientists
This program's goal is to attract the brightest students and scientists into the environmental health sciences field to ensure a cadre of professionals to conduct the interdisciplinary research necessary to solve critical environmental health problems. This program includes efforts at the high school and undergraduate levels (opportunities for laboratory-based training), the graduate level (institutional and individual training grants), and the faculty level (grants for young investigators and short term sabbatical awards). The Mentored Clinical Scientist Development Award program supports the development of outstanding clinician research scientists who demonstrate the potential to develop into independent investigators. One scientist currently supported under this program is investigating immune responses and human airway disease from exposure to organic dust in swine confinement facilities. This researcher has developed an in vivo mouse model of intranasal dust exposure that results in exaggerated airway inflammation and tissue injury.12 This model, which appears to mimic the well-recognized adaptation response described in humans, will allow for qualitative and quantitative measures of dust-induced inflammation useful for studying mechanistic regulation of environmentally triggered lung disease. This research has demonstrated novel aspects related to organic dust-induced inflammation that are relevant to human airway disease. In particular, in contrast to the current dogma which focuses on endotoxin-driven mechanisms, this study strongly suggests that Gram-positive bacteria cell wall products may be the principal drivers of inflammation. This result could have important consequences for environmental sampling strategies and targets for potential prevention and therapeutic interventions in humans.
Budget Policy: The FY 2013 President’s Budget request for this program is $34.503 million, a decrease of $0.339 million, or 0.97 percent below the FY 2012 Enacted level. Resources will be used to continue ongoing training programs at undergraduate, doctoral, postdoctoral, and early- and mid-career levels.
Intramural Research
The mission of the NIEHS intramural research program is to investigate the role of environmental agents in human disease and dysfunction and define the important biological and chemical processes that these agents affect. NIEHS intramural research studies are often longitudinal and not immediately translatable into diagnostic or therapeutic tools, and comprise unique components, such as NIEHS contribution to the NTP, epidemiological studies of environmentally associated diseases and exposures (including the new study of individuals exposed by the Gulf oil spill), and intervention and prevention studies in humans to reduce the effects of exposures to hazardous environments. The NIEHS Clinical Research Unit provides opportunities for clinical and basic scientists in the Intramural Program to collaborate and learn how environmental exposures influence human health and disease. Among many important lines of research, NIEHS intramural scientists are studying the mechanisms that control the ability of environmental substances to cross from the blood into the brain. The body has a remarkable blockade system to prevent access to the brain, termed the “blood-brain barrier.” Cellular proteins called “transporters” are required to move substances in and out of the brain. A recent finding identified a common cellular receptor protein as a mediator of the action of these transporters. This protein, termed the Aryl Hydrocarbon Receptor or AhR, senses the presence of many deleterious toxic chemicals, including dioxin. NIEHS intramural scientists demonstrated that when dioxin was bound to AhR in rat brain capillaries, there was an associated increase in activity and expression of the P-glycoprotein transporter molecules, leading to changes to the accessibility of the drugs and environmental agents to the brain that are affected by this transporter.13 These findings introduce a completely new framework for understanding how environmental exposures affect health – by altering the vulnerability of the brain itself.
Budget Policy: The FY 2013 President’s Budget request for this program is $184.771 million, the same as the FY 2012 Enacted level. Resources will be continue to support the demand for bioinformatics in high-throughput screening, toxicogenomics, epigenomics, systems biology and database integration.
Program Portrait: Understanding Environmental Influences on Chemical “Marks” in DNA that Modify Gene Expression: the "Methylome Project"
| FY 2012 Level: | $0.9 million |
| FY 2013 Level: | $0.3 million |
| Difference: | -$0.6 million |
Recent advances in DNA molecular biology have identified many enzymes that can chemically modify the four DNA bases. Some of these modifications affect the activity of the genes in the cell in which they are found. Most prominent is methylation -- the attachment of a simple methyl group [CH3] to certain cytosines. Some methylation patterns are associated with production of liver tumors in laboratory mice. Because strains of mice differ in the likelihood that they will develop liver tumors, investigators hypothesize that the patterns of methylated cytosines in the livers of each strain also may be different. The NIEHS “Mouse Methylome Project” has been developed to answer these questions.
The primary goal will be to use high throughput [“NextGen”] DNA sequencing machines to create a high resolution map of the mouse liver methylome from three different mouse stains. These strains show dramatically different incidences of spontaneous liver tumors. A major premise of this project is that the variable cancer incidence among these mouse strains may be due in part to differential cytosine methylation in critical tumor suppressor genes and other regulatory regions of the genome that affect associated pathways for liver cancer susceptibility and its heritability across generations.
Two mouse strains and their offspring will be measured. Once the methylation locations are defined, the information will be placed in a publicly-accessible database on the Internet, together with suitable computer programs allowing scientists and the general public to inspect these sequences and further explore the linkage between the methylome and the appearance of liver diseases, including cancers.
Research Management and Support (RMS)
The RMS program provides administrative, budgetary, logistical and scientific support in the review, award, and monitoring of research grants and training awards. NIEHS currently oversees approximately 785 research grants and centers. RMS also provides administrative support for the Intramural Research program. Other RMS functions include strategic planning, coordination, and evaluation of NIEHS programs, regulatory compliance, ethics, and liaison with other Federal agencies, Congress, and the public. NIEHS has been conducting an inclusive strategic planning process for almost a year; the resulting Strategic Plan and Goals, due to be completed this summer, will define the Institute’s directions for the next five years.
Budget Policy: The FY 2013 President’s Budget request for this program is $23.773 million, the same as the FY 2012 Enacted level. Resources continue to support liaison functions with other government agencies and non-government organizations to improve interagency collaboration and efficiency and optimize use of resources.
1. American Heart Association. Heart disease and stroke statistics—2011 update. (cited 2011 December 2)
3. Barr FD, Krohmer LJ, Hamilton JW, Sheldon LA. Disruption of histone modification and CARM1 recruitment by arsenic represses transcription at glucocorticoid receptor-regulated promoters. PLoS One. 2009 Aug 26;4(8):e6766.
4. Ke Q, Davidson T, Chen H, Kluz T, Costa M. Alterations of histone modifications and transgene silencing by nickel chloride. Carcinogenesis. 2006 Jul;27(7):1481-8. Epub 2006 Mar 7.
5. Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK. Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS One. 2010 Sep 30;5(9). pii: e13100.
6. Koturbash I, Scherhag A, Sorrentino J, Sexton K, Bodnar W, Tryndyak V, Latendresse JR, Swenberg JA, Beland FA, Pogribny IP, Rusyn I. Epigenetic alterations in liver of C57BL/6J mice after short-term inhalational exposure to 1,3-butadiene.
7. Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, Tenesa A, Kusel VI, Sheehan P, Eaaswarkhanth M, Yearout D, Samii A, Roberts JW, Agarwal P, Bordelon Y, Park Y, Wang L, Gao J, Vance JM, Kendler KS, Bacanu SA, Scott WK, Ritz B, Nutt J, Factor SA, Zabetian CP, Payami H. Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson’s disease modifier gene via interaction with coffee. PLoS Genet. 2011 Aug;7(8):e1002237. Epub 2011 Aug 18
8. Tokar EJ, Qu W, Waalkes MP. Arsenic, stem cells, and the developmental basis of adult cancer. Toxicol Sci. 2011 Mar;120 Suppl 1:S192-203.
9. Tokar EJ, Qu W, Waalkes MP. Arsenic, stem cells, and the developmental basShi X, von dem Bussche A, Hurt RH, Kane AB, Gao H. Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation. Nat Nanotechnol. 2011 Sep 18. doi: 10.1038/nnano.2011.151.
10. Krishnan S, Wasalathanthri D, Zhao L, Schenkman JB, Rusling JF. Efficient bioelectronics actuation of the natural catalytic pathway of human metabolic cytochrome P450s. dx.doi.org/10.1021/ja108637s | J. Am. Chem. Soc. 2011, 133, 1459–1465
11. Krishnan S, Schenkman JB, Rusling JF. Bioelectronic delivery of electrons to cytochrome P450 enzymes. J Phys Chem B. 2011 Jul 7;115(26):8371-80. Epub 2011 May 17.
12. Poole JA, Kielian T, Wyatt TA, Gleason AM, Stone J, Palm K, West WW, Romberger DJ. Organic dust augments nucleotide-binding oligomerization domain expression via an NF-{kappa}B pathway to negatively regulate inflammatory responses. Am J Physiol Lung Cell Mol Physiol. 2011 Sep;301(3):L296-306.
13. Wang, X., Hawkins, B. T., Miller, D. S. Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. FASEB J. 25, 644–652 (2011).
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