Attachment 3B DERT Briefing Book.pdf

National Institute of Environmental Health Sciences

Division of Extramural Research and Training (DERT)

OVERVIEW AND

HIGHLIGHTS

MAY 2018

Attachment 3B

DERT BRIEFING BOOK

ii

Table of Contents

FOREWORD

NIEHS ORGANIZATION AT A GLANCE

DIVISION OF EXTRAMURAL RESEARCH AND TRAINING OVERVIEW

DERT ORGANIZATION CHART

DERT’S EIGHT BRANCHES

RESEARCH ACTIVITIES: ENVIRONMENTAL EXPOSURE RESEARCH

Air Pollution Endocrine Disrupting Chemicals The Exposome and Exposure Biology Mixtures

RESEARCH ACTIVITIES: HEALTH IMPACTS RESEARCH

Autism Spectrum Disorder Cancer and the Environment Children’s Environmental Health Developmental Origins of Health and Disease DNA Damage Response and Genome Integrity Environmental Epigenetics Immunology, Autoimmunity, and the Microbiome Mitochondrial Dysfunction Neurodegenerative Diseases Neurodevelopmental Diseases Obesity, Diabetes, Metabolic Disease, and Nutrition Reproductive System Disorders

CENTERS, INTERAGENCY COLLABORATIONS, AND CONSORTIA

Breast Cancer and the Environment Research Program Centers of Excellence on Environmental Health Disparities Research Children’s Environmental Health and Disease Prevention Research Centers Children’s Health Exposure Analysis Resource Climate Change and Human Health Countermeasures Against Chemical Threats (Counteract) Deepwater Horizon Research Consortia Environmental Health Sciences Core Centers Nanotechnology Environmental Health and Safety Oceans and Human Health Superfund Research Program

TRANSLATIONAL SCIENCE, OUTREACH, AND EDUCATION

Partnerships for Environmental Public Health (PEPH) Small Business Programs (SBIR/STTR) Virtual Consortium For Translational/Transdisciplinary Environmental Research (ViCTER) Worker Training Program

PROGRAM ANALYSIS

PROFESSIONAL TRAINING AND CAREER ENHANCEMENT

GRANT PROCESS OVERVIEW

FOREWORD

The mission of the National Institute of Environmental Health Sciences (NIEHS) is to discover how the environment affects people in order to promote healthier lives. Of the 27 research Institutes and Centers that comprise the National Institutes of Health (NIH), NIEHS is most focused on preventing rather than diagnosing health issues. The more we know about environmental exposures and how they affect health outcomes, the greater our ability to create healthy environments by reducing or preventing hazardous exposures.

The NIEHS research agenda is based on the concept that all complex diseases have both an environmental and a genetic component. Our research programs cover the effects of environmental exposures throughout the lifespan, from preconception to old age. We fund studies using computational and cell-based models; fish, amphibian, and mammalian models; and epidemiological studies with human participants.

During the past five years, our work has been guided by our 2012–2017 Strategic Plan, Advancing Science, Improving Health: A Plan for Environmental Health Research. In constructing this plan, we collected the input and expertise of the environmental health science (EHS) community and NIEHS’s many other stakeholders.

The result was a plan that has led not only NIEHS, but the entire field of EHS, to new achievements in knowledge, technologies, approaches, and interventions to address environmental health challenges.

Implementation of the 2012-2017 Strategic Plan was truly an Institute-wide effort. In the Division of Extramural Research and Training (DERT), strategic goal implementation teams made up of DERT staff were essential to establishing and maintaining the momentum necessary to achieve short- and long-term objectives for each goal.

As we reflect on the past five years, there are many accomplishments that showcase how DERT turned strategic directives into action and outcomes. For example, DERT helped organize and sponsor 126 meetings and webinars related to strategic goals; and DERT staff contributed to 30 publications resulting from these NIEHS-supported events. We also issued 52 funding opportunity announcements to promote research in strategic goal areas. By establishing 54 external collaborations focused on strategic goals, we brought new perspectives and voices to the table. Finally, we created 25 resources and tools to help the grantee community embrace the strategic goals, including the Children’s Health Exposure Analysis Resource (CHEAR), the Epidemiology Resources Web tool, and the Web-based Environmental Health Economic Analysis Annotated Bibliography.

Together, NIEHS and the environmental health science community have made great progress in identifying and understanding the role of the environment in health and disease. NIEHS-supported investigators are determining how environmental agents cause or exacerbate a variety of human diseases and disorders.

We are investigating important biological processes—for example, the microbiome and inflammation pathways, immunological pathways, nutrition, and epigenetic processes—all of which change with environmental exposures. We support important work aimed at understanding environmental health contributions to children’s health, healthy aging, and health disparities. NIEHS-funded research is also defining the “exposome,” which is the totality of exposure encountered by humans. NIEHS has also advanced exposure science by supporting new technologies for sensor devices and big data approaches to analyzing exposure data.

After the publication of research findings, NIEHS helps translate environmental health research into action through public health interventions, policies, and preventive clinical practice. Through training and education along with communication and engagement, we are implementing the NIEHS vision to provide global leadership for innovative research that improves public health by preventing disease and disability.

Gwen Collman, Ph.D.

Director, Division of Extramural Research and Training National Institute of Environmental Health Sciences https://www.niehs.nih.gov/about/strategicplan/strategicplan2012/index.cfm https://www.niehs.nih.gov/about/strategicplan/strategicplan2012/index.cfm https://chearprogram.org/ https://chearprogram.org/ https://www.niehs.nih.gov/research/supported/cohort/ https://www.niehs.nih.gov/research/resources/eheaNIEHS/ehea/index.cfm https://www.niehs.nih.gov/research/resources/eheaNIEHS/ehea/index.cfm

NIEHS ORGANIZATION AT A GLANCE

Division of Intramural Research

Darryl C. Zeldin, M.D.

Scientific Director

Clinical Research Branch

Janet Hall, M.D., M.S.

Director

Office of the Deputy Director Richard Woychik, Ph.D.

Deputy Director, NIEHS

Office of Management

Chris Long, M.P.A.

Executive Officer

Division of the National Toxicology Program

Brian Berridge, D.V.M., Ph.D.

Director

Division of Extramural

Research and Training

Gwen W. Collman, Ph.D.

Director

J. Patrick Mastin, Ph.D.

Deputy Director

Office of the Director

Linda Birnbaum, Ph.D., D.A.B.T., A.T.S.

Director, NIEHS and NTP

DIVISION OF EXTRAMURAL RESEARCH AND TRAINING

OVERVIEW

The NIEHS funds a substantial portfolio of extramural research in the field of environmental health sciences conducted by investigators in many disciplines from various agencies, universities, and organizations.

The extramural research activities described in this booklet span a wide range of topic areas, ranging from basic molecular biology to population-based and clinical research.

Overall, there are three basic extramural functions—scientific program administration, grants management, and scientific review— undertaken by the Division of Extramural Research and Training (DERT). These functions are accomplished through the collective work of eight branches, with support from staff within the Office of the Director. This Division also helps assure maximum utilization of available resources in attainment of the objectives stated in the NIEHS Strategic Plan.

DERT staff plans, reviews, approves, directs, fiscally administers, and evaluates performance of the Institute’s grant, cooperative agreement, and contract programs, all of which support research and training in environmental health science. The Division develops program priorities and recommends funding levels to assure that available resources are used effectively to attain Institute objectives. By staying abreast of national and international research efforts and priorities, the staff identifies and assesses the need for research and training in environmental health science and identifies new opportunities for collaborative initiatives. Collaborative relationships are formed and maintained with people in other NIH Institutes, other federal agencies, and private organizations.

DERT OFFICE OF THE DIRECTOR

Under the direction of Gwen Collman, Ph.D., staff in the Office of the Director oversee and coordinate all scientific, programmatic, and administrative activities of the Division, as well as conduct functions related to oversight of the National Advisory Environmental Health Sciences (NAEHS) Council. Patrick Mastin, Ph.D., serves as Deputy Director for DERT.

This office directs scientific activities across the field of environmental health sciences. Staff provide cross-divisional services in areas such as program and project administration, tracking, analysis, budget, and management.

Staff:

■ Gwen Collman, Ph.D., Director

■ Patrick Mastin, Ph.D., Deputy Director

■ Liz McNair, Program Analyst

■ Nicole Popovich, Management Analyst

■ Angela Sanders, Lead Administrative Officer

■ Helena Bonner, Administrative Officer

■ Bryan A. Duran, Administrative Specialist

■ Katherine A. Fine, Administrative Officer

■ Liz McMillan, Administrative Technician

■ Mitsue Parrish, Administrative Officer

■ Tina Powell, Executive Assistant

DERT ORGANIZATION CHART

Exposure, Response, and Technology Branch David Balshaw, Ph.D., Branch Chief

Genes, Environment, and Health Branch Cindy Lawler, Ph.D., Branch Chief

Hazardous Substances Research Branch William Suk, Ph.D., Branch Chief

D E

R T

O ff ic e o f th e

D ir ec to r

Program Analysis Branch Christina Drew, Ph.D., Branch Chief

Worker Education and Training Branch Joseph (Chip) Hughes, Jr., Branch Chief

Scientific Review Branch Alfonso R. Latoni, Ph.D., Branch Chief

Population Health Branch Claudia Thompson, Ph.D., Branch Chief

Grants Management Branch George Tucker, Branch Chief

DERT’S EIGHT BRANCHES

EXPOSURE, RESPONSE, AND TECHNOLOGY BRANCH

The Exposure, Response, and Technology Branch (ERTB) plans, develops, and administers research grants, contracts, and cooperative agreements that address the relationship between environmental exposures and biological response. ERTB focuses on the development of technologies and infrastructures that can improve our understanding of the complexity of the personal environment and biological response on a systems level. It stimulates research on emerging areas of fundamental mechanisms of biological response such as the influence of exposures on the translational control of protein synthesis. As part of the Branch’s efforts to build capacity in the environmental health sciences, it oversees NIEHS extramural efforts in both research infrastructure, and training and career development.

Staff:

■ David Balshaw, Ph.D., Branch Chief

Development, validation, and application of emerging technologies for exposure assessment; exposure biology and the exposome concept; development of ‘omics technologies; translational control of protein synthesis

■ Jennifer Collins, M.R., Health Specialist Nanotechnology Consortia, CHEAR, exposure biology, contract management, portfolio analysis and evaluation

■ Yuxia Cui, Ph.D., Contractor – Program Analyst Exposure biology and the exposome, toxicogenomics, molecular toxicology, portfolio analysis and evaluation

■ Srikanth Nadadur, Ph.D., Health Scientist Administrator Air pollution and respiratory health, environmental health and safety of nanotechnology, Nanotechnology Consortia, CounterACT

■ Lingamanaidu (Ravi) V. Ravichandran, Ph.D., Health Specialist Small business programs, cardiovascular and metabolic disease research, scientific writing

■ Les Reinlib, Ph.D., Health Scientist Administrator Genome integrity and environmental carcinogenesis, stem cell biology and tissue engineering, breast cancer biology

■ Daniel Shaughnessy, Ph.D., Health Scientist Administrator Genome integrity and mutagenesis, biomarker discovery and validation, mitochondrial biology, Small Business Programs

■ Carol Shreffler, Ph.D., Health Scientist Administrator Training and Career Development Programs; liver, kidney, and digestive disease research https://www.niehs.nih.gov/research/supported/dert/ertb/index.cfm

GENES, ENVIRONMENT, AND HEALTH BRANCH

The Genes, Environment, and Health Branch (GEHB) plans, develops, and administers research grants, contracts, and cooperative agreements related to genetic susceptibility to environmental exposures, as gene-environment interactions are directly responsible for most complex human diseases. Programs supported by GEHB emphasize laboratory-based studies in model systems at the molecular, cellular, organ, and system level as well as integrative research programs that span basic, clinical, and translational activities.

Staff:

■ Cindy Lawler, Ph.D., Branch Chief

Autism, Big Data to Knowledge (BD2K)

■ Lisa Chadwick, Ph.D., Health

Scientist Administrator AREA (R15) Grant Coordinator, aryl hydrocarbon receptor biology, NIH Roadmap Epigenomics Program,4D Nucleome Program, International Human Epigenome Consortium, TaRGET Program, environmental epigenetics (human), transgenerational inheritance, microbiome, non-mammalian models

■ Christopher Duncan, Ph.D., Health Scientist Administrator Data science, bioinformatics, epigenomics

■ Amanda Garton, Health Specialist Program support and analysis

■ Astrid Haugen, Health Specialist Summer Research Experience Program Administrator, Loan Repayment Program Liaison, Autism and the Environment Program, Data Science Programs

■ Jonathan Hollander, Ph.D., Health Scientist Administrator Neurodegeneration, neurodevelopmental toxicology (other than autism), neuroscience, brain imaging, NIH Blueprint for Neuroscience Research Program, ViCTER

■ Michael Humble, Ph.D., Health Scientist Administrator Skin disease, immunotoxicology and autoimmune disease, Fellowship Program Coordinator, R25 Research Education Programs, Global Environmental and Occupational Health (GEOHealth) Program

■ Kimberly McAllister, Ph.D., Health Scientist Administrator Human genetics and genetic epidemiology, DNA repair and genomic stability, animal models of human disease, comparative biology approaches, statistical and bioinformatics methods for gene-environment interactions, Roadmap Epigenomics Mapping Consortium

■ Frederick L. Tyson, Ph.D., Health Scientist Administrator Environmental epigenetics (fundamental mechanisms, non-human models), TaRGET Program, Oceans and Human Health Program, lung cancer, FDA-NIH Tobacco Science Research Program, NIH Roadmap Epigenomics Program, apoptosis https://www.niehs.nih.gov/research/supported/dert/geh/index.cfm

HAZARDOUS SUBSTANCES RESEARCH BRANCH

The Hazardous Substances Research Branch (HSRB) supports basic and applied research in the biomedical and environmental sciences and engineering to address health consequences related to exposure to hazardous substances in the environment. Supports all activities of the Superfund Research Program (SRP), which funds multidisciplinary research that addresses the broad, complex human health issues surrounding hazardous substances. More detail about SRP is found later in this document. HSRB also coordinates global environmental health and sustainable development activities. It further enhances collaborations with institutions abroad to understand the effects of, measure, or reduce exposures, primarily in vulnerable populations; develops innovative technologies for the prevention of such exposures; and translates research results into application to be used for informed decision-making processes.

Staff:

■ William A. Suk, Ph.D., M.P.H., Branch Chief

Director, SRP

■ Danielle Carlin, Ph.D., D.A.B.T., Health

Scientist Administrator SRP, xenobiotic metabolism, chemical mixtures, combined exposures, metals, inhalation toxicology

■ Michelle Heacock, Ph.D., Health Scientist Administrator SRP, exposure biology, telomere stability, genome integrity and environmental mutagenesis

■ Heather Henry, Ph.D., Health Scientist Administrator SRP, human health toxicology, risk assessment, detection technologies and remediation approaches, including plant-based environmental remediation

■ Rosemary Moody, Extramural Support Assistant

■ Brittany Trottier, M.P.H. Candidate, Health Specialist SRP, Data analysis for NIEHS/SRP CareerTrac, Data Science, Small Business/Technology Transfer Grant Projects https://www.niehs.nih.gov/research/supported/dert/hsrb/index.cfm

POPULATION HEALTH BRANCH

The Population Health Branch (PHB) develops and administers research grants, contracts, and cooperative agreements that use population, laboratory, and community-based approaches related to environmental exposure and its effect on individual and population health. PHB focuses on laboratory-based and epidemiologic studies that define and elucidate relationships between exposure during sensitive life stages and disease risk. It also supports research programs that include community-based interventions and prevention; environmental public health research that relates to health disparities and environmental justice; and trans-disciplinary approaches that integrate and span basic, clinical, and translational activities.

Staff:

■ Claudia Thompson, Ph.D., Branch Chief

Environmental Health Sciences Core Center Director, Deepwater Horizon Research Consortia, household air pollution/ cookstoves, CHEAR

■ Martha Barnes, M.S., Program Analyst R13/U13 Conference Grants and Time-Sensitive Research programs, human subjects protection, gender/minority inclusion monitoring, certificates of confidentiality, portfolio analysis

■ Abee Boyles, Ph.D. Health Scientist Administrator Systematic review, literature-based environmental health science assessments

■ Symma Finn, Ph.D., Health Scientist Administrator Social and behavioral research, health disparities, environmental health literacy and STEM education, data sharing, Deepwater Horizon Research Consortia, Breast Cancer and the Environment Research Program, PEPH, Research to Action, children’s respiratory, climate change

■ Kimberly Gray, Ph.D., Health Scientist Administrator Centers for Children’s Environmental Health and Disease Prevention Research, CHEAR, Environment Influences on Children’s Health Outcomes (ECHO), pediatric environmental epidemiology, neuroepidemiology, Senior Advisor-Certificates of Confidentiality

■ Bonnie R. Joubert, Ph.D., Health Scientist Administrator Environmental epidemiology, respiratory and cardiovascular epidemiology, obesity/diabetes, chemical mixtures, immunotoxicity

■ Linette Mines, Extramural Support Assistant

■ Liam O’Fallon, M.A., Health Scientist

PEPH, environmental justice, science education, community-engaged research, environmental health literacy

■ Thaddeus Schug, Ph.D., Health Scientist Administrator Reproductive health; Consortium Linking Academic and Regulatory Insights on Bisphenol A (BPA) Toxicity Program; endocrine disruptors; BPA Research Program;

cardiovascular diseases, DOHaD, obesity, diabetes, metabolic disease, and nutrition https://www.niehs.nih.gov/research/supported/dert/phb/index.cfm

WORKER EDUCATION AND TRAINING BRANCH

The Worker Education and Training Branch (WETB) supports the prevention of work-related harm through the education and training of workers and their communities in environmental health, focusing on safety concerns related to hazardous materials and waste generation, removal, containment, transportation, and emergency response. WETB also supports the National Clearinghouse for Worker Safety and Health Training, which is the primary national source for hazardous waste worker curricula, technical reports, and weekly news on hazardous materials, waste operations, and emergency response. More detailed information about the Worker Training Program (WTP) is found later in this document.

Staff:

■ Joseph T. Hughes, Jr, M.P.H., Branch Chief and Program Director

■ Kathy Ahlmark, Program Analyst

Program Administrator of the WTP SBIR program to support computer and web-based training for hazardous waste workers and emergency responders, Contracting Officer Technical Representative for the National Clearinghouse on Worker Safety and Health Training

■ Sharon Beard, M.S., CIH, Industrial Hygienist Coordinates, evaluates, and improves the nation-wide worker education and training program, especially the Minority Worker Training Program initiative

■ Carolina Medina, Extramural Support Assistant

■ James Remington, R.N., Program Analyst Manages a portfolio of hazardous material training and SBIR grants, oversees disaster response activities

■ Demia S. Wright, M.P.H., Public Health Educator Administers cooperative agreements under the Hazardous Waste Worker Training Program, provides health education expertise to WTP in the areas of program evaluation, communications, and adult learning https://www.niehs.nih.gov/research/supported/dert/wet/index.cfm

PROGRAM ANALYSIS BRANCH

The Program Analysis Branch (PAB) communicates the impact of DERT-supported programs and grant portfolios by providing independent evaluation and analysis, as well as developing the methodologies, data structures, and information technologies necessary to conduct program analyses. More detail about the work of PAB is found later in this document.

Staff:

■ Christie Drew, Ph.D., Branch Chief

Program evaluation, tool development (High Impacts Tracking System, CareerTrac), portfolio analysis, metrics, communication

■ Joel Collinson, Extramural Support Assistant Support documentation for CareerTrac and the High Impacts Tracking System, database query, travel, administration

■ Sarah Luginbuhl, Program Analyst (Contractor) Program manager for CareerTrac, trainee tracking, portfolio tracking and analysis

■ Helena Kennedy, Program Analyst IMPAC II Coordinator, DERT website development, data mining, portfolio tracking and analysis, Supplement Operation Systems development, DERT Science and Research Program Support (SaRPS)

■ Kristi Pettibone, Ph.D., Health Scientist Administrator Program evaluation, logic models, research and portfolio analysis to inform program decision making

■ Elizabeth Ruben, M.S., Program Analyst DERT Information Technology Liaison, tool development, Grants Application Development Support Contract Manager, multi-dimensional analysis and data visualization, statistical and quantitative analysis

■ Steven Tuyishime, Ph.D., Health Scientist and Presidential Management Fellow Grant coding, portfolio tracking and analysis, program evaluation, molecular biology https://www.niehs.nih.gov/research/supported/dert/pab/index.cfm

GRANTS MANAGEMENT BRANCH

The Grants Management Branch (GMB) provides overall fiscal and administrative management of grants funded through DERT. GMB staff provides expertise in business, fiscal, and other nonscientific areas of grants administration, ensures that NIH and grantee staff fulfill requirements of laws, regulations, and administrative policies, and, when necessary, performs site visits to applicant and grantee organizations for evaluating and monitoring their business management practices. An overview of the grant process is contained in a later section of this document.

Staff:

■ George Tucker, Branch Chief

Grants management, fiscal and administrative management for branch

■ Lisa Edwards, M.B.A., Grants Management Team Lead Team Lead and Senior Specialist for the SRP portfolio

■ Molly Puente, Ph.D., Grants Management Team Lead Manages a wide portfolio of grants for the Population Health Branch and is the Senior Specialist for the Children’s Environmental Health Program

■ Bryann Benton, M.S., Grants Management Officer Manages a variety of research project grants, fellowships grants, and career grants and co-leads the SRP portfolio

■ Barbara Gittleman, M.A., Grants Management Officer Manages a variety of research project grants, NRSA fellowship and training grants, career grants, and cooperative agreements

■ Robbie Majors, M.B.A., Grants Management Specialist Manages a variety of research project grants, NRSA fellowship and training grants, and career grants

■ Aaron Nicholas, Grants Management Officer Manages a broad portfolio of grants for Population Health Branch and is Senior Specialist for the P30 Centers program

■ Barbara Ruffin, Extramural Support Assistant

■ Ashley Singh, M.S., Grants

Management Specialist Manages a variety of research project grants, NRSA fellowship and training grants, and career grants

■ Michelle Victalino, Grants Management Officer Manages a variety of research project grants, NRSA training grants, and co-leads the SRP portfolio

■ James Williams, Grants Management Officer Manages a variety of research project grants, NRSA training grants, fellowships grants, career grants, and is Senior Specialist for Centers for Oceans and Human Health https://www.niehs.nih.gov/research/supported/dert/gmb/index.cfm

SCIENTIFIC REVIEW BRANCH

The Scientific Review Branch (SRB) is responsible for the initial scientific and technical merit review of grant applications and proposals for research and development contracts submitted to the NIEHS.

The Scientific Review Officers (SROs) are extramural staff scientists and the Designated Federal Officials who play a pivotal role in identifying the most meritorious scientific research for support using federal resources. Staff in SRB conduct administrative reviews, identify appropriate scientific peer reviewers, organize review committees and Special Emphasis Panels, oversee and establish the activities of those committees, and develop the Summary Statements and Technical Evaluation Reports that provide reviewer evaluations and recommendations.

Staff:

■ Alfonso R. Latoni, Ph.D., Branch Chief

Social and economic health disparities, social economy and social policy, special populations, aging, and public health policy

■ Janice B. Allen, Ph.D., Scientific Review Officer Scientific review of Outstanding New Environmental Scientist (ONES) R01s, ViCTER R01s, Competitive Revisions, involved in the NIEHS Strategic Plan Inflammation Group

■ Linda K. Bass, Ph.D., Scientific Review Officer Review official for the Environmental Health Sciences Review Committee (EHSRC), Children’s Environmental Health and Disease Prevention Research Centers, and the Breast Cancer Centers

■ Laura A. Thomas, Ph.D., Scientific Review Officer Organizes, manages, and conducts review meetings for multiple mechanisms related to cognitive, behavioral, and neural mechanisms and outcomes of toxic exposures

■ Leroy Worth, Jr., Ph.D., Scientific Review Officer DNA research, neurodevelopment, and neurodegeneration, SRP, Mentored Career Development Awards, Time Sensitive R21s, Research Program R01s, Conferences

■ Kindra Morrison, Extramural Support Assistant

■ Deborah A. Jones, Extramural Support Assistant

■ Sharmice L. Outen, Extramural Support Assistant https://www.niehs.nih.gov/research/supported/dert/srb/index.cfm

RESEARCH ACTIVITIES

ENVIRONMENTAL EXPOSURE RESEARCH

AIR POLLUTION

Air pollution affects people’s health in a variety of ways. These health effects can be seen in the young and old as well as the healthy and infirm. NIEHS is working to understand how air pollution is associated with certain diseases and how to prevent or lessen harm from exposures. With both outdoor and indoor sources, air pollution is a health issue with global consequences.

Air pollution is linked to health problems in the respiratory, cardiovascular, reproductive, neurological, and immune systems. For example, people with asthma can have difficulty breathing if air pollution is high, and prenatal and early childhood air pollution exposure is linked with neurobehavioral problems.

Long-term exposure can cause cancer, and, more recently, scientists have discovered associations with obesity and diabetes.

NIEHS-funded researchers are studying the biological mechanisms that cause and worsen diseases linked to air pollution exposure. They are examining the role that air pollution plays in the development of various diseases, the biological effects of air pollution on the body, and are identifying groups who are most susceptible. Researchers are also studying the combined effects of air pollution and other factors in the indoor and outdoor environments.

Outdoor Air Outdoor air pollutants come from vehicle emissions, factory chimneys, chemical manufacturing, forest fires, and other sources.

NIEHS is funding research on pollutants that include particulate matter, ultrafine particles, ozone, carbon monoxide, nitrogen dioxide, and ozone.

NIEHS research has contributed a sound scientific base for the development of more https://www.niehs.nih.gov/research/supported/exposure/air_pollution/index.cfm stringent air quality standards by regulatory agencies while also contributing to the identification of new risks. As research in this area advances, it will continue to inform public health interventions, including regulatory actions, to improve health and protect quality of life.

Indoor Air Gas stoves and heating units can contribute indoor pollutants such as nitrogen oxide, and indoor mold, tobacco smoke, pet dander, and pest allergens can cause or exacerbate health problems. Many air pollutants created outside can penetrate the indoors and accumulate, especially if buildings have poor ventilation.

NIEHS funds research about the health effects of indoor air pollutants found in homes as well as the workplace, which can include pesticides, ultrafine particles, nanoparticles, and fumes from industrial chemicals.

To better understand how people are affected by air pollution, especially as people move between indoor and outdoor environments, researchers are developing technologies to measure personal exposures and collect data on when and where exposures occurred. They are also considering factors such as a person’s activity levels, which might increase inhalation of pollutants and bring about deeper deposition in the lungs. This work contributes to NIEHS efforts to measure all the exposures a person experiences during a lifetime, a concept known as the exposome.

Global Concerns While all air pollution problems have a global nature, NIEHS also focuses on health problems associated with traditional cookstoves that burn solid fuels, such as wood, crop waste, or dung, and open fires. The smoke from these cooking methods can contain high levels of health-damaging pollutants such as fine particles and carbon monoxide. The NIEHS funds research on cookstoves and their health effects in Ghana, Nepal, Peru, and Nicaragua, among other countries. Scientists are also testing interventions involving less-polluting stove designs and proper ventilation.

Other global factors affecting air pollution are the heat waves and droughts that come with climate change. These meteorological events can greatly alter air quality in places around the world. NIEHS-funded scientists are studying how climate change influences health effects from air pollution.

ENDOCRINE DISRUPTING CHEMICALS

Chemicals known as endocrine disruptors, which can mimic or interfere with hormones in the body, are found in everyday products such as plastic bottles, personal care products, food can liners, solvents, and pesticides.

The ovaries, testes, adrenal glands, thyroid, pituitary gland, and pancreas are all part of the endocrine system, which produces hormones that direct communication and coordinate functions among tissues throughout the body.

The NIEHS is studying a variety of chemicals with endocrine disrupting activity in epidemiology, animal toxicology, and in vitro systems. The majority of the in vivo studies are focused on https://www.niehs.nih.gov/research/supported/exposure/endocrine/index.cfm linking developmental exposures to diseases and dysfunctions that occur across the lifespan.

There are now over 800 chemicals designated as endocrine disruptors. Because endocrine disruptors can interfere with hormone action, there is concern that exposure to these chemicals may increase risk for some cancers, cause male and female reproductive system problems, increase obesity and diabetes, cause learning and memory problems, and play a role in various other diseases and dysfunctions. Although endocrine disruptors can act throughout the lifespan, early life is an especially sensitive time because these chemicals can interfere with epigenetic programming of tissue development leading to increased susceptibility to health outcomes across the lifespan and generations.

Endocrine disruptors that are being studied in

NIEHS funded projects include:

■ Bisphenol A (BPA): found in can linings and cash register receipts

■ Tributyltin and organotins: fungicides

■ Polybrominated diphenyl ethers

(PBDEs): flame retardants used in clothing and furniture

■ Dioxins: byproducts of some manufacturing and incineration processes

■ Phthalates: plasticizers used in plastics and some fragrances and personal-care products

■ Organophosphates and organochlorines:

compounds used in many insecticides, herbicides, and nerve gases

■ Polychlorinated biphenyls (PCBs):

carcinogenic chemicals that persist in the environment even though banned more than 30 years ago

■ Dichlorodiphenyltrichloroethane (DDT):

a pesticide banned in 1972 still found in the environment

■ Perfluorinated chemicals (PFCs):

compounds such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) used to resist stains and absorption of water and oils

■ Polybrominated and other flame retardants: chemicals used in furniture and many consumer products to protect against burning

THE EXPOSOME AND EXPOSURE BIOLOGY

Environmentally related health and disease result from the complexity of a person’s environmental exposures, which arise from a variety of sources. These include both internal factors, such as metabolism, hormones, physical activity, and the microorganisms naturally residing in and on the body (microbiome) and external factors, such as radiation, infectious agents, chemical contaminants, diet, lifestyle factors, and socio-economic stress. The totality of the exposure that a person is subjected to from conception to death is referred to as the exposome, a concept that has become increasingly important for making new discoveries in environmental health.

A better understanding of how the complex nature of a person’s environment contributes to health requires sustained development https://www.niehs.nih.gov/research/supported/exposure/bio/index.cfm of technology for exposure measurement, including better biological markers, new sensor and detector tools, remote detection of exposures, more sensitive analytical methods, and high-throughput predictive pharmacokinetic models as well as informatics tools to improve quantitation of information on exposure from large datasets.

From 2007-2010, research on exposure biology and genetics was coordinated through the Genes, Environment, and Health Initiative to further advance the understanding of gene-environment interplay in human disease. NIEHS remains committed to advancing exposure science and supports many promising research efforts in this area through our investigator-initiated research and small business programs as well as SRP.

The 2012 NIEHS Strategic Plan includes a major goal to promote exposome research by transforming exposure science and creating a blueprint for incorporating exposure science into human health studies. In 2013, NIEHS funded the Health and Exposome Research Center: Understanding Lifetime Exposures (HERCULES) Center at Emory University, which is focused on providing a more comprehensive assessment of environmental influences by using exposome-based concepts and approaches. In 2015, NIEHS launched the Children’s Health Exposure Analysis Resource (CHEAR), a major new infrastructure to provide access to laboratory analyses of biological samples from NIH-funded studies on children’s health and a suite of associated data science tools, including a data repository for exposure measurements and epidemiologic data provided by study principal investigators.

As a leader in the environmental health sciences, NIEHS has been at the forefront of the exposome efforts and is continually committed to proactively engaging the scientific community and creating research opportunities to explore it.

MIXTURES

Most exposure research has studied the health effects of individual chemicals at specific times, but environmental health scientists are developing methods to study environmental exposures in ways that more closely represent the mixture of exposures that we experience in modern life.

Scientists are also working to understand the implications of these complex chemical mixtures, which can sometimes produce health effects greater than each chemical would alone.

For example, exposure to ozone and aldehydes, which are components of smog, produces greater health effects than would be predicted based on each chemical alone. Also, smokers who are also exposed to radon or asbestos have a greater risk of developing lung cancer than non-smokers.

Researchers are examining how mixtures interact using in vitro and in vivo systems and in human studies to determine health effects.

Efforts are being made to develop innovative statistical methods for assessing health effects of mixtures and to characterize real-life exposures. The NIEHS Superfund Research Program also supports research of mixtures on human health and the environment.

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RESEARCH ACTIVITIES

HEALTH IMPACTS RESEARCH

Autism Spectrum Disorder Autism Spectrum Disorder (ASD) affects 1 in 68 children in the United States and about 1.5% of the developed world’s population.

ASD begins early in life, probably during gestation, and causes social impairment and repetitive, restricted behaviors and interests.

The spectrum of ASD encompasses a range of symptoms, skills, and impairment meaning some individuals diagnosed with autism are mildly affected while others are more severely impaired. Medical conditions such as seizure disorders, sleep disturbances, and gastrointestinal problems often occur together with autism. The core symptoms of autism, together with such co-occurring conditions, create enormous challenges for affected people, their families, and society. There is an urgent need for more cutting-edge research as well as new and improved methods of diagnosis, treatments, services, and support across the lifespan.

The extensive phenotypic and genetic heterogeneity observed in ASD suggests there may be many different causes, and evidence points to a role for both genetic and environmental factors. The genetics of ASD are complex; studies have identified contributions from both rare and common variation. In some cases, de novo mutations are observed—such mutations are not inherited from the parents but arise spontaneously in germ cells. Deletion or duplication of stretches of DNA (copy number variation) have also been associated with ASD.

Although the investigation of environmental risks has lagged behind genetic studies, there is a growing appreciation that, in many cases, ASD arises from an interaction of genes and environmental exposures, and that epigenetics may be a central player in mediating such interactions.

Several promising leads by NIEHS Autism Research Program grantees have been uncovered and additional studies that will strengthen the evidence base are underway.

NIEHS research efforts also address priorities identified in the Interagency Autism Coordinating Committee’s Strategic Plan for ASD Research. Some notable emerging findings include links to air pollution as well as the role of immune factors and prenatal nutrients in ASD risk. Other environmental exposures being investigated include endocrine disrupting chemicals (EDCs), pesticides, and metals.

The role of epigenetic changes and gene-environment interactions related to autism are also important areas of study. Understanding the environmental risks of autism may be very beneficial because many environmental factors are modifiable through public health efforts, either through removing or reducing harmful exposures or conditions or increasing factors that confer protection or resilience.

Notable Studies funded by NIEHS CHARGE – The goal of the Childhood Autism Risks from Genetics and the Environment (CHARGE) study is to identify causes and contributing factors for childhood autism. Launched in 2003, this study has enrolled children diagnosed with autism and two comparison groups, children with developmental delays and children with typical development. Information on environmental exposures (e.g., pesticides, phthalates, antibacterials), medical conditions (e.g., gestational diabetes, obesity, inflammation), lifestyle, sociodemographic factors, and behavior continue to be collected from children and their families.

A sampling of peer-reviewed papers include the following results:

■ Exposure to traffic-related air pollution during the first year of life was associated with an increased risk of autism.

■ Folic acid supplements during gestation may decrease the risk of autism.

■ Maternal infection during gestation is associated with an increased risk of having a child with ASD.

MARBLES and EARLI – The Markers of Autism Risk in Babies--Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) studies are following women at high risk of giving birth to a child with autism. Women are enrolled during early pregnancy and their children followed to age three. By collecting data from mothers and their babies throughout critical periods, these studies can better identify early markers that will predict autism and measure environmental exposures (e.g., EDCs, pesticides, maternal infection) that may impact early stages of brain development.

Recent peer-reviewed publications report the following:

■ The placenta could be an informative tissue for identifying children at risk of ASD.

■ Epigenetic differences in paternal sperm may contribute to autism risk in offspring.

CANCER AND THE ENVIRONMENT

It is now clear that most cancer results from an interaction of a person’s genetics with environmental factors. In the United States, environmental factors underlie as much as two thirds of all cancers. In fact, the onset of some forms, such as breast cancer, is likely mostly due to exposure and lifestyle.

The research and public health challenges involved with relating environmental exposures to cancer outcomes include:

■ Investigating windows of susceptibility, or the life periods when individuals may be more vulnerable to exposures that trigger cancer many years later;

■ Accurately monitoring personal exposures and identifying reliable biomarkers;

■ Measuring individual biological https://www.ncbi.nlm.nih.gov/pubmed/23404082 https://www.ncbi.nlm.nih.gov/pubmed/22648721 https://www.ncbi.nlm.nih.gov/pubmed/22562209 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159983/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598797/ responses and accounting for genetic susceptibility; and

■ Determining the mechanisms of carcinogens. This includes working to understand altered gene expression, stem cell changes, DNA damage, and generation of reactive oxygen species.

Some of the key topics in cancer that are being addressed by NIEHS-funded research are:

■ Genome integrity, mutagenesis induced by exposure, and cellular repair of DNA lesions;

■ Stem cells and their growth and transformation;

■ Analyzing the exposome—the totality of exposures throughout the life course—to discover potential exposures associated with carcinogenesis;

■ Development of new tools and measures to determine predisposition to cancer;

■ The role of altered circadian rhythm, which may occur in shift work; and

■ Communicating messages of personal risk and preventive strategies.

CHILDREN’S ENVIRONMENTAL HEALTH

The extensive research program in children’s environmental health at NIEHS is increasing our understanding of environmental exposures and helping to inform the development of protective measures for children in the United States and around the world.

Exposure to contaminants in the womb or during childhood can lead to a variety of health effects, including developmental and behavior problems, childhood diseases, or an increased risk of chronic diseases later in life. Children and the developing fetus are particularly vulnerable to environmental contaminants because their organ, immune, and metabolism systems are still developing. In addition, infants tend to spend a lot of time crawling on the floor and putting their hands in their mouths, which can increase the likelihood of their exposure contaminants.

A broad range of research focuses on contaminants children may encounter, such as metals, endocrine disruptors, complex mixtures of contaminants, as well as pollutants found in the water, air, or food. Researchers are investigating how early life or low dose environmental exposures can have adverse effects on body systems by studying outcomes in children such as autism, attention deficit hyperactivity disorder, cognitive dysfunction, behavior, asthma, neurodevelopment, immune development, sexual maturation, diabetes, obesity, and early cardiovascular changes.

Researchers are seeking to identify biomarkers that could indicate exposure to a chemical or susceptibility to disease. They are also seeking to understand how stress and the social environment may influence the way that environmental exposures affect children’s health. New research areas concern the microbiome, placental epigenetics, and immune dysregulation as potential mechanisms for linking early life exposures to short and long-term diseases and disabilities.

Children’s health research efforts span multiple NIEHS program areas. The Children’s https://www.niehs.nih.gov/research/supported/health/childrens/index.cfm https://www.niehs.nih.gov/research/supported/health/childrens/index.cfm https://www.niehs.nih.gov/research/supported/centers/prevention/index.cfm

Environmental Health and Disease Prevention Research Centers (Children’s Centers), a joint program of the NIEHS and the U.S.

Environmental Protection Agency (EPA), conduct transdisciplinary basic and applied research to examine the effects of environmental factors on child health and promote the well-being of all children.

NIEHS also established the Children’s Health Exposure Analysis Resource (CHEAR) to provide researchers with an expanded range of tools to accurately measure, record, and analyze environmental exposures. Read more about the Children’s Centers and CHEAR in the Centers, Interagency Collaborations, and Consortia section of this booklet.

NIEHS invests in well-characterized cohorts that include pregnant mothers, infants, children, and youth. Studies using these important epidemiology resources are helping to reveal key determinants of environmentally-related diseases and health problems in children.

The Institute is also part of the trans-NIH effort Environmental influences on Child Health Outcomes (ECHO) Program, a seven-year research initiative that will extend and expand existing cohort studies to study how environmental factors affect child health and development.

Environmental exposures pose a serious health risk to millions of children worldwide, especially to those living in low-and middle-income countries. Through its World Health Organization Collaborating Centre for Environmental Health Sciences, NIEHS works with other Collaborating Centres and leading research organizations to address children’s environmental health issues at the local, regional, national, and international levels. Children’s health is also addressed through the NIEHS Global Environmental Health Program, which supports research, research translation, and capacity building in the areas of cookstoves and indoor air pollution, climate change and human health, and global environmental health and sustainable development.

In addition, NIEHS supports a variety of research projects through the National Toxicology Program, the Superfund Research Program, Partnerships for Environmental Public Health, the Powering Research Through Innovative Methods for Mixtures in Epidemiology program, and other programs that apply the latest scientific innovations and approaches to protect children from harmful environmental contaminants.

DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE

Studies of the developmental origins of health and disease (DOHaD) suggest that exposures occurring while tissues and organs are developing increase risk for disease in all stages of life and sometimes in future generations. Diseases and conditions such as obesity, type 2 diabetes, insulin resistance, asthma, cardiovascular diseases, dyslipidemia, cognitive and behavioral disorders, neurodegenerative diseases, some cancers, and reproductive disorders are thought to at least partly result from https://www.niehs.nih.gov/research/supported/centers/prevention/index.cfm https://www.niehs.nih.gov/research/supported/centers/prevention/index.cfm https://www.niehs.nih.gov/research/supported/exposure/chear/index.cfm https://www.niehs.nih.gov/research/supported/exposure/chear/index.cfm https://www.niehs.nih.gov/research/supported/cohort/index.cfm https://www.niehs.nih.gov/research/programs/environmental/index.cfm https://www.niehs.nih.gov/research/programs/geh/partnerships/index.cfm https://www.niehs.nih.gov/research/programs/geh/partnerships/index.cfm https://www.niehs.nih.gov/research/programs/geh/partnerships/index.cfm https://www.niehs.nih.gov/research/programs/geh/index.cfm https://www.niehs.nih.gov/research/programs/geh/index.cfm https://ntp.niehs.nih.gov/ https://ntp.niehs.nih.gov/ https://www.niehs.nih.gov/research/supported/centers/srp/index.cfm…