Integrating Multiscale Geospatial Environmental Data into Large Population Health Studies: Challenges and Opportunities.

Quantifying the exposome is key to understanding how the environment impacts human health and disease. However, accurately, and cost-effectively quantifying exposure in large population health studies remains a major challenge. Geospatial technologies offer one mechanism to integrate high-dimensional environmental data into epidemiology studies, but can present several challenges. In June 2021, the National Institute of Environmental Health Sciences (NIEHS) held a workshop bringing together experts in exposure science, geospatial technologies, data science and population health to address the need for integrating multiscale geospatial environmental data into large population health studies. The primary objectives of the workshop were to highlight recent applications of geospatial technologies to examine the relationships between environmental exposures and health outcomes; identify research gaps and discuss future directions for exposure modeling, data integration and data analysis strategies; and facilitate communications and collaborations across geospatial and population health experts. This commentary provides a high-level overview of the scientific topics covered by the workshop and themes that emerged as areas for future work, including reducing measurement errors and uncertainty in exposure estimates, and improving data accessibility, data interoperability, and computational approaches for more effective multiscale and multi-source data integration, along with potential solutions.

Sharing SRP data to reduce environmentally associated disease and promote transdisciplinary research.

The National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research and Training Program (SRP) funds a wide range of projects that span biomedical, environmental sciences, and engineering research and generate a wealth of data resulting from hypothesis-driven research projects. Combining or integrating these diverse data offers an opportunity to uncover new scientific connections that can be used to gain a more comprehensive understanding of the interplay between exposures and health. Integrating and reusing data generated from individual research projects within the program requires harmonization of data workflows, ensuring consistent and robust practices in data stewardship, and embracing data sharing from the onset of data collection and analysis. We describe opportunities to leverage data within the SRP and current SRP efforts to advance data sharing and reuse, including by developing an SRP dataset library and fostering data integration through Data Management and Analysis Cores. We also discuss opportunities to improve public health by identifying parallels in the data captured from health and engineering research, layering data streams for a more comprehensive picture of exposures and disease, and using existing SRP research infrastructure to facilitate and foster data sharing. Importantly, we point out that while the SRP is in a unique position to exploit these opportunities, they can be employed across environmental health research. SRP research teams, which comprise cross-disciplinary scientists focused on similar research questions, are well positioned to use data to leverage previous findings and accelerate the pace of research. Incorporating data streams from different disciplines addressing similar questions can provide a broader understanding and uncover the answers to complex and discrete research questions.

Expanding the Concept of Translational Research: Making a Place for Environmental Health Sciences.

SUMMARY: The National Institute of Environmental Health Sciences (NIEHS) introduces a new translational research framework that builds upon previous biomedical models to create a more comprehensive and integrated environmental health paradigm. The framework was developed as a graphical construct that illustrates the complexity of designing, implementing, and tracking translational research in environmental health. We conceptualize translational research as a series of concentric rings and nodes, defining "translation" as movement either from one ring to another or between nodes on a ring. A "Fundamental Questions" ring expands upon the research described in other frameworks as "basic" to include three interrelated concepts critical to basic science research: research questions, experimental settings, and organisms. This feature enables us to capture more granularity and thus facilitates an approach for categorizing translational research and its growth over time. We anticipate that the framework will help researchers develop compelling long-term translational research stories and accelerate public health impacts by clearly mapping out opportunities for collaborations. By using this paradigm, researchers everywhere will be better positioned to design research programs, identify research partners based on cross-disciplinary research needs, identify stakeholders who are likely to use the research for environmental decision-making and intervention, and track progress toward common goals. https://doi.org/10.1289/EHP3657.

The Children's Health Exposure Analysis Resource: enabling research into the environmental influences on children's health outcomes.

PURPOSE OF REVIEW: The Children's Health Exposure Analysis Resource (CHEAR) is a new infrastructure supported by the National Institute of Environmental Health Sciences to expand the ability of children's health researchers to include analysis of environmental exposures in their research and to incorporate the emerging concept of the exposome. RECENT FINDINGS: There is extensive discussion of the potential of the exposome to advance understanding of the totality of environmental influences on human health. Children's health is a logical choice to demonstrate the exposome concept due to the extensive existing knowledge of individual environmental exposures affecting normal health and development and the short latency between exposures and observable phenotypes. Achieving this demonstration will require access to extensive analytical capabilities to measure a suite of exposures through traditional biomonitoring approaches and to cross-validate these with emerging exposomic approaches. SUMMARY: CHEAR is a full-service exposure assessment resource, linking up-front consultation with both laboratory and data analysis. Analyses of biological samples are intended to enhance studies by including targeted analysis of specific exposures and untargeted analysis of small molecules associated with phenotypic endpoints. Services provided by CHEAR are made available without cost but require a brief application and adherence to policies detailed on the CHEAR web page at https://chearprogram.org/.

Toward Greater Implementation of the Exposome Research Paradigm within Environmental Epidemiology.

Investigating a single environmental exposure in isolation does not reflect the actual human exposure circumstance nor does it capture the multifactorial etiology of health and disease. The exposome, defined as the totality of environmental exposures from conception onward, may advance our understanding of environmental contributors to disease by more fully assessing the multitude of human exposures across the life course. Implementation into studies of human health has been limited, in part owing to theoretical and practical challenges including a lack of infrastructure to support comprehensive exposure assessment, difficulty in differentiating physiologic variation from environmentally induced changes, and the need for study designs and analytic methods that accommodate specific aspects of the exposome, such as high-dimensional exposure data and multiple windows of susceptibility. Recommendations for greater data sharing and coordination, methods development, and acknowledgment and minimization of multiple types of measurement error are offered to encourage researchers to embark on exposome research to promote the environmental health and well-being of all populations.

Informatics and Data Analytics to Support Exposome-Based Discovery for Public Health.

The complexity of the human exposome-the totality of environmental exposures encountered from birth to death-motivates systematic, high-throughput approaches to discover new environmental determinants of disease. In this review, we describe the state of science in analyzing the human exposome and provide recommendations for the public health community to consider in dealing with analytic challenges of exposome-based biomedical research. We describe extant and novel analytic methods needed to associate the exposome with critical health outcomes and contextualize the data-centered challenges by drawing parallels to other research endeavors such as human genomics research. We discuss efforts for training scientists who can bridge public health, genomics, and biomedicine in informatics and statistics. If an exposome data ecosystem is brought to fruition, it will likely play a role as central as genomic science has had in molding the current and new generations of biomedical researchers, computational scientists, and public health research programs.

Biomonitoring in the Era of the Exposome.

BACKGROUND: The term "exposome" was coined in 2005 to underscore the importance of the environment to human health and to bring research efforts in line with those on the human genome. The ability to characterize environmental exposures through biomonitoring is key to exposome research efforts. OBJECTIVES: Our objectives were to describe why traditional and nontraditional (exposomic) biomonitoring are both critical in studies aiming to capture the exposome and to make recommendations on how to transition exposure research toward exposomic approaches. We describe the biomonitoring needs of exposome research and approaches and recommendations that will help fill the gaps in the current science. DISCUSSION: Traditional and exposomic biomonitoring approaches have key advantages and disadvantages for assessing exposure. Exposomic approaches differ from traditional biomonitoring methods in that they can include all exposures of potential health significance, whether from endogenous or exogenous sources. Issues of sample availability and quality, identification of unknown analytes, capture of nonpersistent chemicals, integration of methods, and statistical assessment of increasingly complex data sets remain challenges that must continue to be addressed. CONCLUSIONS: To understand the complexity of exposures faced throughout the lifespan, both traditional and nontraditional biomonitoring methods should be used. Through hybrid approaches and the integration of emerging techniques, biomonitoring strategies can be maximized in research to define the exposome.

The Importance of the Biological Impact of Exposure to the Concept of the Exposome.

BACKGROUND: The term "exposome" was originally coined in 2005 and defined as the totality of exposures throughout the lifetime. The exposome provides an excellent scientific framework for studying human health and disease. Recently, it has been suggested that how exposures affect our biology and how our bodies respond to such exposures should be part of the exposome. OBJECTIVES: The authors describe the biological impact of the exposome and outline many of the targets and processes that can be assessed as part of a comprehensive analysis of the exposome. DISCUSSION: The processes that occur downstream from the initial interactions with exogenous and endogenous compounds determine the biological impact of exposures. If the effects are not considered in the same context as the exposures, it will be difficult to determine cause and effect. The exposome and biology are interactive-changes in biology due to the environment change one's vulnerability to subsequent exposures. Additionally, highly resilient individuals are able to withstand environmental exposures with minimal effects to their health. We expect that the vast majority of exposures are transient, and chemicals underlying exposures that occurred weeks, months, or years ago are long gone from the body. However, these past chemical exposures often leave molecular fingerprints that may be able to provide information on these past exposures. CONCLUSIONS: Through linking exposures to specific biological responses, exposome research could serve to improve understanding of the mechanistic connections between exposures and health to help mitigate adverse health outcomes across the lifespan. CITATION: Dennis KK, Auerbach SS, Balshaw DM, Cui Y, Fallin MD, Smith MT, Spira A, Sumner S, Miller GW. 2016. The importance of the biological impact of exposure to the concept of the exposome. Environ Health Perspect 124:1504-1510; http://dx.doi.org/10.1289/EHP140.

Mitochondria, energetics, epigenetics, and cellular responses to stress.

BACKGROUND: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria-nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. OBJECTIVES: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. METHODS: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25-26 March 2013. Here, we summarize key points and ideas emerging from this meeting. DISCUSSION: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. CONCLUSIONS: Understanding mitochondria-cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors.

ONE Nano: NIEHS's strategic initiative on the health and safety effects of engineered nanomaterials.

BACKGROUND: The past decade has seen tremendous expansion in the production and application of engineered nanomaterials (ENMs). The unique properties that make ENMs useful in the marketplace also make their interactions with biological systems difficult to anticipate and critically important to explore. Currently, little is known about the health effects of human exposure to these materials. OBJECTIVES: As part of its role in supporting the National Nanotechnology Initiative, the National Institute of Environmental Health Sciences (NIEHS) has developed an integrated, strategic research program-"ONE Nano"-to increase our fundamental understanding of how ENMs interact with living systems, to develop predictive models for quantifying ENM exposure and assessing ENM health impacts, and to guide the design of second-generation ENMs to minimize adverse health effects. DISCUSSION: The NIEHS's research investments in ENM health and safety include extramural grants and grantee consortia, intramural research activities, and toxicological studies being conducted by the National Toxicology Program (NTP). These efforts have enhanced collaboration within the nanotechnology research community and produced toxicological profiles for selected ENMs, as well as improved methods and protocols for conducting in vitro and in vivo studies to assess ENM health effects. CONCLUSION: By drawing upon the strengths of the NIEHS's intramural, extramural, and NTP programs and establishing productive partnerships with other institutes and agencies across the federal government, the NIEHS's strategic ONE Nano program is working toward new advances to improve our understanding of the health impacts of engineered nanomaterials and support the goals of the National Nanotechnology Initiative.

Research strategies for safety evaluation of nanomaterials, Part III: nanoscale technologies for assessing risk and improving public health.

Risk assessment in the environmental health sciences focuses on understanding the nature of environmental exposures and the potential harm posed by those exposures which in turn is determined by the perturbation of biological pathways and the individual's susceptibility to damage. While there are extensive research efforts ongoing in these areas, progress in each is currently slowed by technological limitations including comprehensive assessment of multiple exposures in real time and dynamic assessment of biological response with high temporal and quantitative resolution. This Forum article discusses recent technological innovations capitalizing on the emergent properties of nanoscale materials and their potential adaptation to improving individual exposure assessment, determination of biological response, and environmental remediation. The ultimate goal is to raise the environmental health science community's awareness of these possibilities and encourage the development of improved strategies for assessing risk and improving public health.