Gene-environment interactions within a precision environmental health framework.

Understanding the complex interplay of genetic and environmental factors in disease etiology and the role of gene-environment interactions (GEIs) across human development stages is important. We review the state of GEI research, including challenges in measuring environmental factors and advantages of GEI analysis in understanding disease mechanisms. We discuss the evolution of GEI studies from candidate gene-environment studies to genome-wide interaction studies (GWISs) and the role of multi-omics in mediating GEI effects.

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.

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.

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

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.

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.

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.

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.

The Exposome: Embracing the Complexity for Discovery in Environmental Health.

Environmental exposures are ubiquitous and play a fundamental role in the development of complex human diseases. The exposome, which is defined as the totality of environmental exposures over the life course, allows for systematic evaluation of the relationship between exposures and associated biological consequences, and represents a powerful approach for discovery in environmental health research. However, implementing the exposome concept is challenged by the ability to accurately assess multiple exposures and the ability to integrate information across the exposure–disease continuum.

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.

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.

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.

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.

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.