Stage One (Awarded March 2017)
Title: A Novel High Throughput Toxicity Screening System Using Volatilomics
Team: Michael Madden (PI), Michelle Angrish (NHEERL); Joachim Pleil, Ariel Wallace (NERL)
Summary: Environmental chemicals and consumer products have had little or no toxicity evaluations performed due to the testing constraints (time, costs, manpower involved) with standard protocols used and for volatile substances testing methods are nonexistent. To meet these challenges, regulatory agencies are developing high throughput screening (HTS) techniques for in vitro evaluation of chemicals which utilize cells and cell free liquid-based exposure systems to screen for chemical toxicity. These liquid-based HTS approaches cannot assess the toxicity of volatile organic compounds (VOCs). We therefore propose a volatilomics toxicity testing method that would provide the Agency a tool which can evaluate chemical toxicity rapidly and inexpensively.
Title: Big Data and Social Media: A New Lens for Quantifying Human-Nature Interactions
Team: John Darling (PI) (mentor), Amy J. Davis (ORISE Post-Doctoral Fellow), Anne Neale, Megan Mehaffey (NERL)
Summary: Big data analytics represents an unparalleled opportunity to overcome the financial and structural limitations inherent to traditional data collection methods and extract meaningful inferences about patterns of human behavior across large spatial scales. Data on how humans utilize green spaces and interact with nature are collected using costly surveys, and thus are limited in geographic scope and/ or to a limited set of predefined recreational activities, or are merely summarized as the number of visitations to parks and other natural areas. We have identified a methodological framework utilizing big data analytics aimed at furthering our understanding of human-nature interactions and their relationships with human health outcomes. Overall, this framework entails mining social media data to derive metrics of human-nature interactions and examining their relationships with community health indicators such as rates of substance abuse, cancer, diabetes, obesity and child health for 28 cities across the U.S., as provided by the Big Cities Health Coalition. Our methodology represents a novel opportunity to move beyond EPA’s focus on chemical stressors and to investigate the effects of non-traditional stressors or benefits on human health while avoiding the expense of standard approaches to data collection.
Title: Bittersweet: A neuroendocrine AOP linking environmental stressors to glucose homeostasis
Team: Samantha J. Snow (PI) (R-Authority Post-Doctoral Fellow), WanYun Cheng, Rory Conolly, Mehdi Hazari, Urmila P. Kodavanti (mentor) (NHEERL)
Summary: Most high-throughput technologies allow a snapshot picture of biological processes, but not a multidimensional view of in-life, real-time biomolecular changes as environmental stressors are encountered. Newly developed technology, such as glucose telemetry implants, provide an opportunity to acquire dynamic temporal data for biomolecules in freely-moving animals, which is critical for support of computational modeling of biological effects of environmental stressors. We propose to utilize new telemetric technology in a novel manner to measure dynamic changes in glucose levels inside the body of a freely-moving animal during and following exposure to an environmental irritant. These real-time data will be critical as a first step in taking our new neuroendocrine stress response adverse outcome pathway to a quantitative level.
Title: Chemical signatures of neurodevelopmental disorders
Team: Tim Shafer (PI), Bill Mundy, Kathleen Wallace (NHEERL); Matthew Henderson, (NERL)
Summary: Protecting children’s health is a high priority for the Agency, and mounting evidence links environmental exposures to the prevalence of learning disabilities and neurological disorders. Recently, we established a “brain-on-a-chip” assay for rapid in vitro detection of chemicals that could affect brain development, based on measuring the development of functionally connected neurons, referred to as a neural network. Chemicals that effect neural network formation could alter brain development, but currently cannot be equated to specific children’s health outcomes. To move beyond simply detecting potential neurotoxic chemicals and begin to build predictive models for chemical-induced neurological disease, we propose to combine the rich functional information gained through monitoring neural network development in the brain-on-a-chip assay with assessment of metabolic and genomic changes in the same assay. Characterization of these transcriptomic and metabolomic changes will allow us to determine a molecular “signature” which can be compared to signatures observed in children with neurological diseases.
Title: Degradation of cyanotoxins in drinking water using chitosan-derived nitrogen-enriched carbon dots
Team: Rajender S. Varma (PI) (mentor), Mallikarjuna N. Nadagouda, Sanny Verma (ORISE Post-Doctoral Fellow) (NRMRL)
Summary: Cyanotoxins are produced by cyanobacteria especially in nutrient-rich waters. At certain concentrations, cyanotoxins are hazardous and can result in poisoning of animals and human beings. In this project, we plan to use chitosan-derived nitrogen- enriched carbon dots to degrade and remove these cyanotoxins from the drinking water. Chitosan will be converted into nitrogen-doped carbon dots which will absorb the visible light energy and transfer into the surroundings to degrade cyanotoxins.
Title: Go with the flow: Mechanotransduction during cardiovascular development
Team: Kyle Grode (Co-PI) and David Belair (Co-PI) (R-Authority Post-Doctoral Fellows), Sid Hunter (mentor) (NHEERL); Tom Knudsen (NCCT)
Summary: Mechanical forces are essential to the development and maintenance of virtually all tissues and organs. Consequently, defects in mechanotransduction – the mechanism by which cells convert mechanical signals into biochemical responses – have been implicated in a wide range of congenital and adult-onset diseases. Chemical disruption of either mechanical stimuli or the ability of cells to sense their physical surroundings thus represent potential mechanisms leading to profound developmental and organ-specific toxicity. We propose to pioneer the use of cutting-edge technology to investigate the mechanical basis of chemical susceptibility during cardiovascular development – a critical life stage in which the frictional force of fluid flow controls blood vessel and early heart formation.
Title: Integrating ‘omics using epidemiology: A new paradigm in risk assessment
Team: Radhika Dhingra (PI) (R-authority Post-Doctoral Fellow), Ana Rappold (Co-Mentor), David Diaz-Sanchez (Co-Mentor) (NHEERL)
Summary: The potential to use these High Dimensional Biology or ’omics approaches to identify susceptible populations and individuals is apparent. However, trying to identify an individual’s susceptibility using, for example, genomics alone is like trying to diagnose the health of a patient by only listening to their heart. Attempts at integrating ‘omics techniques have been hampered by the reliance on purely statistical techniques. Here we propose to take a radical new approach by borrowing techniques from the related but distinct epidemiology discipline. We propose employing cutting-edge epidemiological tools to integrate distinct ‘omics datasets. Success has the potential to transform risk assessment by providing a quantitative measure of risk based on directly applicable biology.
Title: Online Air Quality Mapping of Real-Time Traffic Emissions
Team: Tim Barzyk (PI), Brian Eder, Vlad Isakov, Rohit Mathur, Betsy Smith, Rob Gilliam (NERL); Sue Kimbrough (NRMRL)
Summary: The challenge is to produce real-time air quality estimates of emissions and dispersion from major pollution sources such as roadways. Real-time data on traffic and meteorology produce the most precise estimates of emissions for local-scale and regional models, and of dispersion for acute and chronic exposures and predictive alerts, especially for vulnerable populations. This research will transform the specificity and precision of air quality impacts, targeting real-time, real-world emissions and exposures at extremely fine resolutions that have never been seen before, surpassing even dense measurement networks in terms of spatial and temporal coverage.
Title: Red Blood Cells: Trash Heap or Harbingers of Environmental Stress?
Team: Leslie Thompson (PI) (R-Authority Post-Doctoral Fellow), Aimen Farraj (mentor), Wayne Cascio, Mehdi Hazari, Stephanie Padilla, and Dan Villeneuve (NHEERL)
Summary: Conventional clinical and toxicological approaches are costly and low throughput, while easier, more rapid screening approaches that definitively link air pollution exposure to altered cardiovascular function remain elusive. Red blood cells (RBCs) are the most abundant cell type in humans, are paramount to survival (i.e. oxygen transport), and with 100%of RBCs passing through the lungs, the site of air pollution exposure, may serve as dynamic sensors and first-responders to environmental stress. However, RBCs are routinely discarded in air pollution studies in favor of targets of much lower abundance based on the misunderstanding that RBCs are only benign oxygen delivery agents. In a collaborative effort, NHEERL scientists will evaluate RBC membrane deformability, oxidative stress, and signaling molecule release for suitability for rapid screening and use as biological initiating events/biomarkers of cardiovascular responses to environmental stress in an adverse outcome pathway (AOP) framework. This project may also foster integration of human health and ecotoxicology risk assessment efforts given that RBCs are found in nearly all vertebrates (including fish), presenting a common target for investigation of conserved stress responses across multiple species.
Title: Wearable Air Quality Sensors and Health
Team: Ana Rappold (PI) Bryan Hubbell, (ORD); Stephanie DeFlorio-Barker, Kristen Rappazzo, Lucas Neas, and Wayne Cascio (NHEERL)
Summary: Wearable air quality sensors (WAQS) have emerged as a means to provide real-time readings of air quality (AQ), thus empowering the wearer to adopt behavior to mitigate their personal exposure. We propose to investigate the utility of WAQS technology to influence human behavior by providing exposure information at an individual level.
Stage 2 (Awarded August 2017)
Big Data and Real Time Air Quality Mapping for State and Local Planning
Team: Timothy M. Barzyk (PI), Vlad Isakov (Co-PI), Betsy Smith, Rob Gilliam, Rohit Mathur (NERL); Sue Kimbrough (NRMRL)
A Novel High Throughput Toxicity Screening System Using Volatilomics
Team: Michael Madden (PI) (NHEERL); Michelle Angrish (NCEA); Ariel Wallace, Joachim Pleil (NERL)
Chemical Signatures of Neurodevelopmental Disorders
Team: Tim Shafer (PI), Kathleen Wallace, Theresa Freudenrich, Brian Chorley, Susan Hester (NHEERL); Matthew Henderson (NERL)
Stage 3 (Awarded August 2017)
Building a Network to Measure the Totality of Chemical Exposures
Team: Jon Sobus (PI), Elin Ulrich, Seth Newton, Kristin Isaacs, Katherine Phillips, Mark Strynar, Carry Croghan, Matthew Scott Clifton (NERL); Antony Williams, Ann Richard, Chris Grulke, John Wambaugh (NCCT)
Water Utility Lime Sludge Reuse in Power Utilities
Team: Craig Patterson (PI), Regan Murray (NRMRL)