Seminars

Widespread PFAS contamination has forced a fundamental shift in environmental protection strategies. This talk will explore North Carolina’s experience with PFAS following the discovery of high levels of GenX and other PFAS compounds in the Cape Fear River, along with a discussion of the importance of science-based standards, cross-sector partnerships and technology to better public health outcomes in an increasingly complex landscape.

Environmental exposures, including chemical contaminants and heat stress, pose a major risk to kidney health, particularly contributing to an emerging epidemic of chronic kidney disease in tropical farming communities. I will discuss our community-engaged, bench-to-bedside approach investigating how these exposures contribute to disease onset and progression in impacted communities and will highlight the use of zebrafish (Danio rerio) as a mechanistic model and a screening tool to inform adult and pediatric cohort studies.

Metabolic health issues are rising worldwide and concurrently humans are exposed to various chemicals from as early as gestation. Epidemiological studies have linked the prevalence of metabolic diseases to exposure to endocrine disrupting chemicals (EDCs). To investigate the disruption of metabolic pathways by EDC mixtures from common exposure sources, I used a combination of in vitro and in vivo models. I have confirmed the ability of several chemicals to disrupt PPARγ signalling and increase lipid accumulation in vivo. Furthermore, I confirmed that these chemicals disrupt metabolic health in developmentally exposed zebrafish, through changes in metabolic activity, swimming behaviour and gene expression. Lastly, I observed an increased prevalence of fatty liver in zebrafish developmentally exposed to PFAS. My short-term goal is to understand the molecular perturbations caused by PFAS that lead to hepatic steatosis by studying perturbations in signalling and mitochondrial function in hepatocytes. My long-term goal is to become an independent researcher investigating the onset of metabolic dysfunction-associated steatotic liver disease (MASLD) and co-occurring cardiovascular diseases caused by environmental toxicants.

This program represents an important initiative to provide necessary care to the most vulnerable communities a6ected by a series of environmental and social determinants of health after hurricanes, earthquakes and the covid pandemic.

Autoimmune diseases include more than 140 disorders characterized by abnormal immune system activity, where inflammation is driven by autoantibodies and self-reactive T cells. The prevalence of autoimmune diseases is on the rise, affecting up to 25 million people in the US. Our lab’s objective is to uncover how exposure to environmental contaminants trigger autoimmunity, with the aim of identifying intervention strategies to restore normal immune function.

Matt Bozigar is an environmental epidemiologist with a multidisciplinary background. He studies multiple adverse environmental exposures (e.g., noise, air pollution, aeroallergens, radon) and health outcomes (e.g., asthma, cancer, cardiometabolic risk factors and diseases). Matt views environmental epidemiology through a geographical lens that emphasizes “place” and how it affects the health of populations.

Derived from her extensive studies of xenobiotic nuclear receptors (NRs), Shujuan Chen's research interests have expanded to include nuclear receptor corepressor (NCoR1) and its physiological and pharmacological functions. Implementing mouse genetics and in vitro 3-D organoid culture, she has demonstrated the central role of NCoR1 in intestinal health and inflammatory bowel disease (IBD). These findings led her to the field of intestinal innate immunity, including studies of intestinal stem cell proliferation and differentiation, secretory cells, antimicrobial peptides, gut microbiome, and the interactions of host and intestinal bacteria. Her other research focus is investigating the impact of environmental toxicants on neonatal development, brain toxicity, hepatocellular carcinoma (HCC), and colorectal cancer (CRC); these studies include the environmental toxicants arsenic, cadmium, triclosan, benzopyrene, and some polyaromatic hydrocarbons (PAHs).

Dr. Emily Ho's research interests are in the area of antioxidants and gene expression and dietary chemoprevention strategies. She is the leader of the EHSC Translational Research Support Core, Directory of the Linus Pauling Institute, and Co-Director of the Center for Healthy Aging Research.

Dr. Diana Rohlman studies the role of environmental health literacy in helping communities better frame and respond to environmental health hazards. She is the leader of the EHSC Community Engagement Core and co-leader of the SRC Community Engagment Core, where she is working to bring researchers and impacted communities together on collaborative projects.

NPIC provides objective, science-based information about pesticides and pesticide-related topics to enable people to make informed decisions about pesticides and their use. NPIC is a cooperative agreement between Oregon State University and the U.S. Environmental Protection Agency. 

Buildings have far-reaching impacts on public health and well-being. Buildings are the largest energy use sector and they have had the least improvement in their energy efficiency compared to other sectors. Therefore, they are responsible for the majority of the emissions, and at the same time, they also present a great opportunity in reducing energy consumption and emissions by making buildings more energy efficient. Buildings are also where people spend about 90% of their lifetime.
The indoor environment affects people’s health and well-being, performance, and productivity. Therefore, it is critical to have buildings that are high-performing and also healthy and resilient.
In this presentation, Dr. Salimifard will share her academic career journey as well as some of her research projects focusing on the connections between indoor air quality, building energy performance, emissions footprint of buildings and their climate impacts, and public health impacts of buildings, and how to leverage building science to design and operate buildings that are sustainable, healthy, and resilient.

The complexity of the thyroid hormone signaling pathways present a myriad of targets for interference by environmental chemicals.  Because thyroid hormones are essential for normal brain development, there is a significant public health need to protect the developing brain of the fetus, newborn, and young child from thyroid system-disrupting chemicals (TSDC). This concern has led to the development of a suite of in vitro-based methodologies (NAMs) targeting specific sites within the thyroid system where chemicals may act.  Currently, regulatory decisions for TSDC are largely based on alterations in circulating levels of thyroid hormone in rodent studies, but translation from NAM outputs to serum hormones is lacking. So too is our understanding of the relationships between concentrations of TH in serum, target tissues, and the downstream effects on brain development. This presentation will provide an overview of current approaches to identify and characterize TSDCs for informed regulatory decision making. It will focus ongoing research efforts to unravel how TSDC interfere with thyroid signaling at the molecular, structural, and functional level using a case study with the drinking water contaminant perchlorate.  Does not reflect US EPA policy. 

Polycyclic aromatic hydrocarbons (PAHs) are a class of environmental contaminants associated with carcinogenic, mutagenic, and teratogenic health effects. Bioremediation is an attractive option for PAH remediation due to its low cost and low energy requirements, however bioremediation can lead to the formation of toxic PAH transformation products. In pursuit of novel bioremediation strategies, exploratory work was conducted with the pure bacterial culture Rhodococcus rhodochrous ATCC 21198 and monoaromatic hydrocarbons (BTEX), which provided the foundation for PAH bioremediation strategies. PAH bioremediation studies required monitoring methods that could provide results in real-time, which traditional analytical techniques could not provide. Thus, a method for rapid analysis of PAHs in aqueous samples was developed using excitation-emission matrix (EEM) fluorescent spectroscopy and parallel factor analysis (PARAFAC) that eliminated the need for extensive sample preparation and separation techniques before analysis. This work also inspired additional method development endeavors for a more complex biological system: embryonic zebrafish. Following the foundational microbial work and method development research phases, our work in PAH remediation technologies has commenced and expanded to include surfactants and immobilized cells for combined remediation strategies. Metrics for remediation success included reduction of parent PAH concentrations, accumulation of PAH metabolites, and overall toxicity of the treated material. Outcomes of this research has demonstrated the utility of 21198 as a candidate for aromatic hydrocarbon bioremediation, provided a new tool for monitoring aqueous PAH concentrations in biological systems, and highlighted the importance of toxicity considerations in PAH remediation efforts. 

Total petroleum hydrocarbon (TPH) contamination is present at numerous Superfund sites across the nation. Hydrocarbon products are complex mixtures containing perhaps hundreds of hydrocarbon compounds and compositions vary among different products. Once released, the composition of a hydrocarbon product will change due to differential fate and transport of its components. To estimate the human health hazards and risk associated with TPH exposure at Superfund sites, a fraction-based approach was taken in the Provisional Peer Reviewed Toxicity Value (PPRTV) assessment of these complex mixtures. The TPH mixture was divided into 6 subfractions, defined based on structural attributes and further categorized by carbon and equivalent carbon ranges. The health risk of each fraction can be estimated using a variety mixture assessment approaches, including the indicator chemical method, surrogate mixture method, hazard index method, or relative potency factor method, with method selection driven by data availability. Fraction-specific hazard and risk estimates are then summed using either dose (noncancer) or response (cancer) addition to provide an estimate of mixture hazard or risk. Background on the PPRTV Program, mixture risk assessment methods, and an example calculation will be presented.

Applicants for the Pacific Northwest Center for Translational Environmental Health
Pilot Project Program will be sharing their research ideas in short Ignite Pitches.
This is a chance to learn about the state-of-the-art science, technology, and
stakeholder engagement ideas being pursued by members in the Center and ask questions about their latest
research ideas.

Speakers: Each speaker has 6 minutes to share their ideas followed by 4 minutes for questions.

Molly Kile is an environmental epidemiologist whose research focuses on understanding how exposures to chemicals influence human health. Her expertise is in conducting population-based environmental health studies and often works with communities that are disproportionately impacted by environmental pollutants. She received her doctoral degree from Harvard School of Public Health in 2006 and is currently a Professor at the College of Public Health and Human Sciences at Oregon State University. She is currently the PI on two active NIEHS-funded R01s that are studying the effects of flame retardants on children’s neurocognitive and behavioral growth and private well water stewardship. She is also interim deputy director of the Pacific Northwest Center for Translational Environmental Health Research (P30) and the co-PI of the newly formed ASPIRE Center at OSU (P2C) that is focusing on accelerating the adoption of evidence-based policies, programs, and practices that promote children’s environmental health.

Arsenic exposure is a global public health problem. Arsenic is a multi-organ toxicant and chronic exposure causes multiple chronic diseases including cancer. Skin cancer is the most common cancer caused by arsenic exposure but the mechanism(s) of carcinogenesis remain unclear. This presentation focuses on dysregulation of RNA metabolism in an in vitro model of skin carcinogenesis by chronic low level arsenic exposure. Dysregulated expression of microRNA and mRNAs and alternative mRNA splicing and the intersection with chromosomal instability will be discussed.

The NLRP3 inflammasome has been identified as a key immune sensor for tissue damage. Although NLRP3 inflammasome assembly/activation leads to the production of inflammatory messengers (called cytokines) that alert the host immune system to initiate inflammatory responses, its dysregulation often results in overt diseases due to uncontrolled inflammation. Unfortunately, exposure to a number of environmental toxicants including PFAS have been shown to induce NLRP3 inflammasome activation that in turn initiates an undesirable inflammatory response, thereby causing numerous pathologies. Although stimulating agents have not been demonstrated to directly bind NLRP3, they are able to trigger mitochondrial damage and subsequent release of mitochondrial contents that somehow signal the activation of NLRP3 inflammasome. We seek to identify the mitochondrial ligand responsible for direct NLRP3 activation and probe the molecular determinants of recognition for this interaction.

Chemical risk assessments follow a multistep paradigm that involves identifying hazards associated with exposure to a chemical and developing quantitative dose-response information that, when combined with exposure information, is used to characterize risk and inform risk management decisions. Evaluating human health risk from exposure to mixtures rather than individual chemicals adds another level of complexity to this process. EPA’s Mixtures Guidance defines a chemical mixture as “any combination of two or more chemical substances regardless of source or of spatial or temporal proximity” and presents approaches for assessing the risks from chemical mixtures that depend on the nature of the available data. Information on the specific whole mixture of concern or a similar mixture are preferred, but frequently such data are not available. Component approaches are a third, commonly used option that allows for utilization of data on the individual components of a mixture in a process that is informed by what is known about the similarities of the mixture components. Further, a fraction-based approach consistent with EPA’s Mixtures Guidance addresses concerns regarding the effects of weathering and defines petroleum hydrocarbon fractions on the basis of expected transport in the environment and analytical methods used to identify and quantify such environmental contaminants. For petroleum hydrocarbon fractions, the fraction-based approach has been utilized to generate Provisional Peer-Reviewed Toxicity Values (PPRTVs), which are primarily derived for use by EPA’s Superfund Program. This presentation will provide an overview of approaches for estimating health risk from chemical mixtures with greater attention being given to hydrocarbon mixtures. Examples to be discussed in greater detail include estimating cancer risks from exposure to PAH mixtures using a component approach and use of a fraction approach for derivation of PPRTVs for complex mixtures of aliphatic and aromatic hydrocarbons. The views expressed in this presentation are those of the author and do not necessarily represent the views or the policies of the U.S. Environmental Protection Agency.

Exposure of babies to chemicals can increase the risk of disease later in life. This presentation will discuss factors that regulate the extent to which chemicals reach the baby through the placenta. Our research team is particularly interested in fungal-derived estrogenic toxins, known as mycoestrogens, that are present in the food supply and implicated in reproductive and developmental toxicities. 

Applications for the Strategic Initiative Awards:

• Dr. Diana Rohlman (OSU) “Wildfire Smoke and Infant Health”
• Dr. Sarah Rothenberg (OSU) “Reducing Methylmercury Exposure through Fish Consumption in Lane County, Oregon”
• Dr. Manuel Garcia-Jaramillo (OSU) “Identification and Evaluation of Toxic Contaminant Mixtures in Surface Water from the Portland Harbor Superfund Site Using Effect-Directed Analysis Coupled to Non-target High-Resolution Mass Spectrometry”

Applications for the Vanguard Awards:

• Dr. Veronica Irvin (OSU) “Development of a treatment decision aid for home environmental contaminants using a mobile approach”
• Dr. Siva Kolluri (OSU) “p27/Kip1 cell cycle inhibitor as an unexpected regulator of PAH toxicity”
• Dr. Lew Semprini (OSU) “Cometabolic Treatment of 1,2,3-Trichloropropane in Hydrogel Beads and the Evaluation of Toxicity Reduction Using Embryonic Zebrafish Assays”
• Dr. Karen Guillemin (UO) “Modulation of tissue iron by microbiota, inflammation, and environmental exposures”
• Dr. Susan Tilton (OSU) “Development of a 3D respiratory co-culture model for assessing toxicity to chemicals from wildfire smoke”

Immense agrochemical inputs, including pesticides and nutrients, are required for crop production and their use is incredibly inefficient. When considered at the global scale, these inefficiencies have tremendous economic and environmental consequences caused by emissions to the atmosphere (e.g., greenhouse gases) and surrounding water bodies (e.g., eutrophication). There are also massive losses of embodied resources and emissions when agrochemicals do not reach their target. As such, there is an opportunity for innovative solutions to have a big impact on an industry that is critical to the wellbeing of the global population. Yet, choices we make about the raw materials we use and how we design new technologies to increase performance have upstream (e.g., embodied resources) and downstream (e.g., emissions) implications. A combined approach that involves design decisions at the molecular level with systems-level analyses is necessary to preclude shifting burdens to other life cycle stages and to uncover high impact contributors across the life cycle. In this talk, I will discuss research from my group that aims at defining and addressing agrochemical use inefficiencies in crop production, including (i) evaluating tradeoffs of proposed nanotechnology solutions, (ii) sustainably designing carriers for delivering agrochemicals more efficiently to roots, and (iii) modeling nitrate transport and uptake in soil.   

My lab studies a cell-to-cell communication system that the body uses to maintain homeostasis. When environmental exposures disrupt homeostatic communication patterns, we seek to detect those shifts by “listening in” to the communications mediated by circulating extracellular vesicles (EVs). EVs are tiny (<1 µm) membrane-bound vesicles, which encompass exosomes, microvesicles, microparticles and other types of vesicles, released into the bloodstream by human cells and can be easily studied in blood samples. EVs contain cargo, such as non-coding RNAs, that can act on the recipient cell to modify it. My lab found overall patterns, based on the concentrations of EVs and their cargo, before disease develops. We also determined that EV-based communication is highly sensitive to environmental exposures. However, human data on EVs as a potential mediator of environmental toxicity are limited. I will present evidence from human environmental studies indicating that EV encapsulated miRNAs may mediate effects caused by toxic exposures. In these investigations, we have shown that exposures, including air pollution, BPA and other chemicals, strongly modify the EV-miRNA profiles. I will present data demonstrating that altered EV-miRNA profiles are associated with disease. Based on current evidence, I will propose possible models for the interplay between toxicants and EVs in human health and disease.

The field of toxicology has long suggested that host microbiota could influence the disposition and toxicity of environmental chemicals. Early correlative studies of heavy metal exposure identified the microbiota as contributing to host toxicity. However, technological limitations necessary for cataloging the microbiota community structure and for characterizing their metabolic capabilities have hitherto hindered progress in this area. Technological advances including sequence-based identification and functional characterization via mass spectrometry-based metabolite profiling have begun to shed light on how microbes influence and/or impact toxicity outcomes. Data will be presented to highlight key aspects of gut microbiota-host interaction and how environmental chemicals (dioxins, furans, polychlorinated biphenyls) can impact this important connection.

Adult and prenatal exposures to the pesticide DDT and its metabolite DDE have been associated with risk of obesity in subsequent generations of people, mice and rats in numerous studies.  Our research indicates that these obesogenic effects are caused by impaired metabolism. We have observed that prenatal exposure to DDT or DDE impairs body heat production in mice from their first week of life to 9 months of age. Indeed, metabolic reductions in thermogenesis, the production of body heat, are associated not just with DDT and DDE exposures, but also with numerous pharmaceuticals and genes that are known to cause obesity. Epigenome studies in both mice and humans with DDT and DDE exposures have revealed extensive changes in DNA methylation enriching the thermogenesis pathway, including changes in DNA methylation of upstream signaling and substrate regulation pathways. Defects in the thermogenic function but not the structure of mouse brown adipose tissue and cultured brown adipocytes have observed. Additionally, prenatal DDT reduces the innervation of mouse brown adipose tissue, and the upstream synaptic connectivity is reduced by either DDT or DDE exposure prenatally. This body of research evidence indicates that both DDT and DDE act as obesogens by targeting both brown adipose and the sympathetic nervous system to impair thermogenesis.

A growing body of evidence supports a role for environmental contaminants, such as air pollutants and toxic metals, in the development and progression of cardiometabolic disease in adults. However, relatively little is known about the influence of these exposures on cardiovascular and metabolic disease risk during vulnerable lifestages, such as childhood, adolescence and pregnancy. For example, pregnancy may act as a window of susceptibility to environmental exposures, but relatively few studies have explored the effects of environmental contaminants on maternal prenatal and postpartum health. Among children, in utero and early life exposures may impact subclinical markers of cardiovascular dysfunction, with potential implications for cardiovascular health trajectories. As such, these lifestages may represent critical periods for intervention, as exposures during these times may exacerbate the risk of long-term cardiometabolic health effects. In this seminar, Dr. Farzan will discuss emerging research in this area, with examples from her work investigating the role of prenatal environmental exposures and psychosocial stressors on maternal perinatal cardiometabolic health, as well as the role of metals and air pollutants on subclinical indicators of cardiovascular disease risk from childhood to young adulthood. 

Fred Tyson is a Program Director in the Genes, Environment and Health Branch of the Division of Extramural Research and Training (DERT) at the National Institute of Environmental Sciences. He received his PhD in cell biology and developmental genetics from Rutgers University.   Postdoctoral training in molecular genetics was obtained at Sloan-Kettering followed by additional training in molecular oncology at Duke.  Tyson served as a Senior Staff Fellow at NIEHS in the Laboratory of Molecular Toxicology and as a Senior Scientist at the Saccamanno Cancer Research Institute in Grand Junction, CO. As an NIEHS program officer, Tyson has developed a research portfolio that employs multi-disciplinary approaches to address environmental health science issues.  He has supported diverse research programs in environmental justice, health disparities, genomics, epigenomics, epitranscriptomics and marine toxicology. His current portfolio responsibilities include oversight of grants and programs addressing lung cancer, electronic nicotine delivery systems, oceans and human health as well as programs that address how environmental exposures may perturb epigenomic and epitranscriptomic processes. He has worked with trans-NIH programs as well as leading components of Common Fund supported initiatives as well as working across agencies such as the NSF, FDA, CDC and NOAA to advance environmental health science research priorities. 

Toxicology testing has traditionally relied on rudimentary single endpoint outcomes. With the advent of single cell technologies, the biological unit of the cell can be interrogated at the mechanistic level. With recent advances in single cell transcriptomics, an unprecedented level of detail is now revealed on a per cell basis. These technologies now allow the assessment of population heterogeneity and the effect of chemical perturbation on cellular heterogeneity. Here Dr. Karmaus will discuss an example of applying single cell transcriptomics for evaluating the attenuation of T cell activation by atrazine. 

Peer Karmaus is a Staff Scientist at the National Institute for Environmental Health Sciences and an Adjunct Assistant Professor at Michigan State University. His research focuses on how metabolism in innate and adaptive immune cells dictate cell fate and function.

The COVID-19 pandemic has resulted in 153 million infections and 3.2 million deaths as of May 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as potentially antigenically distinct SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we carried out a collaborative effort with Dr. Michel Norris and Dr. Stephanie Karst to perform genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. We identified multiple genes and functional pathways that have been previously reported to promote human coronavirus replication as well as novel genes and pathways. Of note, host factors involved in cell cycle regulation were enriched in our screens as were several key components of the programmed mRNA decay pathway. We identified novel candidate antiviral compounds targeting a number of factors revealed by our screens. Our studies substantiate and expand the growing body of literature focused on understanding key human coronavirus-host cell interactions and exploit that knowledge for rational antiviral drug development. 

Per- and Polyfluoroalkyl Substances (PFAS) are a class of global toxicants that are resistant to environmental degradation. Exposure to perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, dampens adaptive immune responses in children. However, it is not known whether PFOS exposure affects the development and function of microglia, the resident innate immune cells in the brain. Using a single cell image analysis pipeline, we found that PFOS exposure produced a rounded, activated microglia morphology in developing zebrafish. PFOS-exposed embryos exhibited a heightened microglial response to brain injury. The exacerbated responses were not due to changes in inflammatory cytokine signaling or an increase in cell death; therefore, we examined other factors in the microenvironment that may modulate microglial development and behavior. Using the photoconvertible calcium indicator CaMPARI, we observed increased neural activity following PFOS exposure. The observed increase may reflect aberrant connectivity associated with the failure of microglia to refine neural networks. Alternatively, the increase in neuronal firing may drive the observed activated microglial phenotypes and alter microglial response to injury. Using optogenetics, we were able to induce a ramified, less activated state in microglia and rescue the exacerbated microglial response to brain injury. We are currently conducting experiments to determine if neural silencing is sufficient to rescue the altered microglial morphology in PFOS-exposed embryos and the microglial response to brain injury. 

Identifying and preventing environmental causes of disease requires estimating long-term personal exposures. Most environmental exposures do not have valid biomarkers and studies therefore rely on external exposure assessment methods.  Approaches are split broadly into methods for modeling exposures for large populations versus measuring exposures for small populations. New technologies and resulting big data offer tremendous opportunity for unifying these approaches and improving long-term personal exposure prediction at scales needed for population-based research.  In this presentation I will provide examples from ongoing research projects, such as: (1) leveraging existing individual time-activity data from Google Location History to estimate long-term environment exposures; (2) integrating image-based deep learning models to assess environmental exposures; and (3) applying new air pollution sensors to large epidemiological studies. I will make the case that a multi-disciplinary approach is needed to combine these types of technologies to improve personal exposure measures, enhance epidemiological research, and identify new prevention opportunities.