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Amazon Prime for Inflammation - NLRP3 Inflammasome Activation Mechanism
Department of Molecular Biology and Biochemistry, The University of California Irvine
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.
Ohio State University
SBIR/STTR Opportunities Workshop
|11:00:00 AM: Introduction||Robyn Tanguay|
|11:05:00 AM: Basics of NIEHS SBIR and STTR programs NIEHS|
|ES priority areas and success stories|
|Example Programs NIEHS|
|Basic Program Requirements|
|Company Example #1 (OSU Faculty member)||Steven O’Connell|
|Company Example #2||Roarke Horstmeyer|
|(Company working with OSU Faculty member)||Ramona Optics|
|How can State of Oregon and OSU help?||Karl Mundorff|
|Panel Discussion and Q/A||All|
Daniel T. Shaughnessy, Ph.D.
Health Scientist Administrator
Steven O'Connell, MS PhD
Corvallis, OR 97330
Lingamanaidu V. Ravichandran, Ph.D.
Health Scientist Administrator
Roarke Horstmeyer, PhD
1000 W. Main St., Ste 2A
Durham, NC 27701
Executive Director of Innovation and Entrepreneurship, Director OSU Advantage
Basic Principles Of Human Health Risk Assessment For Environmental Chemical Mixtures With A Focus On Estimating Risks From Hydrocarbon Mixtures
Center for Public Health and Environmental Assessment
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.
Placental Barrier and Fetal Exposure to Mycoestrogens
Lauren Aleksunes, Pharm.D, Ph.D
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.
2022 PNWC-TEHR Pilot Project Ignite Talks
Applications for the Strategic Initiative Awards:
Applications for the Vanguard Awards:
Rebalancing Agrochemical Cycles: From The Molecular To Systems Level
Leanne Gilbertson, PhD
Associate Professor of Environmental Engineering Fulton C. Noss Faculty Fellow
University of Pittsburgh
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.
Exosomes and extracellular vesicles in environmental toxicology – new approaches to assess the impact of environmental exposures on human health
Andrea Baccarelli, MD PhD
Chair and Professor of Environmental Health Sciences, Director, Precision Environmental Health Laboratory
Director, P30 Center for Environmental Health in Northern Manhattan Columbia University Mailman School of Public Health, New York, NY
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.
Environmental Chemical Impact on the Host-Microbiome Interaction
Andrew D. Patterson, PhD
Pennsylvania State University
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.
The Silent Spring of Obesogens: Translational Mechanisms of Obesity Caused by DDT Exposure Across Lifetimes
Michele A. La Merrill, PhD MPH
Associate Professor of Department of Environmental Toxicology
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.