Developmental exposure to organophosphorus pesticide to evaluate airway hyperreactivity Epidemiological studies have linked organophosphorus pesticide (OP) exposure to increased risk of asthma in children and adults, yet preclinical evidence supporting this causal link is limited. Dr. Grodzki’s previous work has shown that the OP chlorpyrifos causes airway hyperreactivity (AHR) at low doses that do not inhibit acetylcholinesterase. However, current understanding of the mechanisms involved in OP-induced AHR is incomplete and the question of whether developmental OP exposure could lead to asthmatic symptoms has not been addressed in preclinical models. Dr. Grodzki is investigating the effects of developmental chlorpyrifos exposures on AHR using physiological measurements of lung function and markers of neurogenic inflammation in animal models.
Ozone and lung remodeling More than 4 in 10 US people live in areas with unhealthy levels of ozone. The San Joaquin Valley (SJV) is a hot spot of high ozone exposures. Four of the top 7 most ozone polluted cities in the US are in the SJV where ozone affects more than 1 million children. Ozone exposure during childhood alters lung growth – even healthy young adults from high ozone environments have decreased lung function – yet the mechanisms are little understood. Much research has focused on ozone exacerbation of asthma. Dr. Van Winkle and her team are trying to develop a better understanding of how early life exposure to ozone alters normal lung development. Specifically, the researchers will measure growth in a specific region of the lung, the alveoli, using an animal model and will also determine how ozone exposure early in life alters the growth of alveoli.
Behavioral and neuroimaging phenotypes following early life pesticide exposure Worldwide, organophosphate pesticides are the most commonly used class of pesticides. Epidemiological studies have linked their use to autism, attention deficit hyperactivity disorder, developmental delay, and other neurodevelopmental disorders. Currently, the impacts of early-life exposure to low doses that are representative of what people and, in particular, pregnant women and children may experience, have not been well-studied. Dr. Silverman’s project is measuring the effects of exposure to chlorpyrifos, a widely used organophosphate, during early life on behavioral endpoints and underlying brain anomalies in a rodent model.
Effects of atrazine on the developing ovary Atrazine, a widely used weed killer is a common contaminant found in drinking water. Atrazine is a member of a family of chemicals called the xenoestrogens that mimic the hormone estrogen and thereby disrupt endocrine function. Another xenoestrogen, bisphenol-A (BPA), causes problems in female reproduction. BPA leads to a “grand-maternal effect” that increases the likelihood of developmental problems in grandchildren. Even subtle defects in processes of female reproduction can lead to miscarriage or chromosomal disorders such as Down Syndrome. Dr. Hunter and his team will investigate whether similar effects in female reproduction and birth outcomes are associated with exposure to atrazine.
Noninvasive imaging of immune responses induced by environmental pollutants Exposure to air pollutants and particulate matter (PM) contribute to an increased risk for cardiovascular and pulmonary health problems resulting from chronic inflammation. Dr. Chris Vogel is using a new method for noninvasive imaging of immune responses, Positron Emission Tomography (PET) and magnetic resonance imaging (MRI). The goal of the project is to identify the specific sites of inflammation following exposure to particulate matter and potentially other types of environmental exposures.
Health effects of airborne particulate matter near the Salton Sea: A Community-based exploratory project in the Imperial Valley, CA. The Salton Sea is a man-made, saline lake, located in southeastern California, in the Imperial and Coachella valleys. As a result of climate change, drought, agricultural practices, rural-urban water transfers, the Salton Sea is a polluted and shrinking lake. Communities are concerned about high rates of asthma and the potential role of the Salton Sea as a source of air pollution, both from hydrogen sulfide from the lake bed, and airborne dust and toxic particulate matter, and other health hazards stemming from the lake’s deteriorating water quality and increasingly exposed banks. For this project, Dr. Pinkerton and his team are investigating how particulate matter (ambient PM2.5 and PM10) might sensitize the immune system to house dust mite (HDM) allergen. In particular, the researchers are interested in understanding the role of inflammation, oxidative stress and other pathways of PM-mediated immunotoxicity in the Imperial Valley. The team is working in collaboration with The Environmental Justice Coalition for Water (EJCW) and Comité Cívico del Valle (CCV), and the communities of of Brawley and Calipatria.
Immune mechanisms of ozone-induced lung inflammation in non-human primates Persistent exposure to air pollution leads to changes in immune function in the respiratory system. These changes can trigger allergic asthma and increase susceptibility to respiratory infections. Exposure to high levels of ozone, a major toxic air pollutant, worsens asthma and COPD symptoms. While the exact mechanisms of ozone induced airway disease are not understood, Dr. Haczku and her team are investigating the role of innate lymphoid cells (ILC), specifically the activation of pulmonary and circulating ILC following ozone exposure and the relationship between ILC counts and the extent of airway hyperresponsiveness (a major feature of asthma).
The UC Davis EHS Center Pilot Projects Program is pleased to announce recipients of the 2017-2018 pilot awards: Developmental exposure to organophosphorus pesticides to evaluate airway hyperreactivity – Principal Investigator: Ana Cristina Grodzki, PhD (Department of Molecular Biosciences) Immune mechanisms of ozone-induced lung inflammation in non-human primates – Principal Investigator: Angela Haczku, MD, PhD (Department of Internal Medicine: Pulmonary and Critical Care Medicine) Effects of atrazine on the developing ovary – Principal Investigator: Neil Hunter, PhD (Department of Microbiology & Molecular Genetics) Public health and the intersection of water and air quality in the Salton Sea – Principal Investigator: Kent Pinkerton, PhD (Department of Pediatrics) Cognitive and behavioral and neuroanatomical phenotypes following early life pesticide exposure – Principal Investigator: Jill Silverman, PhD (Department of Psychiatry & Behavioral Sciences) Ozone and lung remodeling – Principal Investigator: Laura VanWinkle, PhD (Department of Anatomy, Physiology and Cell Biology) Noninvasive imaging of immune responses induced by environmental pollutants – Principal Investigator: Christoph Vogel, PhD (Department of Environmental Toxicology)