Microscope

Our Pilot Projects Program is one of the main ways we fund environmental health research.

Exposure to near roadway traffic related air pollution (TRAP), inflammation and diabetes onset in the UCD-T2DM rat model of type-2 diabetes

The problem: Millions of residents in the United States live in areas with high levels of traffic related air pollution (TRAP) containing ultrafine particles. People living in California’s Central Valley are exposed to high levels of TRAP which has significant adverse health effects, contributing to lung and heart disease and is associated with Alzheimer’s and type-2 diabetes (T2DM).

T2DM is a serious disease affecting over 30 million people in the United States. The annual costs of T2DM exceed $250 billion and the prevalence of T2DM continues to increase. Diabetes is associated with devastating complications, including heart disease, blindness and kidney failure.

The project: For this project, we will study TRAP exposure in the UCD-T2DM rat model we have developed and characterized in over 24 published studies. Diabetes in the UCD-T2DM rat model is more similar to T2DM in humans than other available rodent models.

We will determine whether UCD-T2DM rats exposed to TRAP for two months exhibit increased inflammation, not only in lung tissue, but also in other tissues with important roles in T2DM, including liver, fat tissue, muscle and brain. We will also follow and compare groups of UCD-T2DM rats exposed to TRAP or control animals (those exposed to clean air) for up to eight months to test whether animals exposed to TRAP develop diabetes more rapidly.

The results of these experiments will provide important new information on the relationship of TRAP to the increasing incidence of T2DM in exposed populations, mechanisms involved in the effects of TRAP and potential interventions to prevent the effects of TRAP on T2DM and its complications. 

Cellular mechanisms of wildfire smoke toxicity

  • Principal investigator: Lisa Miller (lmiller@ucdavis.edu), California National Primate Research Center

The problem: Despite becoming a public health concern, the lasting impacts of acute wildfire smoke inhalation on the development of chronic disease are unknown, particularly in susceptible populations.

The project: Our proposal will identify biomarkers of cellular injury that can be readily detected in peripheral blood and investigate the mechanisms by which inhaled toxicants released from wood combustion can mediate cellular injury in the respiratory tract.

We propose that inhalation of particulate matter less than 2.5 microns in diameter (PM2.5) derived from wildfires can elicit a persistent pathological response by promoting endoplasmic reticulum stress in the airway epithelium from the gas exchange regions of the lung. Our proposed research is supported by preliminary data obtained from infant rhesus monkeys that were exposed to the Northern California Camp Fire in November 2018, as well as findings from a cohort of rhesus monkeys that were exposed as infants to high concentrations of outdoor PM2.5 from Northern California fires in June 2008.

Our aims will (1) measure endoplasmic reticulum stress biomarkers and proteins released by the lung in archived peripheral blood from monkeys exposed to either 2008 or 2018 wildfire smoke PM2.5, (2) measure endoplasmic reticulum stress biomarkers and proteins released by the lung in peripheral blood from human subjects exposed to 2018 wildfire smoke PM2.5, and (3) experimentally assess the effect of wood smoke PM2.5 on parameters of endoplasmic reticulum stress in monkey lung epithelial cell cultures and stem cell-derived human lung epithelial cell cultures.

Biobank for early toxin identification in wildfire burns

The problem: When wildfires burn, they create toxins in smoke and ash that can be absorbed in human beings. The effects of the wildfire-created toxins in humans are unknown because it is difficult to obtain blood samples during the event.

The project: People who are burned in wildfires have prolonged direct exposure to fire toxins, breathe in fire smoke, and lose of the protective skin barrier. Because they are in direct contact with fire and smoke, get routine blood sampling for their care shortly after injury, and are followed up regularly, people burned in a wildfire can allow us to determine what toxins are absorbed in a wildfire and the long-term effects of those toxins.

The purpose of this application is two-fold: 1. Establish a method of obtaining and storing blood samples (biobank) for people with wildfire burns, and 2. Identify the toxins absorbed in a wildfire (in conjunction with EHSC). We will look for many toxins including cyanide, carbon monoxide, and other chemicals produced by household construction materials. In part 1, we will formalize biobank agreements for burn patient sample storage and handling. We will also compare wildfire burn outcomes with other burn outcomes using our established database. In part 2, we will work with EHSC to pilot a toxin panel for wildfire burns.

Identifying the effects of nitrate exposure on embryonic development

The problem: Water systems in the Central Valley of California experience 75% of the reported nitrate exceedances in the state, and nitrate exposure is correlated with embryonic craniofacial defects. Developing embryos are vulnerable to maternal environmental exposures, therefore, it is crucial to identify the nitrate exposure concentrations and the specific window of susceptibility that causes embryonic defects.

The project: We will study the effects of exposure to nitrates on developing neural crest (NC) stem-like cells and their derivatives in two vertebrate research models, chicken and axolotl, with developmental processes similar to human embryos.

NC cells make craniofacial bone and cartilage, neurons in the sensory, sympathetic and enteric nervous systems, and the outflow tract of the heart. Extrinsic or intrinsic perturbations of NC cell development cause disorders such as cleft lip or palate and heart deficiencies.

The goal of our pilot study is to identify specific dose-response and stage-specific exposure phenotypes. We will determine the molecular effects of nitrate exposure on NC cell development and differentiation, and the results from these studies will be utilized as preliminary data for a future NIEHS R01 application.

We intend to use this research as a baseline for future studies on the developmental outcomes of combinatorial exposures to nitrate and other toxins found in Central Valley water. These studies will be performed in combination with community educational outreach to reduce the potential for nitraterelated NC-specific birth defects.

Wildfire Smoke Toxicity from the Wildland-Urban Interface

The problem: Over the last three years, California has experienced increasing incidents and severity of wildfires and an unprecedented invasion of these wildfires into populated areas. Residents of the affected communities and emergency responders have inhaled this smoke for weeks at a time. In addition, the smoke has blown into highly populated areas such as the San Francisco Bay Area and Los Angeles potentially affecting the health of millions of people. During these wildfire events the atmospheric inversion trapped the smoke close to the ground, limiting dilution and increasing exposure concentrations. Members of the UC Davis Environmental Health Science Center (EHSC) have been conducting epidemiological studies to understand the health effects of smoke from these wildfires on affected populations. EHSC scientists have also been collecting the particulate matter (PM) in this smoke for subsequent characterization. But the use of this PM for toxicological studies is problematic.

The project: To complement the epidemiological studies already being conducted by EHSC investigators, we propose building an EHSC core facility that will enable toxicologists to model emissions from fires at the wildland-urban interface. This core facility will consist of a burner that enables temperature control and air flow control to model flaming and smoldering conditions common during and after wildfires. The smoke generator and exposure system will enable UC Davis toxicologists to pursue NIEHS funding to study the wide range of potential health effects of inhaled smoke from fires at the wildland-urban interface.

Contact

If you'd like more information about a particular project, please contact Ruth Williams (ruwilliams@ucdavis.edu) for details.

Tags

Pilot award Lisa Miller Anthony Wexler Keith Bein Tina Palmieri Peter Havel Laura Van Winkle Nam Tran Crystal Rodgers