Qi Zhang, PhD – Department of Environmental Toxicology

  Investigating the links between chemical exposures and toxicological responses for air pollutants using a novel aerosol mass spectrometry method Atmospheric particulate matter (PM) is an important air pollutant associated with cardiovascular disease and other adverse health outcomes. PM can be composed of complex chemical compounds which vary by region and time of year. The connection between the chemical properties of PM and negative health outcomes is still poorly understood. Consequently, there is a critical need for new analytical techniques that can provide rapid, sensitive, and simultaneous measurements of a wide range of toxic species and chemical classes in PM samples. With support from her EHS Center pilot grant, Dr. Zhang is developing a novel technique to enable measurements of a wide range of compounds in both PM and biological samples to investigate the links between PM exposure and biological responses. Through this work, researchers will be able to identify both the sources and key chemical components of PM that contribute to cardiovascular and other diseases. Results from this work will provide much needed information for understanding the health risks associated with PM.

Swee Teh, PhD – Anatomy, Physiology and Cell Biology

Impact of California Drought on Water Quality and Community Health Climate change is likely to have a number of consequences for water quality, for example, increased nitrate levels, toxic algal blooms, concentrations of pollutants (pesticides, pharmaceutical and personal care products), and complex mixtures of these chemicals, that affect human health. Drought will affect groundwater/surface water exchange and pollutants may inadvertently enter well-water resulting in changes in drinking water quality. Consequently, water quality should be screened and monitored regularly. Swee Teh, Director of the UC Davis Aquatic Health Program, received an EHS Center pilot grant to measure chemicals in well and tap water samples from the California Central Valley, an area where large quantities of chemical pesticides and fertilizers are used in agricultural production. Using fish as a model, the researchers are also studying the potential health effects of exposure to the chemicals measured in the water samples, particularly effects on the endocrine system and cancer effects. The team is working closely with citizens groups in the Central Valley to identify locations for sampling.

Ameer Taha, PhD – Department of Food Science and Technology

Streamlining pesticide analysis in human breast milk Pesticides pose a risk to human health, particularly during development, as evidenced by the established correlations between some pesticides and autism spectrum disorder and other developmental anomalies. Although breast milk provides optimum nutrition for infants, it represents a route of exposure to pesticides. Current analytical methods used to probe pesticide levels in human breast milk are expensive and time-consuming due to the large extraction solvent volume requirements (10-40 ml) and the number of steps needed to extract and clean-up samples (5-10 steps). The aim of this proposal is develop a simple method for quantifying pesticides in dried breast milk spot (DBMS) samples using microwave-assisted extraction as a way to reduce solvent volume requirements to 1 ml and bypass clean-up steps. Pesticides will be quantified using a sensitive liquid-chromatography tandem mass spectrometry system. Establishing a rapid, inexpensive DBMS method will enable routine and accurate monitoring of infant pesticide exposure through breastmilk, to better relate exposure risks to developmental outcomes.

Scott Simon, PhD – Department of Biomedical Engineering

Innate immune response to ozone insult and Streptococcus pneumoniae Air pollution is a major health concern, especially for those that live in densely populated urban areas. Breathing in high levels of contaminants increases the likelihood of acquiring serious medical conditions, such as asthma and bacterial pneumonia, and long-term exposure can lead to more serious complications, like chronic obstructive pulmonary disease (COPD). Ozone is a particularly hazardous chemical that is one of the more common air contaminants. Exposure to ozone causes increased inflammation in the lungs and amplifies the susceptibility to bacterial infections. Neutrophils, the primary antibacterial immune cell, play a major role in acute response to ozone exposure. There is a lack of knowledge regarding the sensitivity of neutrophils to ozone insult as well as the effects ozone has on their ability to combat a bacterial infection in the lung. The objective of this study is to gauge the effect of ozone exposure on the innate immune response using a mouse model of infection.

Birgit Puschner, DVM, PhD – Department of Molecular Biosciences

One-shot analysis to determine the concentrations of environmental toxins in low-volume breast milk samples from California women The contribution of the pesticide DDT and its metabolite DDE to breast cancer risk is controversial, where a recent report by the World Health Organization noted the importance of early-life exposure to DDT remains unresolved. We recently demonstrated that prenatal DDT exposure is associated with nearly four-fold higher incidence of breast cancer among adult daughters born at the Oakland Kaiser Permanente hospital in the 1960s. In parallel we exposed mice to DDT while they were in the womb and found they also had nearly four-fold higher mammary tumors. Based on our preliminary research, we suggest that a daughter’s prenatal DDT exposure increases breast cancer risk through altered metabolism that increases tumor growth. The best system to rigorously evaluate this mechanistic hypothesis is cell culture but dosing standard mammary cell lines with DDT would not model prenatal DDT exposure or endocrine carcinogenesis. We seek to establish a plausible mechanism of our striking human and mouse observations by evaluating tumor cells of mice exposed to DDT prenatally. We will characterize the growth and metabolism of these cells and whole mouse tumors.

Charles Lesher, PhD – Department of Earth and Planetary Sciences

Trace metals in dried blood spots: Method development for biomarkers in case-control studies by laser ablation inductively coupled plasma mass spectrometry The major drawback for epidemiologic case-control studies, the most feasible design for rare diseases, is the difficulty in reconstructing accurate exposure levels retrospectively. Newborn dried blood spots (DBS) provide a window into the prenatal period, which is widely considered critical for early development of brain, endocrine, respiratory and other systems, and are available to researchers for all births in California and numerous other states. The ability to characterize metals and minerals using small amounts of DBS will meet an acute need in children’s environmental health. We have previously developed capabilities to quantify Hg in DBS using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS), and further explored the potential of using this analytical method to measure Pb and Zn. Our work highlights the advantages of LA-ICPMS over alternative methods, but further work is required to evaluate and mitigate background contamination and matrix effects. We propose to verify the laser ablation method using matrix-matched DBS standards. These reference standards will be used in an interlaboratory comparison study. Our work will extend and improve the analytical protocols for LA-ICPMS of DBS

Michele LaMerrill – PhD Department of Environmental Toxicology

In vitro model of developmental endocrine disruption The contribution of the pesticide DDT and its metabolite DDE to breast cancer risk is controversial, where a recent report by the World Health Organization noted the importance of early-life exposure to DDT remains unresolved. We recently demonstrated that prenatal DDT exposure is associated with nearly four-fold higher incidence of breast cancer among adult daughters born at the Oakland Kaiser Permanente hospital in the 1960s. In parallel we exposed mice to DDT while they were in the womb and found they also had nearly four-fold higher mammary tumors. Based on our preliminary research, we suggest that a daughter’s prenatal DDT exposure increases breast cancer risk through altered metabolism that increases tumor growth. The best system to rigorously evaluate this mechanistic hypothesis is cell culture but dosing standard mammary cell lines with DDT would not model prenatal DDT exposure or endocrine carcinogenesis. We seek to establish a plausible mechanism of our striking human and mouse observations by evaluating tumor cells of mice exposed to DDT prenatally. We will characterize the growth and metabolism of these cells and whole mouse tumors.

Lillian Cruz-Orengo, PhD – Anatomy, Physiology and Cell Biology

Pioneering a Blood Brain Barrier Disruption Model in Zebrafish Our brain is the most important organ in our body. For such reason the brain and spinal cord, together known as central nervous system (CNS), are guarded by a “fence” called the blood-brain barrier (BBB). The BBB is a protective tissue that prevents most large molecules, toxins, pathogens and cells found in the blood from entering into the brain and spinal cord. When the BBB doesn’t perform well the brain and spinal cord become susceptible to toxic exposure, infection, inflammation, etc causing the CNS to perform poorly. There are many diseases of the CNS that are related to this “breach” of the BBB. However, live animal models to distinguish if toxic compounds, including pesticides, can cause this “breach” and where exactly in the CNS this rupture is happening are missing. It is my purpose to develop a model to observe this process and its location within the brain using zebrafish. Moreover, I want to expose the zebrafish to toxic pesticides that are used here in California, to identify the damage that these pesticides are causing to the BBB and where in the brain this damage is happening. I will identify BBB