Below is a summary of the pilot projects the Environmental Health Sciences Center awarded in 2016.
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 the 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 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 damage by measuring the leakage of neon tracers into the brain and the breakdown of the bonding that keeps together the bricks of the BBB fence. Awareness of this rupture shall motivate us to look for ways to prevent toxic compounds exposure, keeping our brain well-guarded.
Michele LaMerrill, PhD
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.
Charles Lesher, PhD
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 for As, Cd, Mn, Fe, Se, as well as Pb, Zn and Hg. This development work is critical for future comprehensive epidemiologic studies involving newborn dried blood spots.
Birgit Puschner, DVM, PhD
One-shot analysis to determine the concentrations of environmental toxins in low-volume breast milk samples from California women
This research will develop a “one-shot” analysis to determine the concentrations of environmental contaminants in small volume breast milk samples. For proof of principle we will analyze for the presence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methylated analogs.
Although the beneficial aspects of breast feeding are well established, our understanding of how contamination by environmental contaminants in breast milk that could contribute to developmental deficiencies is very limited because current analyses require 10 to 20 ml for extraction. Many human milk banks exist but are not able to provide large milk samples for research studies.
Our research proposal will develop and validate a sensitive analytical method using as little as 1 ml of breast milk. This proof-of-concept strategy will examine a local cohort of breastfeeding women over a 3 to 12 month lactation period to establish a highly selective methodology that will serve as a viable system for identifying environmental toxins in breast milk from large center studies of developmental deficiencies like autism (such as MARBLES) in the future.
PBDEs and analogs serve as realistic surrogates with the goal of expanding the method to other classes of environmental chemicals and metabolites. By assessing these environmental contaminants in breast milk, we will be able to determine inter- and intra-individual variation among women and across lactation and assess a pathway for unintended exposure to infants.
Scott Simon, PhD
Innate immune response to ozone insult and Streptococcus pneumoniae
Air pollution is a major health concern, especially for those who 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.
Ameer Taha, PhD
Food Science and Technology
Streamlining pesticide analysis in human breast milk
Pesticides pose a risk to human health, especially 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 too.
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 to 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.
Swee The, PhD
Anatomy, Physiology and Cell Biology
Impact of California drought on community health – the water quality side
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. Therefore, water quality should be screened and monitored regularly.
We will perform exposure tests using a fish model for assessing carcinogenicity and endocrine disruption on well and tap water samples from the California Central Valley, where contaminants originating from agricultural runoff is causing serious health problems. The advantages of using fish are their relatively short life-cycles and that they live in and ingest the water, shortening response time.
Specific sites will be selected in consultation with the Community Stakeholders’ Advisory Committee. Because chemical detection tells us little regarding the potential toxicity of any individual pollutant or pollutant mixtures that may be present, especially if one or more substances are below the limit of detection, we propose to use a suite of toxicity assays to screen and monitor the potential of drought-related contaminant issues in drinking water using an aquatic fish model for human health.
Qi Zhang, PhD
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 detrimental 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.
The goal of this project is to develop and use 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, we expect to identify both the sources and key chemical components of PM that are potentially responsible for adverse health effects.
Ultimately this work will inform regulatory policy and provide much needed information for risk assessment of air quality with the aim of improving human health.