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

Mechanisms of biological uptake for emerging poly- and perfluoroalkyl substances

• Principal Investigator: Heather Bischel (hbischel@ucdavis.edu), Department of Civil and Environmental Engineering

The problem: Alarming detection of the highly persistent and toxic compounds perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in drinking water was recently linked to the proximity of military bases, where the use of aqueous film forming foams (AFFF) containing these compounds is expected to be their major source. Such legacy compounds have been phased out of commercial production, but complex mixtures of alternative poly- and perfluoroalkyl substances (PFASs) are now used as replacements. Little is known about emerging PFAS toxicity, bioaccumulation, and exposure pathways.

The project: The goal of this work is to rapidly assess the bioaccumulative potential of emerging PFAS in AFFF, and to develop an understanding of the mechanisms of PFAS biouptake via associations with proteins. Select PFAS, including a replacement chemical for PFOA called “GenX”, as well as chemical mixtures of PFASs in AFFF will be exposed to model proteins in synthetic solutions to identify potentially problematic PFAS structures.

Subsequently, an analysis of proteins in serum exposed to AFFF will be conducted to evaluate the potential of irreversible binding of PFAS to proteins. Collaboration with the Green Science Policy Institute throughout the study will facilitate engagement in PFAS policy forums and efficient communication of research results.

Addressing environmental health concerns of community residents of Kettleman City, CA: A community-based approach to examining exposure and assessing community health

• Principal Investigator: Clare Cannon (cebcannon@ucdavis.edu), Department of Human Ecology

The problem: Figure out key linkages between environmental exposure and human health in a disadvantaged, rural community using an innovative participatory process and mixed-method experimental design.

The project: Working with community partners, we aim to conduct an environmental health survey of all households in Kettleman City, CA (N=300) to identify important relationships among sociodemographics, space, health outcomes and environmental risks. These data will be analyzed using cutting-edge strategies, such as geographically weighted regression and structural equation modeling.

Environmental monitoring and biological monitoring will be conducted with select residents (N=10) to collect household water samples to test for mercury, arsenic and chlorpyrifos; ambient air samples of individuals to test for benzene and diesel particles; and blood samples to test for PCBs. Identified experts affiliated with UC Davis EHSC have agreed to analyze environmental and biological samples.

Findings will be shared with the community at regularly scheduled community-run health fairs, and with national audiences through peer reviewed journals (e.g. Environmental Health Perspectives) and national conferences.

Mutation signatures in arsenic-related bladder tumors

• Principal Investigator: Luis Carvajal-Carmona (lgcarvajal@ucdavis.edu), Genome Center

The problem: Exposure to arsenic in drinking water and certain foods cause bladder cancer (BLCA). It is not known however how this carcinogen mutates the DNA to cause this cancer. Understanding how arsenic mutates the DNA is important as such information can be used to prevent and treat BLCA more effectively.

The project: In this study, we propose to study the genome sequence of several tumors from BLCA patients that have been highly exposed to arsenic through drinking water and to compare such genomes with those of tumors from unexposed BLCA patients. Our goal here is to identify mutation patterns that are specific of arsenic-related tumors and potentially important drug targets in these tumors.

Epigenetic mechanisms underlying carcinogenic effects of light pollution and circadian clock disruption 

• Principal Investigator: Joanna Chiu (jcchiu@ucdavis.edu), Department of Entomology and Nematology

The problem: Flipping on a light switch at night is second nature to humans living in modern societies, and few would contemplate the possible health consequences. However, accumulating evidence suggest that artificial light at night (ALAN) may actually be one of the most pervasive environmental health hazards that contribute to a wide range of human diseases, including cancer.

Results from epidemiological studies prompted WHO to designate shift work as a carcinogen. For instance, women who work night shift have been shown to manifest increased breast cancer rates, which cannot be explained solely by genetic factors. The cause of elevated cancer risk in shift workers is attributed to ALAN, which disrupts the circadian clock, an endogenous timer in our body that controls timing of physiological processes and is critical for maintaining health span.

The project: This project will investigate the mechanisms underlying the carcinogenic effects of ALAN by focusing on the deleterious outcome of ALAN on clock-controlled daily modifications in genome structure and function.

We will engage community partners to leverage our results and pave the way to the development of therapeutic strategies, occupational health practices, and insightful city/building planning to reduce risk of cancer and other diseases associated with LAN.

Feasibility study to identify and collect data on environmental risk factors from Hispanic women diagnosed with lung cancer

• Principal Investigator: Rosemary Cress (rdcress@ucdavis.edu), Department of Public Health Sciences

The problem: Risk of lung cancer among never smokers is not well understood and prior studies of this topic have produced confusing results. Added to these challenges is the fact that identifying a large group of lung cancer patients who are never smokers is difficult, particularly because cancer registries do not collect smoking history.

The project: The purpose of this pilot project is to assess the feasibility of using the cancer registry to identify lung cancer patients who are never smokers, and to assess the feasibility of using a telephone interview to identify patients’ exposure to environmental risk factors. We will recruit female Hispanic patients recently diagnosed with adenocarcinoma of the lung.

This work will be used to apply for funding for a larger study to investigate risk factors for lung cancer in nonsmokers, which ultimately should lead to prevention of some lung cancer deaths.

Genome-wide epigenetic analysis of brain and lung resident immune cell response to traffic-related air pollution

• Principal Investigator: Janine LaSalle (jmlasalle@ucdavis.edu), School of Medicine, Department of Medical Microbiology and Immunology

The problem: Epigenetic mechanisms such as DNA methylation act at the interface of genetic and environmental risk factors in the etiology of complex diseases such as autism spectrum disorders (ASD), asthma and cardiovascular disease. Early life exposure to traffic-related air pollution (TRAP) has been consistently implicated as a risk factor for both asthma and ASD, although the mechanisms underlying the long-lasting effects of TRAP exposures are poorly understood.

The project: We isolated microglia from brain and immune cells from bronchoalveolar lavage fluid in the lungs of rats exposed to TRAP. We propose isolating DNA and RNA from these frozen cell samples and perform both whole genome bisulfite sequencing for DNA methylation and RNA-seq for transcriptome.

The overall goal is to perform an unbiased genome-wide analysis of the effects of TRAP on immune cells responses in both brain and lung. Data will be used to formulate new mechanistic hypotheses to be tested in future NIEHS grant applications.

Silicon Wristband Exposome and Autism Pilot (SWEAP)

• Principal Investigator: Rebecca Schmidt (rjschmidt@ucdavis.edu), Department of Public Health Sciences

The problem: Autism is a growing problem world-wide, with as many as 1 in every 68 children affected in the United States. Both environmental and genetic contributions are thought to play a role in autism causation, but little is known about which environmental factors increase risk. Understanding risk factors can facilitate prevention strategies.

The project: We propose to be the first study of genetically susceptible high-risk siblings of children with autism to comprehensively investigate a broad array of prenatal and early child environmental contaminants in relation to autism using a novel, low burden exposome wristband approach. Silicone wristbands can be used as passive sampling tools for measuring personal environmental exposure to over 1,500 compounds including pesticides, air pollutants, contaminants from consumer and personal care products and other industrial compounds.

For this project, we will pilot collection of silicone exposome wristbands worn for one week at multiple time points during pregnancy and early childhood, a critical period for autism, to assess maternal and child compliance. Further, we will analyze a subset of maternal wristbands to assess variation over time and validate methods in a local laboratory.

Finally, we will determine which compounds are associated with early ASD signs and cord epigenetic ASD biomarkers in the subset with analyzed bands to guide future ASD risk factor investigations.

Co-effects of inflammatory cytokines and PCB-95 exposure on human neuronal cell differentiation

• Principal Investigator: Judy Van de Water (javandewater@ucdavis.edu), School of Medicine, Department of Internal Medicine

The problem: Immune system molecules called cytokines have the potential to mediate negative effects on developing neurons, as they are diffusible molecules that have various different functions in the nervous system. We recently demonstrated that mothers of children with autism and intellectual disability have a unique cytokine profile during pregnancy when compared to mothers of children with autism without intellectual disability.

In a pilot study, we screened an inflammatory cytokine mix (ICM) in a human neuronal cell line. We found that ICM leads to changes in signaling inside the cell, opposing effects on process length and total outgrowth per cell between days three and six, and decreases measures of cell health after 24 hours. Studies also indicate that exposure to certain environmental toxicants like PCBs is associated with immune system dysfunction, as well as impairment of the developing nervous system.

The project: To determine the combined effect of an inflammatory cytokine mix, and PCB-95, we will culture LUHMES cells with the ICM mix alone, PCB-95 alone and a mixture of the two exposures and measure toxicity. We will measure various functions of the cells to determine if they change their growth pattern.

These studies will provide the basis for expanded studies in the future to better understand the combined effects of inflammation and toxicant exposure on developing neurons.

Contact

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