EDGE awards pilot grants to four new research projects

The University of Washington (UW) Interdisciplinary Center for Exposures, Diseases, Genomics & Environment (EDGE) recently awarded four research teams with pilot grants of $40,000 each to support novel lines of research in environmental health science. Each year the EDGE Center provides these grants to investigators who propose research that represents a departure from their established line of inquiry. The funding is intended to help lead to successful proposals for larger grants by providing preliminary data. UW researchers from a wide range of disciplines are welcome to apply, and one project is typically awarded a supplement of $10,000 to support community engagement. This year's awardees will explore important challenges in environmental health by applying diverse approaches from toxicology, omics, and epidemiology to environmental engineering. Their projects are as follows:

Defining novel gene X environment interactions that lead to embryonic heart defects

Lisa Maves

University of Washington School of Medicine, Seattle Children's Research Institute

Congenital heart defects (CHDs) are one of the most common birth defects, affecting over 1% of live births. Despite significant effort, fewer than half of the causes of CHDs have been identified. Complex interactions between genes and environment are thought to play a role, but understanding these interactions is challenging. Phthalates are plasticizer chemicals that are commonly found in our environment. With her new EDGE Center pilot grant, Lisa Maves will test the hypothesis that embryonic exposure to phthalates can magnify the effects of genes that are associated with CHDs, leading to impaired heart development. She will use zebrafish because they are a well-established model for both understanding the genetics of heart defects and for assessing the effects of environmental toxicants, although these two systems have rarely been explored in relation to each other. One aim of the study is to screen for phthalates, phthalate replacements, and phthalate metabolites that disrupt heart development. A second aim is to test whether phthalate exposure interacts with CHD gene mutations to affect heart development. Improving our understanding of CHD genetics and environmental interactions can help inform families with genetic risk for CHD that may benefit from monitoring their chemical exposure risk. “This project will help us take a new approach to understanding how environmental chemicals may impact heart defects,” said Maves. “This project may also help us identify safer phthalate replacement chemicals.”

Development of a phthalate-disrupted placental multi-omic network

Alison Paquette and Samantha Lapehn

Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Medicine

Phthalates are chemicals commonly added to plastics to make them more flexible. Exposure to phthalates during development is associated with a range of negative outcomes such as preterm birth, delayed language acquisition, autism spectrum disorder, and attention-deficit/ hyperactivity disorder. The placenta is likely to mediate many of these effects, given the critical role it plays in maternal-fetal communication, hormone production, and exchange of oxygen, nutrients, and waste. Alison Paquette and Samantha Lapehn have previously shown that exposure to phthalates during pregnancy is associated with changes to gene expression in the human placenta. In particular, they noted that many changes were associated with a specific phthalate—diisononyl phthalate (DINP) which is understudied compared to other phthalates. Now they will be using an array of endpoints to construct a “multi-omic network” to evaluate the effects of DINP on gene expression in placental cell lines. These endpoints include mRNA, microRNA, and proteins. They will use sequencing, mass spectrometry, and statistical methods to explore and describe the multi-layered regulatory effects on gene expression following phthalate exposure. Support with analysis will be provided by the EDGE Center’s Genomics, Bioinformatics & Biostatistics, Microphysiological Systems Facility Core. “This research will provide more information on how phthalates may affect placental function during pregnancy, which can impact health throughout the lifespan,” said Paquette.

Residential proximity to harmful algal blooms and risk of incident dementia in a Southern California electronic health record cohort

Joan Casey and Marissa Childs

University of Washington Department of Environmental and Occupational Health Sciences

Alzheimer’s disease and Alzheimer’s related dementia are growing concerns, affecting 11.5% of older U.S. adults in 2014 and potentially afflicting 15.2% by 2050. Some environmental exposures such as air pollution are known to be risk factors for Alzheimer’s disease. Other, lesser-known risk factors, like harmful algal blooms caused by waterborne cyanobacteria, may also be important. Harmful algal blooms expose humans to toxins via the air, water, or consumption of aquatic plants or animals and have been tied to the development of Lou Gehrig’s disease, another neurodegenerative disease. Despite multiple reasons to suspect that harmful algal blooms may contribute to the development of dementia, such a possibility has not received significant research. In this pilot study, Joan Casey and Marissa Childs will explore the connection between harmful algal blooms and dementia by leveraging existing electronic health records from over 1.5 million Kaiser Permanente Southern California members over the age of 60. First, they will identify the distribution of harmful algal blooms across space and time in nine Southern California counties from 2008-2023. Next, they will evaluate the association between average residential exposure to harmful algal blooms and the risk of dementia. This study represents the first large-scale epidemiologic study of exposure to freshwater harmful algal blooms and dementia. “Through this work, we hope to inform people in Southern California about potential neurological risks of living or recreating near harmful algal blooms,” said Casey.

Collectively Addressing Lead Contamination of Drinking Water in Washington State Schools

Katya Cherukumilli

University of Washington Department of Human Centered Design & Engineering

Lead in drinking water in U.S. schools and childcare facilities is an urgent public health concern, potentially exposing millions of schoolchildren to a neurotoxicant that impacts the way they grow, learn, think, and behave. Despite federal regulation of lead in fuel, paint, food cans, plumbing materials, and public drinking water supplies, current federal policies are too lax to protect public health, leaving this responsibility largely to the states. Washington State has a state-wide dataset of water lead levels in schools and abundant state-mandated funding available for lead remediation. However, for reasons that are unclear, few school districts have applied for this funding. For this project, Katya Cherukumilli will work with Washington school districts, health officials, and community partners to collectively study and address the problem of lead contamination of drinking water in schools. Specifically, she and her team will aggregate datasets on water quality, school infrastructure, and student demographics to map the prevalence and severity of threats from lead contamination of drinking water fixtures in schools. Next, they will interview superintendents and staff in high-risk regions to characterize the motivations and barriers of school districts to remediate lead-contaminated water. In parallel, they will conduct a state-wide online survey to characterize the available resources, knowledge gaps, and/or priorities of school districts to address current and future environmental health issues. Finally, they will support schools in adopting appropriate lead remediation approaches by collaborating with state agencies and community partners to co-develop actionable web-based tools and educational materials about water quality testing and treatment. To support this community engagement, the team was awarded an additional $10,000. Cherukumilli said her team's work will “contribute to a new body of evidence that will inform the development of effective science communication and dissemination strategies to support safe water management in public institutions.”