Mechanisms of adult-onset and transgenerational disease due to endocrine disrupting compounds

PI: Tracie Baker, DVM, PhD

Studies have shown that endocrine disrupting compounds (EDCs) can have a profound effect on development, reproduction, and the immune system, but understanding how fetal and childhood exposure to EDCs causes disease in adulthood is a significant human health challenge. Variable exposure levels and genetic backgrounds add confounding variables, as well as the long latency between exposure and response, which can match the life span of researchers, making it difficult to connect cause and effect. Our previous studies in zebrafish have shown that exposure to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a known endocrine disrupting compound, leads to spinal deformities, male/female sex reversal, and transgenerational inheritance of decreased reproductive capacity that is mediated through the male germline. We aim to inform the connection of toxicant-induced phenotypic and functional abnormalities from multiple generations with changes in genome function and epigenetic regulation, as well as to identify critical windows for biomarkers of effect and interplay among pathways mediating toxic endpoints.

Investigating occurrence of health effects due to environmental contaminants in Detroit waterbodies

PI: Tracie Baker, DVM, PhD

Scientific and public concern is growing in response to ongoing reports of contaminants in waterways due to their potential effects on human and wildlife health. These contaminants include pharmaceutical, personal care, agricultural, and industrial byproducts that enter the waterways via purposeful dumping, runoff, and wastewater treatment plants. The overall project goals are to 1) determine the level of known contaminants in Detroit waterbodies and 2) assess whether chronic exposure to these contaminant mixtures can affect health outcomes This study has potentially broad implications for identifying etiologies of environmentally-induced disease in people and anthropogenic pressures on the health of wild fish populations in the Great Lakes system.

Kids Without Cancer – Zebrafish Initiative

PIs: Tracie Baker, DVM, PhD, Jeffrey Taub, MD, and Ryan Thummel, PhD

Acute leukemias are the most common form of childhood cancer in industrialized countries, including the United States, and are the leading cause of death from disease among American children. The interaction of host genetic susceptibility and environmental/exogenous factors likely interact in the development of leukemia. Using transgenic zebrafish with TEL-AML1 (the most common chromosomal abnormality in childhood acute lymphoblastic leukemia) to study the effects of exogenous exposures has a potentially wide impact as it aims at testing whether compounds in common pesticides represent a trigger for childhood acute lymphoblastic leukemia. Understanding environmental factors in leukemogenesis may render leukemia a more preventable disease.

The use of novel assay systems to evaluate cardiac, reproductive, and neurobehavioral effects of volatile organic chemicals (VOCs) in aquatic model organisms

PI: Tracie Baker, DVM, PhD
Co-PIs: David Pitts, PhD and Shawn McElmurry, PhD

Volatile organic compounds (VOCs) are environmental pollutants of emerging interest, but little is known about the long-term human and environmental health effects of VOC exposure. Numerous VOCs are present in manufacturing and building materials, home furnishings, pesticides/fertilizers, and consumer products, thus VOCs are ubiquitous in indoor spaces, agricultural fields, landfills, contaminated areas (e.g. Superfund sites, industrial complexes), and groundwater. The development of novel exposure systems and the use of two NIH model organisms (Daphnia and zebrafish) represents an innovative approach to study VOC toxicity, and will be ideal for high throughput evaluation of VOCs, thus having a potentially wide impact to test whether ubiquitous environmental chemicals are a trigger for adverse cardiac, reproductive, and neurobehavioral outcomes.

Emerging and Endocrine Disrupting Chemicals in Detroit Drinking Water

PIs: Tracie Baker, DVM, PhD and David Pitts, PhD

Detroit, Michigan is a post‐industrial city situated on the banks of the Detroit River, which receives contaminants from the discharge of wastewater treatment plants, landfill leachate, and run off from rapidly developing urban gardens and agriculture, demolished and abandoned infrastructure, and storm water from impervious surfaces. In addition, significant inputs of contaminants via atmospheric deposition occur from the transitioning post‐industrial landscape. These complex mixtures of contaminants can have synergistic, antagonistic and additive adverse effects on endocrine function in wildlife and humans at very low levels (e.g., ppb, ppt) of exposure. This project will characterize contaminants of emerging concern that are known or suspected to be endocrine disrupting compounds, and develop a customizable array as a proof of concept tool that will be useful for the evaluation of estrogenic and anti‐androgenic activity in samples of surface, ground, and infrastructure water.

The occurrence of microplastics in drinking water treatment systems and the consequential impact on ecological and human health

PIs: Tracie Baker, DVM, PhD and Yongli Zhang, PhD

Microplastics (MPs) are defined as plastics smaller than 5mm in size, including microbeads, fragments, and fibers. A recent survey of 159 tap water samples taken from several countries showed that 83% contained MPs with the highest densities of MPs per volume found in North American water samples. The critical questions are (1) how do MPs pass through water treatment and get into our drinking water and what is the consequential impact on ecological and human health; and (2) how to improve drinking water treatment, the critical public service protecting human beings from exposure to pollutants, to efficiently remove MPs and prevent exposure risks? The overall research goal is to address the emerging public health concern of MPs in drinking water systems and to provide the knowledge base for targeted and improved control/prevention strategies.