Superfund Research Program
Single Cell, Multi-Parametric High Throughput Platform to Classify Endocrine Disruptor Potential of Mixtures
Project Leader: Michael A. Mancini (Baylor College of Medicine)
Co-Investigators: Fabio Stossi (Baylor College of Medicine), Adam T. Szafran (Baylor College of Medicine)
Grant Number: P42ES027704
Funding Period: 2017-2022
Project Summary (2017-2022)
Human health is at risk due to environmental exposures to a wide range of chemical toxicants and endocrine disrupting chemicals (EDCs). EDCs are commonly found in natural and industrial sources and represent a large and growing family of compounds and mixtures with high chemical diversity. The Texas A&M Superfund Research Program (TAMU SRP) Center is focused on evaluating and reducing the human health risks posed by exposure to hazardous substances, including EDCs, that are mobilized from sediments and other sources by environmental disaster events such as tropical storms, hurricanes, and floods.
The overarching goal of this project is to develop fast, robust, and cost-effective assays to determine the endocrine disrupting potential of complex, environmentally relevant chemical mixtures in the highly industrial Galveston Bay/Houston Ship Channel area (GB/HSC) and other Superfund sites. The availability of a set of fast, sensitive, and reproducible EDC assays will facilitate health hazard evaluation and improve decision-making in response to environmental emergencies.
The researchers are testing the hypothesis that multi-parametric, highly mechanistic contextual in vitro assays, and bioinformatics analyses serve as a robust, fast, and cost-effective framework to evaluate the endocrine disrupting potential of environmentally-derived complex chemical mixtures. Nuclear Receptors (NRs), a large class of transcription factors, are key mechanistic targets of EDCs. The assays being developed in this project focus on three NRs identified by the Endocrine Disruptor Screening and Testing Advisory Committee: estrogen receptor (ER), androgen receptor (AR), and thyroid hormone receptor (TR).
The researchers are using advanced high throughput imaging and image analysis and integrative bioinformatics to address critical needs in assessing the risk to human health posed by hazardous substances. They are developing fast, robust, and cost effective high throughput assays to identify the presence of EDCs and classify their bioactivity. Cell-based platforms in endocrine-relevant systems are being used to analyze both single compounds (~50, including heavy metals, pesticides, pharmaceuticals, etc.), and complex mixtures, including samples from Superfund sites.
The research team is also assessing the endocrine disrupting potential of chemical mixtures in the environment. While previous work has primarily focused on EDC activity of single compounds mediated by the ER, they are increasing the scope and relevance of EDC assessment by measuring effects on AR and TR, and by moving from single compounds to mixtures. High content and cell-based data is being translated into a bioinformatics-based framework to determine and predict the endocrine disrupting potential of complex, environmentally relevant chemical mixtures.