1. Development of a High-Throughput Assay to Identify 5-α Reductase Inhibitors for Orthogonal Evaluation in an Androgen-Dependent Human 3D Prostate Microtissue
Leads: Chad Deisenroth, Josh Harrill, Menghang Xia
Goal: Develop additional human-based, cellular tests to more completely model androgen pathway activity.
- Issue: Environmental factors that alter the metabolism or bioactivity of androgen, a male sex hormone, can harm human reproductive and sexual development. Current guidelines rely on animal testing to evaluate the potential for certain chemicals to disrupt normal androgenic functions. Efforts to evaluate androgen-active chemicals using predictive computational models with in vitro data are limited; unlike animal models, computational models have insufficient coverage of key metabolic outcomes and observable characteristics resulting from gene-environment interactions.
- Project Focus: Develop a high-throughput assay to evaluate the effects of blocking the activity of enzyme 5α-reductase and develop a 3-D human prostate microtissue assay that may enable better assessments of androgen-active chemicals. Together, the assays can provide greater depth for predicting the negative effects of androgen-disrupting compounds.
3. Profiling Environmental, Drug, and Food-Related Chemicals that Inhibit Acetylcholinesterase Activity
Leads: Menghang Xia, Michael Santillo
Goal: Develop a high-throughput in vitro test system to identify and characterize new compounds that block the activity of acetylcholinesterase.
- Issue: Acetylcholinesterase (AchE) inhibitors are compounds related to foods, drugs, and the environment that can be toxic to humans.
- Project Focus: To advance existing methods, metabolism will be incorporated into the in vitro screening system, which, in addition to in-depth mechanistic studies, may improve the ability to detect emerging chemical hazards.
- Publications: “Use of high-throughput enzyme-based assay with xenobiotic metabolic capability to evaluate the inhibition of acetylcholinesterase activity by organophosphorous pesticides.” Li S, Zhao J, Huang R, Santillo MF, Houck KA, Xia M; Toxicology in Vitro, 2019, 56:93-100. http://www.sciencedirect.com/science/article/pii/S088723331830540X