Upham Awarded R21 Grant to Develop High-Throughput Toxicity Screening Assay

December 21, 2020

IIT-affiliated faculty member, Brad Upham, was recently awarded a $445,403 National Institutes for Environmental Health Sciences R21 grant for his project, “High-throughput toxicity screening of environmental contaminants and drug candidates using a novel gap junction intercellular communication bioassay in lung and liver cells.”

In recent decades, new “emergent” chemicals used in industry, transportation, agriculture, and urbanization are entering the environment at increasing levels as hazardous wastes that are often nonbiodegradable. Many of these emerging contaminants have been discovered and quantified in living organisms, including humans; however, the adverse health effects to environmental exposure on wildlife and the general population are largely unknown. With this grant, Upham will be developing a new screening system to identify environmental contaminants or drug candidates that can cause adverse health effects. The development of this new screening system will provide additional and critical new information to assess the potential toxicity of these emergent chemicals in our environment.

In vitro high-throughput screening (HTS) assays have been widely applied as an alternative to animal-based testing in determining the toxicity of environmental contaminants and drug candidates. Current HTS studies provide the community with rich toxicology information and the biological endpoints chosen for HTS determines the toxicological relevance. Although many biological endpoints exist for HTS, there is still a need to incorporate further endpoints to achieve a more comprehensive assessment on the potential adverse health effects of environmental contaminants and potential drug candidates.

The novelty of the assay being developed by Upham relies on a molecular endpoint responsible for coordinating normal functions in tissues by integrating cell-to-cell signaling through gap junctions. Gap junctional intercellular communication (GJIC) is essential for maintaining normal tissue function by allowing the cells to coordinate their biological roles in a tissue. Interruption of this intercellular signaling can result in tissue dysfunction. The new screening tool developed by Upham will be able to process large numbers of samples.

The new screening system developed by Upham can help identify potential adverse health effects at the early stages of drug development, thus potentially reducing the cost to the supplier and the consumer. “Today, drug industries face unprecedent productivity challenges due to financial pressures driven by the increasing cost of bringing a drug to market. Identifying potential adverse health effects at the early stages of drug development will significantly drive down the cost of potential new drugs,” commented Upham.