Engineered Liver May Shed Light on Effects of Chemicals in the Environment

The liver is the primary organ in the human body that metabolizes foreign compounds such as drugs, alcohol, cigarette smoke, and environmental chemicals. Using the liver as an “alarm system,” researchers are starting to better understand the different levels of toxicity from these compounds and their effects on the human body.

One of these researchers is Padma Rajagopalan, director of the Virginia Tech Institute of Critical Technology and Applied Science’s Center for Systems Biology of Engineered Tissues. She is a past recipient of a National Science Foundation CAREER Award to fund her work on cell migration, and in the past two years she has received more than $1 million in funding to create and study engineered tissues that mimic the human liver.

Now, the U.S. Environmental Protection Agency has awarded one its three-year $750,000 Science to Achieve Results award that it calls STAR to Rajagopalan. T.M. Murali of Virginia Tech’s department of computer science is a co-principal investigator on this award and is also co-director of the systems biology center. Marion Ehrich of the Virginia-Maryland Regional College of Veterinary Medicine and co-director of its Laboratory for Neurotoxicity Studies will serve as a consultant on the project.

The newly funded work will take advantage of Rajagopalan’s in vitro three-dimensional liver mimic, an engineered functional tissue. As the liver plays a central role in the detoxification of the human body, the new project will establish this liver mimic as an effective model for studying the effects of different types of toxins on the liver.

Rajagopalan said, “With the increasing number of chemicals, such as pesticides, being used in agriculture and industry today, humans are exposed to these substances to much greater extents. However, we lack a comprehensive understanding of the cell- and organ-wide effects of mixtures of toxic substances and how interactions among them can lead to chronic health problems. These gaps in our knowledge pose fundamental barriers to preventing or mitigating life-threatening toxicant-induced health issues.”

This award will specifically look at chemically-driven liver damage resulting from exposure to carbon tetrachloride, found in cleaning agents among other products, and to dichloroethylene, used as a solvent in floor finishes such as waxes and lacquers, among other purposes.

With Murali’s expertise in computer science and bioinformatics , they will be able to establish a combined experimental and computational pipeline for toxicity testing and risk assessment based on three-dimensional liver mimics and biological process linkage networks.


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