By Lisa Merkl
University Communication

Thanks to a $3.2 million grant from the Environmental Protection Agency (EPA), a group of University of Houston researchers is leading a project that will enhance scientists’ understanding of how industrial chemicals in the environment can harm human health and development.

The Texas A&M Institute of Genomic Medicine and Indiana University are also participating in the UH-led study.

The primary aim of the three-year grant is to contribute to a more reliable chemical risk assessment that will provide clues to how certain chemicals affect human health.  This will provide researchers with a wealth of new information about what toxins may cause serious diseases. 

The UH group is led by Jan-Åke Gustafsson, Robert A. Welch Professor in the biology and biochemistry department and director of the Center for Nuclear Receptors and Cell Signaling.  Joining Gustafsson is Maria Bondesson, research assistant professor of biology and biochemistry, and post doc Catherine McCollum.  All three are part of UH’s College of Natural Sciences and Mathematics. 

“There are so many industrial chemicals in the environment – more than 80,000 – but only a few are tested for their danger levels and, moreover, the synergies between them aren’t being analyzed,” Bondesson said.  “One barrier to the current methods of testing such toxins has been that rats and mice are only exposed to one chemical at a time, which slows down the assessment of risks and does not address the fact that people are exposed to several chemicals at once in real life, many of which interact with each other.” 

A main goal of this multidisciplinary research will be to include finding ways to speed up the testing process and decrease the costs.  This can be done through the use of zebrafish in the studies to be performed at UH, which is a new approach that will complement Texas A&M’s use of mouse embryonic stem cells in this project. 

Zebrafish breed in large numbers at a rate of up to 200 embryos in one cycle, thereby being less expensive to use. Another advantage of using zebrafish is that they have a fast embryonic development, with their embryonic organ formation taking days, as compared to mice taking weeks and humans, of course, taking months.  This rapid development of zebrafish gives scientists the capacity to analyze many samples in a short time. There are, however, a number of similarities between fish and mammals with regard to developmental pathways, and about 75 percent of their genes are the same. 

Once the respective fish and rodent embryonic stem cells are exposed to toxins ranging from arsenic to chloroform, both groups – UH and A&M – will analyze the chemicals’ affect on the embryonic development of the neurons and central nervous system, heart, blood and blood vessels, as well as an early developmental process called gastrulation. 

From the zebrafish and mouse data, Indiana University will use the fish and rodent results to build computer models that can simulate the effects of chemical exposure.  In other words, virtual toxins can be created to eliminate the use of actual toxins and need for mammalian and fish testing, replacing them with computers. 

By incorporating the collective results and subsequent computer models developed during this research project into other screening projects that are being performed in the United States and Europe, researchers will be able to better prioritize chemicals for further risk assessment, with new methods for the screening of developmental adverse effects in zebrafish and mouse embryonic stems cells that are relevant for human embryonic development.