CAREER Award funds study of how estrogen-mimics affect cells

April 15, 2010

by Renee Meiller

An intricate biochemical messaging network, the endocrine system enables human bodies to grow and function properly throughout their lives.

Yet, in everything from children's toys and household products to food, agricultural land and our own lawns, humans daily encounter hundreds of natural and synthetic chemicals. Some of these compounds can interfere with the endocrine system and contribute to such adverse health effects as reproductive problems, hormonal changes, brain and behavior problems, impaired immune functions, and various cancers, among others.

In research funded via a prestigious National Science Foundation CAREER award, University of Wisconsin-Madison Biomedical Engineering assistant professor Pam Kreeger is developing methods for testing how endocrine disrupters affect cells.

In the normal endocrine system, glands secrete hormones that act as chemical messengers. These messengers are transported to target tissues, which express receptors for the hormones. In particular, Kreeger is interested in endocrine-disrupting chemicals that mimic estrogen, the primary female sex hormone. These chemicals act like estrogen, bind to the estrogen receptors in normal cells, and trigger some -- but not necessarily all -- of the functions in cells that true estrogen initiates.

However, these cellular responses vary depending on the type and concentration of the estrogen-mimicking chemical, the presence of other chemicals, and many other variables.

"Our interest is in how they differ," says Kreeger. "Can we predict a little better what parts of the cellular network will be affected by these different chemicals?"

With an approach that combines engineering, biological and mathematical tools, Kreeger and her students are developing models that will help them understand how cells sensitive to estrogen behave when exposed to these estrogenic mimics. Ultimately, they hope the models will enable them to interpret the role of estrogen receptor signaling in both normal and diseased states, such as cancer.

The research may help policymakers and the public make more informed decisions about the risks of using or not using products that contain certain chemicals-for example, bisphenol A, which may have negative health effects in children.

Kreeger will enable students to participate in her research, both in the lab and via the classroom. She is developing a course for both undergraduate and graduate students in systems biology and in summer 2010, will employ in her lab undergraduates from UW-Madison, the University of Puerto Rico-Mayaguez, and from St. Olaf College, a liberal arts school in Minnesota.

In addition, Kreeger plans to develop materials that demonstrate to high school students and teachers the connection between biology and math. Through work with the Mazomanie Science Outreach Outpost, she will share ideas that southern Wisconsin high school teachers can implement in their classrooms or at the outpost. She also will draw on the UW-Madison Science Alliance to reach public audiences via such interactive events as Science Expeditions and Wednesday Nite @ the Lab lectures.