Monday, July 3, 2017

Michael Duffel conducts basic research to provide vital insights for other scientists to use when designing better drugs and fighting toxic chemicals.

Duffel, BS, PhD, is a professor in the college’s Division of Medicinal and Natural Products Chemistry (MNPC) within the Department of Pharmaceutical Sciences and Experimental Therapeutics (PSET).

He is also the Associate Dean for Research and Graduate Programs. Currently, Duffel is studying polychlorinated biphenyls (PCBs): some of the most environmentally-persistent toxic chemicals humans have ever made. Duffel is most interested in PCBs in the air and how they can affect human health on a molecular level.

PCBs were manufactured in the United States from 1929 until the 1970s. They were used in electrical transformers, plasticizers, lubricants, paints, adhesives, caulk, fluorescent light ballasts, and many other applications. Despite a 1979 ban on intentional production, PCBs do not readily degrade and therefore still remain in our air, water, and soil. There are also emerging sources of PCBs such as contamination of some paint pigments due to unintentional formation during the manufacturing process.

PCBs have been linked to a variety of adverse health effects—from cancer, diabetes, and cardiovascular disease to thyroid hormone abnormalities and other endocrine-based disease. In addition, PCBs can negatively influence infant and child development. One increasing concern is airborne PCBs in older buildings such as some school buildings that were built during the time when PCBs were commonly used. For this reason, some school districts have begun replacing PCB-laden caulk and other sources in buildings.

“You have children and teachers that are in these schools eight hours a day or more. The air concentrations may be relatively low, but you’re constantly inhaling those PCBs. We still don’t really know if there is a safe level and, if so, what it is,” Duffel said.

Enzymes that are present in human bodies change PCBs to make them more or less toxic; just as they do when someone takes medicine. Duffel’s team of graduate students and collaborating scientists conduct basic research to piece together exactly how certain enzymes in a person’s body act after someone takes a medicine or breathes in PCBs.

“Learning more about the role these enzymes play when toxic chemicals are introduced to the body helps us understand how they metabolize drugs, where they are also involved,” Duffel said.

By learning about how enzymes behave when drugs and chemicals are introduced to the body, scientists are one step closer to being able to introduce drugs that augment good reactions and dampen bad ones.

“The challenge is to be able to predict how a metabolic enzyme will interact with chemicals. And if you can do that, then you get a better idea of how to design a drug that will do what you want it to do, and then leave,” Duffel said.

Duffel expects that other types of scientists will draw from his results when designing drugs with fewer side effects and drug interactions. He also hopes to one day see a drug come to market that reduces the toxic effects of PCBs.

As tends to happen with basic research, while studying one topic, surprise breakthroughs may be made in other areas. Last year, Duffel’s group published a finding related to their work which may inspire new strategies for designing drugs for several hereditary amyloid diseases that affect the heart and nervous system.

While Duffel’s research is very specific, it is part of a larger effort to research the health effects of PCBs in our environment through the Iowa Superfund Research Program. This center is funded by the National Institute of Environmental Health Sciences and brings together a broad range of experts across five UI colleges to explore many facets of airborne PCBs: Their sources, distribution in the environment, mechanisms of toxicities, determination of exposure levels, and novel methods of microbial- and plant-based environmental cleanup, to name a few.

Duffel is the associate director of the Iowa Superfund Research Program and leads a basic research project within the program.