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UW-Eau Claire Chemist and His Students
Collaborate with Marshfield Clinic Researchers

RELEASED: Sept. 10, 2007

Dr. David Lewis
Dr. David Lewis

EAU CLAIRE — Dr. David Lewis, a chemistry professor at the University of Wisconsin-Eau Claire, has received a $65,000 grant that will allow him, with the help of several students, to work in collaboration with a researcher at Marshfield Clinic on the development of new derivatives of the drug Warfarin.

The grant represents a partnership between the UW System and WiSys Technology Foundation Inc. to support projects with the potential to be a source of intellectual property and revenue in the future. As an inter-institutional research collaboration, the project also involves a $22,000 UW-Eau Claire campus investment. The mission of WiSys is to support research and education programs at UW campuses other than UW-Madison that have the potential to invigorate technology transfer and economic development throughout the state.

The UW-Madison campus is supported in this same mission by the Wisconsin Alumni Research Foundation, or WARF, the parent corporation of WiSys. Both corporations seek to protect licensed inventions or patents developed by UW scientists and return the proceeds of such work to the universities to fund further research.

Warfarin is an anticoagulant medication used to decrease the development of blood clots in people with disorders such as diabetes and heart disease. It is a synthetic derivative of coumarin, a chemical naturally occurring in a number of plants, but primarily in woodruff.

According to Lewis, Warfarin is so named because it was one of the earliest patented projects that came out of research supported by WARF. It was developed as a rat poison in 1948, and the acronym WARF was added to "arin" to indicate its link with coumarin.

Although its usefulness as a therapeutic anticoagulant was discovered in the early 1950s, and it was approved for use in humans in 1954, it wasn't until much later, in 1978, that researchers understood how Warfarin works. Coumarin works by interfering with the metabolism of vitamin K, which helps blood clot, so Warfarin and other drugs in this class are now known as vitamin K antagonists.

Lewis said he learned all this after he was approached by the executive director of WiSys, who introduced him to Dr. Michael Caldwell, a vascular surgeon and director of the Wound Healing Program at Marshfield Clinic in Marshfield. Caldwell, who uses Warfarin regularly with his patients, told Lewis that the main problem physicians encounter in using Warfarin is the variability of patient response. Some patients are extremely susceptible to its properties, while others are fairly resistant, so the dosage used is critical and must be monitored extremely closely through frequent blood testing in order to avoid side effects or injury to the patient.

In studying this problem, Caldwell and other Marshfield Clinic researchers believe they have identified genetic markers in humans that have helped help them improve their ability to predict patient responses to Warfarin from around 20 percent to as high as 70 percent, but they are also interested in finding new compounds that might provide alternatives to Warfarin.

This is where Lewis and his students come in, and one UW-Eau Claire senior chemistry student, Gina Macek of South Milwaukee, began working with Lewis on this research in July.

"Marshfield's work has identified how we need to modify Warfarin to improve it, and we are working to come up with some new compounds that might function reasonably well as alternative anticoagulants," said Lewis. "Basically, we are building modified molecules which then go back to Michael to be used in model testing systems.

As a side note, Lewis said this research is calling into question the current theoretical model of how Vitamin K works, possibly suggesting a new model, and he notes that work of this kind is really exciting, both for him and the students.

"Michael and I hit it off right away," said Lewis. "We bring very different perspectives to bear on the problem, but there was a synergy there immediately, from our first meeting, that is always the hallmark of a good collaboration. Sometimes he'll make a comment that will trigger a new train of thought for me, or vice versa, and we'll end up engaging in a kind of intellectual leap frog."

The current WiSys grant will run for one year, with the potential for a second, but Lewis plans to go to the National Institutes of Health for additional support, so he believes this could become a long-term project.

"That means there will be the potential for many UW-Eau Claire chemistry students to be involved in this work in the coming years," Lewis said.

For more information, contact Lewis at 715-836-4744 or lewisd@uwec.edu.

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