University of Wisconsin-River Falls

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Oct. 1, 2004


UW-RF Computer Prof Studies the Human Heart

Scholarly papers titled "Gating currents associated with intramembrane charge displacement in HERG potassium channels" might seem more appropriate from a medical school than a business college.

But such writings are the product of extensive research conducted on the human heart by computer science Assistant Professor Anthony Varghese in the College of Business and Economics at UW-River Falls.

For a decade Varghese has been on the cutting edge of human physiology research that has resulted in a dozen scholarly treatises published in some of the leading human physiology journals in the world. They are the outcome of research conducted with colleagues while Varghese was at such institutions as Oxford University, The Johns Hopkins University, and the University of Minnesota. He has worked with U.S. Army super-computers and in the research laboratories of the Veterans Administration.

He has applied his bench research directly while consulting with such companies as Medtronics to improve its defibrilators; with Physiome Science (now Predix Pharmaceuticals), which used computer models to support clinical trials of a proposed drug on humans and subsequently convinced the FDA to approve a new drug; and for Endocardial Solutions, Inc., where he improved the design of software used in an operating room computer that enables cardiologists to effectively map the inside of a beating human heart.

These experiences have been brought back into the classroom at UW-River Falls where Varghese shares his particular expertise with his students: setting up programs on computers to enable them to resolve complex problems, regardless of the problem's content.

In Varghese's case, the subject has been human physiology. The programs he's designed have allowed him to assist medical scientists in two distinct areas: understanding the fundamentals of how human heartbeat is regulated; and modeling the interaction of drug therapies before they are launched in laboratories and then introduced to humans in clinical field trials.

His interest was first piqued as an undergraduate student at UW-Platteville, where he explored basic circuit theory on an IBM mainframe computer. "I really liked it. It solidified all that I knew about electrical circuits."

He went to the University of Minnesota where he was given access to U.S. Army super computers. His task was to assist in coming up with the methodology of program design techniques that would enable a super computer to work on large tasks that could not be stored on a desktop computer.

Collaborating with a faculty member, he used the super computer to simulate a human's most critical electrical circuit: the heart. His specific research studied the flow of ions through the heart's pacemaker cells that regulate its beat. Although few in number—all of them combined in a typical heart would be the size of a fingernail—they are crucial to humans.

If scientists, pharmaceutical companies and physicians understand how those cells work, then they can comprehend irregularities in heart beat that lead to sudden death, Varghese explains. "If you could understand some of the basic mechanisms then you could try to figure out the therapies. So I was interested in how drugs affect the proteins of the heart," Varghese said.

Varghese says his doctoral research contributed to the existing knowledge, but that much research needs to be continued. His expertise in designing computer programs to model human physiology led him into a new area of research he's pursued since leaving Minnesota: Human Ether-a-go-go, or HERG.

While the name may sound whimsical, the application is anything but. Varghese explains that HERG was isolated at UW-Madison and the University of Utah almost simultaneously. The research discovered that introducing mutant fruit flies to ether would affect a specific protein ion and make them shaky.

That same protein is found throughout the human body and directly affects heartbeat. The importance of HERG is now considered so essential that the U.S. Federal Drug Administration requires that every new cardiac pharmaceutical must be tested to ensure it doesn't negatively affect HERG.

In recent years Varghese has collaborated with colleagues throughout the world to study HERG and admits that the research has become very esoteric. In addition to his computer modeling, he also has spent time directly studying human cells under a microscope while subjecting them to electrical pulses at the VA Research Hospital in Minneapolis. He continues his HERG research in the summer.

Currently he spends most of his time working on bioinformatics computer programs to design scientific experiment protocols that are used by researchers as a model to guide their actual laboratory experiments.

He notes the use of computers are essential since the laboratory experiments typically involve a tiny strand of DNA. Varghese employs computers to search the entire human genome of millions of DNA sequences to ensure the experiment won't have unintended consequences on some other part of human physiology.

At UW-RF, Varghese has worked with his computer science students both to assist him in his research as well as in the networking of computers to resolve complicated problems.

That latter process is known as "clustering" or "griding," Varghese says, and it is becoming more prevalent throughout industry. He notes that by networking their computers, companies will often borrow computing time at night from stations across all sectors of their business and devote them to solving complex problems.

Last year Varghese guided his students as they set up a cluster in a business laboratory. "The students did it; they showed that it can be done." He adds that a grid can offer powerful computing ability.

Varghese hopes that as the University gains back some of its faculty and laboratory support money cut during recent years that he will be able to pursue more cluster activities. He says the exercise will prove beneficial to students in their value as employees to business and industry, as well as providing computing capacity to other faculty across the University who might want to model the problems they are researching.

"There are many opportunities out there," Varghese says of UW-RF's potential for harnessing the computational power of computer clusters.

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