Two UT Health Center scientists receive $2.2 million from NIH for research leading to treatments for heart disease, stroke

Monday, October 17, 2005

Two scientists at The University of Texas Health Science Center at Tyler have received $1.1 million each from the National Institutes of Health to further their research into how the blood-clotting process works.

Pierre Neuenschwander, Ph.D., an associate professor of biochemistry, is using his grant to study a protein called factor IXa that plays a crucial role in the clotting process (IX and the other factors are read as Roman numerals). Vijay Rao, Ph.D., professor of biochemistry, is using his NIH grant to investigate the role of another protein, factor VIIa, in blood clotting. Each NIH grant is funded for four years.

Dr. Neuenschwander said studies have linked increased activity of factor IXa and an associated protein, factor VIII, to a higher risk of having blood clots that lead to strokes or heart attacks. These two proteins work together to clot blood. His research is designed to reveal how factor IXa works and how it is regulated.

People with too little factor IXa or factor VIII in their blood are subject to excessive bleeding or hemophilia. But people with too much of either protein face the opposite problem: a higher risk of clots forming and choking off blood vessels, resulting in strokes or heart attacks. "If you have too much of these proteins, you clot too fast or too much. There is a really fine balancing act involved," he said.

"We’re looking at the active part of factor IX, which is factor IXa," Dr. Neuenschwander said. "Factor IXa bites one protein in one place. It’s very specific." But how it recognizes the protein and decides where to "bite" is not very clear.

"If we could find something that inhibits factor IXa, it would be like putting a gag on its mouth to keep it from biting the protein. Finding a perfectly fitting gag could potentially lead to a drug to stop thrombosis," he said. In thrombosis, a blood clot forms inside a blood vessel and remains attached to the site where it formed.

Dr. Rao’s grant deals with two other clotting proteins: factor VIIa and tissue factor. His research seeks to answer a deceptively simple question: Why is it that blood clots quickly in some individuals, yet blood in other individuals continues to flow freely and does not clot?

"My lab focuses on working with cells to understand the process of clotting. Our team’s goal is to develop new anti-clotting proteins," he said.

"Cardiovascular diseases are the No. 1 killers in the United States. A stroke occurs when a blood clot forms in the brain. A heart attack is a blood clot in the aorta, the main blood vessel leading to the heart. If you stop the clotting, you can prevent strokes and heart attacks," Dr. Rao said.

He and his team are studying what happens when factor VIIa binds to blood cells or cells that make up the blood vessel.

"We want to know if factor VIIa stays on the cell’s surface or goes inside the cell. If it does the latter, where does it go inside the cell? And then we want to know if it comes back outside the cell. Knowing all of this will give us some idea how blood clotting is regulated," Dr. Rao said.

"If factor VIIa stays on the cell surface longer than needed, it may lead to thrombosis," he said. Factor VIIa works with tissue factor to start a series of reactions that ultimately end in clotting.

"I’ve been working on this for about 20 years. The clotting process is very complex and interesting," Dr. Rao said.

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