Two UT Health Center scientists awarded grants from American Heart Association; postdoctoral fellow wins AHA fellowship

Friday, December 30, 2005

Two biomedical researchers at The University of Texas Health Science Center at Tyler have been awarded grants from the American Heart Association: Alexei Iakhiaev, Ph.D., assistant professor of biochemistry, and Ming Liu, Ph.D., associate professor of biochemistry. In addition, Samir Mandal, Ph.D., has been awarded an AHA Postdoctoral Fellowship. Dr. Mandal is the first UT Health Science Center researcher to receive this scholarship.

Dr. Iakhiaev received a two-year, $124,000 grant to study how the body prevents blood from clotting in places it shouldn’t, such as inside blood vessels. Blocked blood vessels can cause strokes and heart attacks.

“The purpose of the research is to identify the molecular interactions of the body’s natural anticoagulant, or anti-clotting, protein C system. We want to see how protein C is processed by the cells that line the blood vessels, as well as how it interacts with cells lining the airways and the pleural cavity surrounding the lungs,” Dr. Iakhiaev said. “The goal is to determine the molecular mechanism that maintains protein C in the body.”

Activated protein C, or APC, is currently used as a drug to prevent clotting inside blood vessels caused by sepsis, a dangerous condition with high mortality. But APC only lasts about 30 minutes in the bloodstream; after that it’s gone, Dr. Iakhiaev said.

“If we can prolong the time APC stays in the bloodstream, we can lower the amount of APC needed to treat sepsis and other diseases. It will be a better, more effective drug,” he said. APC is expensive, so reducing the amount used would also lower the cost of treatment.

“I’m trying to find the pathways, the ‘floodgates’ that eliminate APC from the bloodstream. If we can close those floodgates, we can prolong the time APC is in the blood at therapeutic concentrations,” Dr. Iakhiaev said.

Dr. Liu received a two-year, $124,000 grant to probe a process of protein modification called tyrosine sulfation, which occurs inside cells. Many proteins that undergo this modification end up being secreted outside the cell, he said.

“This grant focuses on those proteins involved in regulating hemostasis,” Dr. Liu said. Hemostasis has three components: the formation of blood clots, prevention of unwanted blood clots, and the lysis, or destruction, of blood clots. By studying how tyrosine sulfation affects the proteins involved in hemostasis, Dr. Liu will be able to examine how tyrosine sulfation affects blood coagulation, or clotting.

“It’s becoming obvious that this is a widespread type of protein modification. It has implications for many physiological processes. It not only affects coagulation, but also other processes such as how the immune system functions,” Dr. Liu said. His research may help determine the cause of abnormal hemostasis due to faulty sulfation of proteins. Results of his research could lead to new and better drugs or strategies to treat cardiovascular disease.

Dr. Liu has been conducting research into tyrosine sulfation since he was a postdoctoral fellow from 1984 to 1986 at Rockefeller University in New York. There, Dr. Liu worked with Professor Fritz Lipmann, who won the 1953 Nobel Prize in Medicine. Dr. Liu joined the Health Center in 1993.

American Heart AssociationDr. Mandal’s two-year postdoctoral fellowship totals $84,000. It will support him while he continues working closely with Vijay Rao, Ph.D., a professor of biochemistry at UTHSCT who studies blood coagulation. Dr. Mandal is investigating the role of cholesterol in blood coagulation. He has worked in Dr. Rao’s lab since he came to the Health Center more than four years ago.

“It’s pretty tough to get this fellowship. Only 6 to 8 percent of the people who applied were funded,” Dr. Mandal said. His winning research proposal aims to explore how cholesterol helps maintain cell structure. Too much cholesterol causes blood to clot. Dr. Mandal is examining how some cholesterol-lowering drugs affect blood clotting.

“This fellowship has allowed me to think independently and to work independently. This is the first stage of my career as a biomedical researcher,” Dr. Mandal said.

Dr. Rao said that Dr. Mandal’s track record in research, along with the high quality of his publications about his research gave him a competitive edge in obtaining this fellowship.

“The fellowship grant provides a great opportunity to Samir to expand his laboratory research and to develop his own record of independent research,” Dr. Rao said.

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