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Multiple disease-related research gets green light from the NIH

Saranac Lake, N.Y. - Stephen Smiley, Ph.D., a member of the scientific faculty at the Trudeau Institute, whose research could lead to new treatments for several common diseases, has been awarded a research grant from the National Institutes of Health (NIH) for nearly $2 million.

Dr. Smiley and members of his laboratory are working to develop treatments for a number of diseases where an abnormal activation of blood coagulation pathways causes damage to the body. The diseases include multiple sclerosis (MS), rheumatoid arthritis, transplant rejection and sepsis, a leading cause of hospital deaths. In particular, Dr. Smiley's laboratory is studying fibrin, a blood-clotting protein that frequently accumulates at high levels in diseased tissues. These high levels of fibrin are thought to clog blood vessels and cause inflammation, thereby starving tissues of oxygen and increasing the severity of disease.

With prior funding from the NIH, Dr. Smiley's laboratory collaborated with Trudeau colleague Larry Johnson to demonstrate that, despite the risks it poses, fibrin also performs critical protective functions during immune responses.

The researchers showed that fibrin deposition is essential for survival during certain infections. Specifically, they found that fibrin staunches bleeding caused by protective immune cells as they rid the body of infected cells. In addition to protecting against this collateral damage caused by the immune system itself, Drs. Smiley and Johnson also discovered that fibrin suppresses the growth of some unhealthy bacteria.

These prior studies led the scientists to hypothesize that the human body needs to maintain a careful balance of proper fibrin levels during immune responses: "Some fibrin deposition is essential for good health, while too much can be dangerous and harmful," explained Dr. Smiley.

"I'm very pleased the NIH is continuing to support Dr. Smiley's research," said David L. Woodland, Ph.D., president and director of the Trudeau Institute. "Cutting-edge research of this caliber has the potential to lead to improved treatments for people afflicted with a number of debilitating diseases, in addition to those who suffer transplant rejections."

Dr. Smiley believes that prior attempts to treat patients suffering from sepsis by removing fibrin failed because those treatments most likely removed both unhealthy and healthy fibrin. With this infusion of research funds, Dr. Smiley's laboratory will now seek to identify what exactly tips the balance between healthy and unhealthy levels of fibrin. They recently discovered that cytokines, soluble signaling molecules within the immune system, play a primary role in regulating this balance. Now they are using a variety of models and methods to delineate precisely how cytokines regulate fibrin levels.

The NIH funds will support Dr. Smiley's research efforts over a four-year period.


Contact: Brian Turner
Trudeau Institute

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