If Linda Knight’s hypothesis proved correct, thousands of people disabled or killed by blood clots each year could be saved by snake venom. But first she needed to see if her discovery worked in humans.

Translating research discoveries like Knight’s quickly from the lab to patients is what the Keystone Institute for Translational Medicine is all about.

For Knight, it all started 31 years ago, when she came to Temple University School of Medicine to conduct research on how to detect blood clots using imaging techniques. Knight, professor of radiology and research associate professor in the Sol Sherry Thrombosis Research Center, has a Ph.D. in radiopharmaceutical

In the late 1980s, researchers in the laboratory of Dr. Stefan Niewiarowski (now deceased) in the Sol Sherry Thrombosis Research Center at the School of Medicine were the first to discover that many snake venoms contain proteins known as disintegrins which attach to blood platelets. Platelets are part of the blood and responsible for hemostasis, or stopping of bleeding, by sticking together to form a plug. Helpful when sealing off a cut and stopping bleeding, platelets turn harmful when they form a blood clot that blocks a blood vessel.

Knight figured out a way to use a disintegrin as a tracking device for blood clots that would alert clinicians to a potentially dangerous blockage. By adding a radioactive tag to the disintegrin, she could then spot it, and the clots it attached to, on imaging tests.

The first step was laboratory research to show that the venom had potential. Over a three-year period, Knight and her research team studied purified disintegrins from eight different kinds of snake venoms, eventually narrowing it down to the one that worked best.

The second step took much longer, 10 years, and focused on how to purify and modify the snake venom disintegrin into an imaging agent that would be safe and convenient for use, paving the way to study the technique in humans. The team also figured out a way to create synthetic disintegrin so that they could produce larger quantities.

As soon as the venom project appeared to hold promise as the basis for an eventual imaging test for humans, Knight teamed with Alan Maurer, M.D., chief of nuclear medicine, to provide a physician's input on the need for such a test, how it might be used clinically, and more recently, to conduct human trials.

"In order for basic laboratory discoveries to reach the clinic, it is essential for laboratory scientists to work together with physicians who are interested in taking the idea forward into the clinic for patients, and who are willing and able to devote the time to research,” said Knight. “It has to be a team effort."

A phase I study, successfully replicating the results of the lab work and focusing on safety in human subjects, has been completed. A phase II study, which will focus on demonstrating that this technique can detect blood clots in humans, will begin soon.