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Cholesterol Research, Begun in the ‘Little Skate,’ Garners Award

Wednesday, October 01, 2008

New research on the way the body processes cholesterol has earned a scientist at the University of Rochester Medical Center one of the highest honors in the field.

Ned Ballatori, Ph.D., professor of Environmental Medicine, has been awarded the Adolf Windaus Prize for his discovery of key molecules involved in the way the body handles cholesterol and other lipids. Ballatori discovered a protein complex called OST (organic solute transporter) that plays a key role in how our body processes cholesterol and offers researchers a new target in their quest to help people lower their cholesterol and stave off obesity, heart disease, and diabetes.

Ballatori did the initial research in a fish known as the “little skate,” a close cousin to the stingray, that cruises the cold Atlantic waters off the East Coast. The fish has roamed Earth’s waters for 450 million years. While it might be difficult to see how a little skate resembles humans, there are enough similarities biologically that scientists like Ballatori can spend years exploring the genetics and biological workings of the fish, all with an eye toward improving human health.

And that’s precisely what Ballatori has been able to do. In little skates, he was able to explore a research area known as membrane transport much more thoroughly than he could have in humans. And in the little skate, Ballatori discovered two proteins that had been previously unknown that control how the fish handles lipids like cholesterol. The two proteins work in tandem, and Ballatori was able to track down the genes that encode for these two proteins simultaneously by studying the fish.

Ballatori then went on a sort of fishing expedition and found similar versions of the proteins in people. He found that the proteins are central players in the handling of cholesterol and other lipids, thus opening the door to a potential whole new avenue of treatment for millions of people with high cholesterol.

The protein complex that Ballatori discovered, OST, helps the body recirculate and re-use bile acids, which are made in the liver from cholesterol and are important for digesting fat and for regulating the body’s cholesterol levels. Scientists believe that if they inhibit OST, it’s likely that cholesterol levels would drop. In Ballatori’s experiments, mice in which OST has been turned off have lower levels of cholesterol and triglycerides.

A new drug that targets OST would be a welcome addition to medications currently used to treat high levels of bad cholesterol and triglycerides. Many patients have a difficult time with current medications, whose uses can be limited by risks such as kidney and liver damage.

The prize, awarded by the Falk Foundation of Germany, is named after Adolf Otto Reinhold Windaus, who won the Nobel Prize in chemistry in 1928 for his work on molecules like cholesterol. The prize, given only once every two years, was awarded earlier this year at the International Bile Acid Meeting in the Netherlands.

Ballatori received his bachelor’s and doctoral degrees from the University of Rochester and joined the faculty in 1987 after completing a postdoctoral fellowship at Yale University School of Medicine. He serves as the deputy director of the University's Environmental Health Sciences Center and the Center for Comparative Toxicology at the Mt. Desert Island Biological Laboratory in Salsbury Cove, Maine, where he performs much of his research on the little skate.

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