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Zebrafish’s Regenerative Abilities Make it Unique Tool to Study Disease

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Duke Health News 919-660-1306

DURHAM, N.C. -- Those unassuming minnowsized striped tropical fish swimming around in many household aquariums may hold the key to repairing cardiac muscle in humans hit by a heart attack.

The common zebrafish, named for the five stripes on its side and known scientifically as Danio rerio, can regenerate organs and tissues. This ability, which some other fish and amphibians have but mammals do not, has spawned a school of investigators seeking to unlock its mysteries. Among those fishing for clues is Kenneth Poss, Ph.D., a cell biologist at Duke University Medical Center.

"Zebrafish organs carry out the same basic functions as human organs and are subject to similar diseases and disorders," Poss said. "Many human conditions, such as heart failure, Alzheimer's disease and spinal cord injuries, result from tissue damage of some sort. If we can figure out how zebrafish regenerate these tissues after damage, we should gain new insights in possible therapies for humans."

Although zebrafish can regenerate many tissue types, including the spinal cord and retina, Poss and colleagues are focusing their attention on the heart and fins. Other vertebrates, such as salamanders and newts, can regenerate amputated limbs and tails, but when it comes to hearts, zebrafish appear to exhibit a more robust regenerative response.

In recognition of his contributions in deciphering zebrafish biology, the Pew Charitable Trusts this month named Poss as a Pew Scholar in the Biomedical Sciences. One of 15 scholars named in 2006, Poss will receive $240,000 over four years to further his research.

Since coming to Duke in 2003, Poss has established one of the largest zebrafish facilities in the country, with a capacity of more than 4,500 specialized tanks housing more than 50,000 fish. He also now mentors five postdoctoral fellows and two graduate students who are concentrating their efforts on better understanding the intriguing potential of zebrafish.

Based on the results of recent research, Poss is optimistic that future research ultimately will yield insights that will benefit humans with damaged hearts.

"In one set of experiments, we used very tiny scissors to remove about 20 percent of the ventricle, one of the fish's pumping chambers," Poss said. "We found that the incision site very quickly sealed itself with clots of red blood cells. Over the next two months, these clots are gradually replaced with new and functional heart muscle cells. The new heart tissue beat just like normal heart tissue."

The goal of the team's current research is to better understand exactly how the zebrafish are able to regenerate heart muscle. This involves detailed analysis of the dramatic cellular and biochemical changes that occur during the two-month period of new heart muscle growth.

His research into the zebrafish's ability to grow new fins may also lead to new insights into the role of progenitor cells.

"When we surgically remove a fin, the fish regenerates a perfect copy within two weeks." Poss said. "What makes this feat so impressive is that the fin is composed of many different tissue types, including bone, nerves, blood vessels, connective tissue and skin."

The use of zebrafish as a model for studying human disease has exploded over the past decade as growing numbers of researchers appreciate the fish's unique abilities, Poss said.

"Six years ago, our biennial meeting of zebrafish biologists had only two or three posters devoted to regeneration," Poss said. "At our June meeting, there were more than 1,000 attendees with approximately 50 abstracts related to regeneration."

Adding to the promise for zebrafish research, researchers will shortly complete the mapping of the fish's entire genome, Poss said. Having this genetic blueprint in hand, he said, should aid greatly in better understanding the genetics behind the zebrafish's regenerative properties.

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