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Zeldin Labs Move toward Bench-to-Bedside Goal

By Blondell Peterson
September 2005

Darryl Zeldin
Darryl Zeldin (Photo by Blondell Peterson)

snapshot of the Asthmas Research web page
(Photo by Blondell Peterson)

Research efforts in the Molecular and Cellular Biology and Environmental Cardiopulmonary Disease groups are rapidly moving toward the bench-to-bedside goal according to translational investigator, Darryl Zeldin, who heads both groups at NIEHS.

"Our goal is to do mechanistic basic research, but we always try to think about how we can apply what we learn to humans to better understand human disease," said Zeldin, a senior scientist.

He went on to say that the goal of the clinical program is to try to develop novel ways of thinking about treatment and prevention by understanding basic concepts. "We're constantly trying to go from the lab bench to the bedside. We make basic observations in cellular systems or animal models, and then apply what we have learned to develop new ways to treat or prevent disease," he said.

Zeldin said sometimes scientists work the other way around as well, and start with the patient. "We often take patient samples back to the lab to analyze them in an attempt to understand disease pathogenesis," he said. "So we constantly go from bench to bedside and back to bench."

Zeldin wears the hat of a clinical researcher and a physician. He is on staff at Duke University Medical Center and sees patients two months out of the year in intensive care or on the consult service. Working primarily at the Veterans Administration Health Center, he heads a team of residents, interns, medical students and fellows. Modestly, he claims, "They do all the work. I get to come in every morning and make sure they are doing a good job and pat them on the back."

Zeldin said most of his clinical time is spent talking to families and focusing on the big picture, letting his team deal with the details. By noon each day, he is back in the lab at NIEHS. "My lab doesn't shut down when I go to the clinic," he said.

Zeldin's largest study so far is the multimillion dollar asthma study. Recruiting and enrollment started in January and will last until 2008. Labs are analyzing dust samples and blood antibodies while the Centers for Disease Control administers the questionnaire from mobile trailers across the country. The data generated will be released in 2-year blocks. For more information on this study, visit Zeldin's asthma research website is located at https://www.niehs.nih.gov/airborne/

"We're working closely with Stephanie London in the epidemiology branch to incorporate a genetic component to this study," he said. "We hope to get DNA from a significant number of these individuals so that we can look at asthma and allergy genes and how that relates to the exposures and disease outcomes," he said. "It's a resource we're creating here, not just for ourselves, but for other scientists."

According to Zeldin, research that began 12 years ago to understand the role of certain types of fatty acids in cardiovascular disease has moved toward the clinical component. "We've now identified polymorphisms or variations in the human gene and shown that they are functionally important," he said. "More recently we have shown that these polymorphisms may be risk factors for heart disease and stroke."

Zeldin's group will release two papers in the next few months that will show relationships between polymorphisms and the genes in this particular pathway and cardiovascular disease risks. "These genes are turning out to be heart susceptibility genes," he said.

"That project is a good example of something that started here at NIEHS," Zeldin said. "We worked on cells, cloned genes and developed transgenic animal models to determine the functional importance of those genes. Only more recently have we been able to translate what we did to human studies where we can look at the association between variation in these particular genes and cardiovascular disease risk. Our long term goal is to use this information to develop novel therapies for heart disease."



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