September 28, 2007

Davies lands NIH New Innovator award

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Sean Davies, Ph.D., is among the first group of scientists to receive the NIH Director's New Innovator Award. (photo by Neil Brake)

Davies lands NIH New Innovator award

Sean Davies, Ph.D., has a novel idea that could eliminate the daily drug intake required to treat chronic diseases. And now he has five years of funding from the National Institutes of Health to develop and test that idea.

Davies, research assistant professor of Pharmacology, is among the first group of scientists to receive the NIH Director's New Innovator Award. The program was launched to support new investigators with bold research proposals that could have great impact on biomedical or behavioral science.

“Novel ideas and new investigators are essential ingredients for scientific progress, and the creative scientists we recognize with (these awards) are well-positioned to make significant-and potentially transformative-discoveries in a variety of areas,” NIH Director Elias A. Zerhouni, M.D., said in a statement.

Davies is one of 29 awardees who will receive $1.5 million in direct costs over five years. More than 2,100 investigators applied for the awards.

“I was shocked; I'm still kind of pinching myself,” Davies said. “I'm also really excited to get going on the project.”

Davies proposed using probiotic bacteria-“friendly” bacteria like those in yogurt — to deliver a constant stream of drugs to patients with chronic illnesses.

The idea, he said, is to genetically engineer bacteria to become drug-producing factories and introduce them into the stomach, where they can take up residence in the gastrointestinal tract and churn out the drug for a long period of time.

Our gastrointestinal tracts are already teeming with bacteria, so why not take advantage of molecular biology approaches to put some of our microbial friends to work, Davies said.

“We have this enormous genome that's in our guts, and that we know almost nothing about,” he said. “It occurred to me that if we can manipulate that genome, it would be like gene therapy for the gut.”

If it works, the system would allow one-time — or at least relatively few times — treatment of chronic medical conditions and offer a flexible, low-cost platform for new drug development.

Using mice as a model system, Davies will determine the optimal strains of probiotic bacteria for colonizing and persisting in the gastrointestinal tract and for expressing proteins. He will also develop methods for regulating protein expression levels and for eliminating the modified bacteria, but not the normal flora, from the gastrointestinal tract.

The first therapeutic compounds Davies will attempt to deliver are apoA-1 mimetics, peptides that remove cholesterol and oxidized lipids from cells and atherosclerotic plaques, and ACE inhibitors, peptides that lower blood pressure.

These two drugs represent a good starting point, he said, because there is evidence they will — with some modifications — cross the gastrointestinal lining, a challenge for peptides or proteins produced in the stomach.

Davies will test the delivery and therapeutic impact of these cardiovascular drugs in mice that are obese and have high blood pressure, high cholesterol and atherosclerosis.

Davies praised the NIH for offering the new program.

“I think the notion of putting some money toward high-risk but potentially very high-yield projects is wonderful.”

Davies earned his Ph.D. in Experimental Pathology from the University of Utah in 1999. He came to Vanderbilt as a postdoctoral fellow with L. Jackson Roberts, M.D., and has focused on the role of peroxidized lipids in driving the inflammatory responses related to vascular disease. He was promoted to research assistant professor in 2004.