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David Gozal's résumé says he is a pediatric pulmonologist, a molecular biologist and a physiologist. It says he is a professor of pharmacology and toxicology. And it says he is a former officer in the Israel Defense Forces Medical Corps.

But nowhere does his résumé say what the UofL researcher really is -- a builder.

As a young physician in 1986, Gozal established Israel's first clinic to study and treat children with sleep disorders, launching a distinguished career as one of the world's leading experts in the newly emerging discipline.

Two years later, after completing his chief residency in Haifa, Israel, Gozal traveled as a representative of the Israeli government to the West African nation of Cameroon to help the struggling republic establish a functional system of rural health-care delivery, earning a knighthood in the process.

And in 1991 Gozal undertook pioneering research at UCLA to developed new functional brain-imaging techniques, allowing researchers to discover for the first time that multiple areas of the brain were involved in the body's response to breathing disorders like asthma, Sudden Infant Death Syndrome and sleep apnea.

Before joining UofL's School of Medicine in 1999 as director of the newly formed Division of Pediatric Sleep Medicine, Gozal built an innovative cross-disciplinary research program at Tulane University that quickly became a leader in studying the body's molecular response to sleep disorders. His Tulane team also began linking basic research to real-world results, demonstrating in landmark research that children with sleep apnea also have significant learning deficits and behavioral problems.

"I like to build new programs," Gozal says with typical understatement. "It's very rewarding to start from scratch and build something into a successful reality."

Now he's taken on what may be the biggest construction project of his career: creating and shepherding the growth of a pediatric sleep program and the Kosair Children's Hospital Research Institute at the University of Louisville.

In just 2 1/2 years, Gozal has established one of the country's top pediatric sleep clinical programs (the Kosair Children's Hospital Sleep Medicine and Apnea Center), hired nine highly regarded scientists and grown the new institute's research budget to about $4 million annually, primarily through federal grants.

"Dr. Gozal's success has far exceeded my expectations," says Larry Cook, M.D., chairman of the pediatrics department at UofL. "I would never have dreamed that we would come so far, so fast. Growth in the research enterprise has been astronomical in terms of incremental dollars in the pediatric research institute and the acquisition of additional funded and non-funded faculty."

But Gozal, who holds the Children's Hospital Foundation Chair for Pediatric Research, is only getting warmed up.

"We're like a small child," he says of the research program, using an age-appropriate analogy. "The first step is done and we've just begun walking. But there is a long road ahead of us. We're not running yet."

Fertile ground

Gozal says he was drawn to Louisville for a variety of factors, including the city's first-rate Kosair Children's Hospital, UofL's excellent cross-disciplinary research facilities and, of course, the challenge of building a new research institute from the ground up.

Equally important was the fact that Gozal would have relatively exclusive access to a large group of school-age children -- a mandatory prerequisite for undertaking the large-scale epidemiologic studies needed to further understand apnea's affects on learning and behavior.

"I needed a city of a certain size that had a good hospital with good recognition in the community, that would be virgin from the standpoint of not having a pediatric sleep center so I could recruit the people I needed, and that would allow me to accomplish the basic science I wanted to do," Gozal explains.

"You start putting it all together, and Louisville had everything I needed to develop what I call my 'cell-to-child' approach. This allows us to study all aspects of sleep disorders, from the molecular level all the way up to clinical care and epidemiology.

"Louisville is turning out to be a very fertile ground to address these issues, so we can try to find some answers that will be applicable to the whole world."

Gozal arrived at UofL with a $1 million grant from the National Institutes of Health to study neurocognitive functioning in children, and he wasted no time getting to work. Although many of his findings have yet to be published -- Gozal expects them to appear in a major journal within six months -- his team's study of thousands of local school children identified long-term learning deficits and hyperactivity among those who snore and, thus, may suffer from disrupted sleep.

"We're dealing with a major epidemic of disease that people don't recognize," Gozal says. "People think snoring is funny. And it's not funny. It leads to major consequences -- lower intelligence and self-esteem, reduced ability to function on a daily basis, cardiovascular consequences, hypertension, strokes, heart attacks. All this is brought about by sleep-disordered breathing."

Sleep apnea affects about 5 percent of the adult population and 2 percent of children. In children, sleep apnea primarily is caused by large tonsils or adenoids that block a child's airway during sleep.

"Snoring is the major symptom," Gozal says, "but sleep apnea also causes the body's level of oxygen to decline during sleep. When that happens, a child awakens, takes a breath and goes back to sleep."

Gozal says the cycle, which the child never realizes is happening, can occur up to 700 times a night and leaves its victim feeling "very fatigued."

Now Gozal and his researchers, armed with a $900,000 grant from the U.S. Department of Education, are examining whether early intervention -- removing the tonsils or adenoids of affected preschoolers -- can eradicate learning deficits.

"Our preliminary findings show that the affect can be corrected, at least in part, and there is some recovery," says Gozal, who continues to treat sleep-disordered children in the Kosair clinic each week despite a grueling research agenda.

"But the major question is: Can we identify when we need to intervene, and how quickly, to prevent the long-term consequences we have demonstrated?

"If the diagnosis is too late, your child will lose a substantial number of IQ points no matter what you do."

At the same time, researchers must be mindful of the dangers posed by surgery, especially on young children.

"There is morbidity with surgery, and there is mortality with surgery," Gozal notes. "So we need to define exactly the cost-benefit ratio of when to intervene. We need to know when the process of snoring is causing damage and when it's not."

The potential benefits of treatment are, of course, tremendous.

"If a child has an IQ of 200 and loses 10 points, which is what our models allow for estimation of IQ loss, you would never know it. But if a child has an IQ of 100, which is the average of the population, a loss of 10 points can mean the difference between going to college or not. And that's very important."

Basic research

While Gozal's team continues to examine the clinical aspects of sleep apnea, they also are conducting basic research into its molecular and physiological aspects, thanks to more than $2 million in grants from the NIH and the American Heart Association.

By exposing rodents to low levels of oxygen or waking them periodically as they sleep, Gozal's team has been able to recreate in animal models the consequences of sleep-disordered breathing. The result is hyperactive, aggressive rats and mice that have difficulty learning new tasks and can't pay attention.

"Not only do these animal models allow us to mimic, in a very controlled condition, the physiological and behavioral elements we've been interested in, but they also allow us to study tissue samples and analyze changes that are happening to organs, both at the gene level and the protein level," Gozal says.

"These models have been published in the most prestigious journals, like Nature and the Journal of Neuroscience, and we're recognized as one of the few centers in the world that can do this."

The institute's neurobiologists also are developing cellular models that allow them to study hypoxia-induced molecular changes directly in cells, bypassing animal models completely.

One of the immediate goals of this research is to identify and study areas of the brain that are either more or less susceptible to damage caused by low oxygen levels.

"We are looking at differences in those areas to determine what kinds of proteins and genes they will recruit," Gozal says.

"We've also identified potential candidates for introducing vulnerability and potential candidates for providing tolerance to this damage.

Ultimately, such discoveries could lead to the development of new drugs or therapies that protect the brain from the damage caused by sleep apnea without requiring surgical intervention.

"This would be very important," Gozal says. "Not only could we treat the disease earlier, but we could avoid surgery, which is not a panacea -- especially in adults, who often need life-long treatment with machines that help them breathe through the night.

"This is all ongoing work that has put us at the forefront of pediatric sleep research in the world," Gozal notes.

"There is no doubt in my mind that new technologies currently available at UofL, such as proteomics and functional genomics, will allow us to further accelerate our research pace and bring respite to our patients sooner."

Growing the program

The current success of the research institute and sleep clinic is only just the beginning for Gozal, who has made a career out of pushing the boundaries of medical understanding.

To ensure further growth, he's helping develop an ambitious plan to expand pediatric research and clinical care at UofL. Gozal's initial blueprints call for the creation of endowed chairs in pediatric medical and surgical research, the expansion of clinical faculty, and the enlargement of UofL's residency and fellowship programs.

To date, Gozal's programs have received $6 million in endowed funding - $4 million from the Children's Hospital Foundation and the Commonwealth of Kentucky to establish endowed faculty positions, including Gozal's own; and $2 million to fund ongoing operations at the institute.

But UofL's neighbors have substantially more cash in their pediatric endowment coffers, Gozal notes. Riley Children's Hospital in Indianapolis has a $400 million research endowment, while Cincinnati Children's Hospital Medical Center has more than $1.2 billion in its endowment and Vanderbilt Children's Hospital has $450 million.

"Per-dollar endowment, UofL probably has the most competitive pediatric research program in the United States," Gozal says. "But obviously, the only way to attract more investigators and to start developing new areas of interest is by increasing the endowment and allowing for a critical mass of researchers to form and technological resources to be generated."

The Kosair Children's Hospital Research Institute currently is developing a research program in pediatric diabetes under the guidance of Paul Epstein, Ph.D., who joined UofL last year to fill the Carol B. McFerran Endowed Chair in Pediatric Diabetes Research.

Other research programs in pediatric cancer, developmental biology and outcomes research are expected to follow as the institute's endowment grows, Gozal says.

The first contribution already has been committed by Norton Healthcare, which operates Kosair Children's Hospital: $4 million to fund new endowed chairs and $5 million to effectively double the institute's research space at UofL.

"We have a wonderful clinical facility and we have a significant amount of specialized and well-trained clinicians," says Gozal, who was recruited to UofL with a $1 million endowment from Norton and a matching $1 million gift from the state's Research Challenge Trust Fund, or "Bucks for Brains" program.

"But we need to bring more faculty to the research ranks, both in clinical and basic research, to become a leading force in pediatrics. I think we have that potential.

"Children are our future," Gozal adds earnestly. "I think that is a worthy investment.

For Gozal, the builder, few things would be more rewarding than to see UofL rise to the top of the pediatric research ranks.

It would, after all, mean the completion of another successful construction project. But more important, it would mean a better quality of life for the children of Kentuckiana -- and the world.

"We have discovered several pathways that appear very promising," he adds.