Her colleagues call her "Dr. Z."

With a friendly, radiant smile and an easy manner, mirrored by those who work with her, she describes her laboratory as a place where people work hard but are happy enjoying adventure with science.

Lately for Dr. Zofia Zukowska and her team of researchers, there is much to smile about, due in great part to a recent award from the National Institutes of Health.

Zukowska, chair of the department of physiology and biophysics at the Medical Center, received this year's highly competitive MERIT Award from the NIH's National Heart, Lung and Blood Institute for her research on the sympathetic nervous system, which includes the effects of chronic stress on neuropeptide Y (NPY).

Her research focuses on effects of stress on atherosclerosis and metabolic syndrome; the latter being a collection of symptoms such as hypertension, abdominal obesity, glucose intolerance, undesirable blood lipid levels, as well as biomarkers associated with thrombosis and inflammation.

"Zofia's scientific contributions provide important insights into the biology of metabolic syndrome, and will undoubtedly have a significant impact on the linkage between obesity and stress," says Dr. Howard Federoff, executive vice president for health sciences.

The NIH recognizes researchers who have demonstrated superior competence and productivity in research with the MERIT (Method to Extend Research in Time) Award. MERIT Awards provide long-term support to investigators who show the best record of funding and scientific achievement in research areas of special importance or promise. Less than 5 percent of NIH-funded investigators are selected to receive the award, which comes with funding for up to 10 years.

For Lydia Kuo (M'10), the opportunity work with her mentor on the NPY project was something she could not pass up. After graduating with her Ph.D., she returned to Georgetown for medical school.

"Dr. Z is a fountain of ideas, and I always enjoy talking to her about all the different possibilities in research and in life," Kuo says. "She has really shaped the way I think scientifically and has been an amazing mentor and a second mother to me."

Zukowska, who received her doctoral degrees in medicine and physiology from Warsaw Medical Academy in Poland, has worked at Georgetown for nearly 22 years. And she’s been studying the stress hormone, NPY, for most of her time at the university.

NPY is a peptide neurotransmitter found in the brain and autonomic nervous system. With its six different receptors, it plays a number of important physiological roles including regulating appetite, anxiety, blood pressure, atherosclerosis and angiogenesis.

Zukowska's investigation was born out of many separate observations she collected over decades. "I'm an M.D. by training," she says, "and I worked several years in a clinic that dealt with people with hypertension and metabolic syndrome. I noticed that the people in the States get fatter and fatter, often in the waist, and at the same time, their stress in life seems to be going up and up."

That's when she began to question whether obesity and stress are related through NPY, whose role in stress and some stress-related conditions she has established through her earlier work.

"I started putting all these dots together and said OK, maybe stress induces obesity by way of the nerves that go to the fat tissue in that particular region of the body," she says. "Neuropeptide Y stimulates blood vessel formation, which feeds tissue growth, and maybe that gives you increased fat deposits around the waist."

Though stress is still regarded as a "soft science," whose complexity appears to scare away many basic scientists, Zukowska says she always had a scientific appreciation of complex problems requiring integrative thinking, and that NPY continues to delight and intrigue her. The professor has made it her mission to win attention and respect for chronic stress as a major disease risk factor. To this end, she founded and directs Georgetown’s Stress Physiology and Research Center, which is devoted to studies of stress in health and diseases.  Several landmark publications from her center have already won Zukowska high recognition and have become the hot discussion topics among members of the scientific community and the larger public.

In a 2005 study published in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology, she provided the first well documented, experimental evidence in animals that stress can accelerate atherosclerosis and lead to vessel blockage, and that inhibiting NPY can prevent these stress-induced effects. The study showed that stress-induced amplification was more rapid than the effects of a fat-rich diet in promoting atherosclerosis. As Zukowska planned experiments that model human stress in rats and mice, she was keen to devise an unambiguous protocol, one that can withstand the scrutiny of peer review, but at the same time allow human environmental factors into the equation.

Dr. Stephen Baker, associate professor of plastic and reconstructive surgery, joined Zukowska's team after becoming intrigued by her discovery that NPY stimulates new vessel growth and has the potential of promoting fat graft survival.

Baker provided liposuction fat for the mice in the latest NPY study, which looked at the effect of stress and diet rich in fat and sugar on development of obesity in mice.

"Zofia has these, what I call 'couch potato mice,' that are like Americans. They're not very active. [They have] a high-fat diet. ... they're stressed and they get obese. They develop diabetes, high blood pressure. Their abdomens fill with fat. It looks exactly the same as metabolic syndrome in humans," says Baker. "When we give them three months of daily injections into their belly fat of the antagonist to NPY their high blood pressure and diabetes go away. All the intra-abdominal fat goes away. I mean, it literally just dissolves away. So there are very profound implications. If that ever could be translated to humans, that’s Nobel Prize potential. It’s of that much significance."

Baker, Kuo and Zukowska are listed as inventors on the patent application for the technology used in the NPY study along with the Medical Center's Edward Lee and Michael Johnson, assistant professor at Lombardi Comprehensive Cancer Center.

Zukowska, a senior author of the study published in the July 2007 issue of Nature Medicine, is full of praise for her team. She says, "If one person from that group had not been available, we couldn't do the job, couldn't do it the best that they could. The success of the project would not have been possible."

When her groundbreaking article ran in Nature Medicine, the topic became front-page news across the country and around the world. Whether in mainstream or health and science media, obesity remains a hot topic.

Google "obesity" and one of the first hits is the link to a map on the Centers for Disease Control and Prevention Web site illustrating the growing prevalence of obesity in the United States. That's because about 64 percent of Americans are now overweight and more than 30 percent are obese, according to the CDC.

"As I have been working with my faculty members designing a new strategic plan, research for the next 10 to 20 years, trying to figure out what are the biggest challenges in medicine and health ahead of us," says Zukowska, "I see great potential in focusing on something that is so timely, so prevalent and so important, and those are the diseases of stress and of metabolism. If we are right, NPY may turn out to be a master stress neurohormone coordinating many of the essential processes underlying these diseases.  Thus, following this molecule could lead us to discover pieces of one of the biggest mysteries of the Western world -- the growing epidemics of obesity and metabolic syndrome."

Source: Blue & Gray