Cardiovascular Center Director Leiden Searches for Genetic Basis of Heart Disease
The Center for the Prevention of Cardiovascular Disease exists at the nexus of biology and public health. Center scientists are looking at the development of the heart and cardiovascular systems to pinpoint genetic components that lead to cardiovascular disease in later life. With this knowledge, they try to create ways to prevent or treat the disease in populations.
Jeffrey
Leiden is the Elkan R. Blout Professor of Biological Sciences and Director
of the Center for the Prevention of Cardiovascular Disease.
Dual interests in biology and public health are exemplified in Jeffrey Leiden, who arrived to direct the center last July. Leiden has been pursuing his interest in genetics since his high school days, and he believes that gene therapy holds the promise of preventing or curing cardiovascular disease. He is also a physician, who regularly leaves his research bench to spend time at the examination table. He will be practicing medicine at Brigham and Women's Hospital.
"Seeing patients is important to me for two reasons," said Leiden. "First of all, helping an individual improve his or her health is gratifying in a way that scientific research can never be. Secondly, treating patients provides a perspective on the disease that helps guide our research."
Treating people suffering from cardiovascular disease also serves as a constant reminder to Leiden of the pressing need for new ways to combat this disease.
Taking the approach that new treatment and prevention methods will result from understanding the genetic mechanisms that regulate cardiovascular development, Leiden has been busy identifying the roles of specific genes in this process. Over the last decade, his research group has cloned and characterized a number of critical regulators of cardiac, vascular, and T lymphocyte development.
Once a gene thought to have a role in cardiovascular development has been identified, Leiden's team uses mice to discover what that role is. Mouse cardiovascular systems operate similarly to humans, so the team breeds two strains of mice, one strain having an overabundance of the suspect gene, the other with that gene "knocked-out" of its chromosonal structure. Then the cardiovascular health of the mice in the two strains is monitored.
Leiden's group has developed a gene therapy that holds great promise for helping people who have balloon angioplasty to open an artery occluded by plaque.
Unfortunately, for about a quarter of the patients receiving this treatment, the artery soon begins to occlude again at the site of the angioplasty, requiring further invasive surgery. Leiden's gene therapy uses a cold gene that, in mice, successfully prevents the replugging of the artery. Human trials of the therapy are expected to begin in the near future.
Leiden holds an extraordinary respect for those who comprise his research team, a respect clearly returned. Indeed, all 15 members of his research team from the University of Chicago, where he had previously worked, moved with him to HSPH. "Our success is based on years of talented, dedicated people working together respectfully," he said. "Each member of our team is invested in the research and this is shown by our results."
One of Leiden's keys to success with his team lies in his support of lab personnel who choose to make a career of laboratory work, rather than using it as a necessary step towards an academic career. One of his colleagues, Hua Lin, a scientist who specializes in mouse pathology, has been with Leiden for a dozen years. Lin uses a complete set of miniaturized surgical tools to perform vascular surgery on mice.
Leiden came to HSPH because, he said, he had reached the stage of his career at the University of Chicago at which the next appropriate step would be up the administrative ladder to a deanship or directorship. Leiden considered his options carefully and decided that, at least for now, he preferred to stay closer to the science.
The school presented desirable opportunities for Leiden. "The school has the largest and best data sets of subjects who have provided genetic information," he said, referring to the many ongoing health studies like the Nurses' Health Study, the Health Professionals Study, and others. "These present extraordinarily rich opportunities for research."
In addition, he is also pleased by the opportunities here to work with a variety of departments within the school, and with other schools or hospitals in the area. "The fact that there are no boundaries for research is wonderful," he said, citing the attraction of working with colleagues from HMS, the Dana-Farber Cancer Institute, and Brigham and Women's Hospital.
The focus on cardiac development that Leiden brings to the center complements existing research by his colleague at the center, associate professor Guy Reed, who is investigating ways to prevent heart disease that is caused by blood clotting and atherosclerosis (occlusion of arteries in the heart).
The center was founded in 1992 by Edgar Haber who directed the center
until his death in 1997. Leiden's arrival reinvigorates the center, a
process that will be continued by the planned appointments of three additional
faculty members in the near future.
