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News / 01.3.06

Sekar Kathiresan receives prestigious award to pursue genetic causes of heart disease

By Michelle Nhuch, Communications
Sekar Kathiresan, MD
Sekar Kathiresan, MDCourtesy of Broad Communications

Sekar Kathiresan, MD, received a Doris Duke Clinical Scientist Development Award for research at the Broad Institute toward discovering the genetic causes of cardiovascular disease. Kathiresan, a cardiologist at Massachusetts General Hospital, is one of eleven researchers recently selected by the charitable foundation, which helps young physician-scientists make the challenging transition to an independent research career.

"Dr. Kathiresan is a young investigator who has received rigorous training in cardiology, epidemiology and genetics, and who has access to both state-of-the-art genomic technologies and outstanding clinical samples," said Joel Hirschhorn, assistant professor of genetics at Harvard Medical School, associate member of the Broad Institute, and a coordinator of the Broad Institute's Metabolism Initiative. "As such, he is perfectly positioned to make exciting new discoveries about the genetic contributors to cardiovascular disease in the population." Hirschhorn, along with Chris O'Donnell, assistant professor of medicine at Harvard Medical School, associate director of the Framingham Heart Study, and associate member of the Broad Institute, mentored Kathiresan at the Broad and MGH.

Cardiovascular disease is the leading cause of death for both men and women in the United States and has been for more than two generations. The disease itself involves a variety of conditions that are harmful to both the heart and blood vessels. Research shows there is a strong genetic component, thus if you are related to someone who has the disease you are more likely to inherit the devastating condition. Although early detection and treatment is available, a heart attack frequently is this silent killer's first warning.

Like many common diseases, cardiovascular disease involves an interplay between genes and environmental factors. Finding the genes that underlie these kinds of diseases can take many years, exhausting both financial and intellectual resources. Newly available genomic tools, such as the HapMap – a catalog of common genetic information across the entire genome – provide researchers like Kathiresan with a genetic compass for navigating regions in human DNA that may be tied to disease.

Kathiresan and his colleagues will explore a novel biologic pathway that may be involved in the development of cardiovascular disease. Previous studies in mice and human cells suggest that two proteins, RANKL and osteoprotegerin (OPG), work as the yin and yang in maintaining blood vessel integrity. Mice engineered to lack OPG develop calcification of the arteries, suggesting that OPG protects the blood vessels from this problem. However, the relevance of this pathway to human heart disease still needs to be established.

By testing blood samples from diseased and healthy patients in several clinical studies, including the Framingham Heart Study, the researchers will determine whether the OPG pathway is involved in human heart disease and whether genetic variation in this pathway is linked with disease.

If the team demonstrates that the OPG pathway proteins and/or genetic variants are associated with cardiovascular disease, it will create new targets for diagnostics and therapies. And, because OPG pathway proteins have already been determined to play a role in osteoporosis, therapies targeting this disease have been developed and can be immediately tested for efficacy in cardiovascular disease.

"Thanks to Doris Duke funding, we now have a very talented physician investigator, Dr. Sek Kathiresan, able to pursue this novel and potentially important pathway for cardiovascular disease," said O'Donnell. "The opportunities are greater now than ever before for Dr. Kathiresan to expand the boundaries of our knowledge for the prevention and treatment of cardiovascular disease using information from the Human Genome Project and the latest developments in imaging technologies in the Framingham Heart Study."

Doris Duke Clinical Scientist Development Award

The Doris Duke Charitable Foundation has awarded 82 Clinical Scientist Development Awards since 1998, totaling approximately $39 million. The award program supports junior physician-scientists making the critical transition to an independent clinical research career. Each researcher selected for this award will receive $135,000 per year for 3 years. To learn more about the Foundation's medical research programs, visit www.ddcf.org/mrp.