New Wall Center research director focuses equally on research, patient care

By KRISTA CONGER

"Bench-to-bedside" usually refers to the translation of basic research into medical treatments that directly help patients. But the phrase works equally well to describe a typical day for cardiologist and researcher Marlene Rabinovitch, MD.

Rabinovitch, the new director of cardiovascular research at the Vera Moulton Wall Center for Pulmonary Vascular Disease, divides her time between caring for patients and researching the causes and potential new treatments for cardiovascular disease, pulmonary hypertension and related disorders. She will present the results of her research and other advances in vascular biology in a plenary lecture at the annual scientific meeting of the American Heart Association next week in Chicago.

"I really believe that there will soon be new options for treating patients with pulmonary hypertension," said Rabinovitch, professor of pediatrics and, by courtesy, of developmental biology at the School of Medicine. "The hope is that we may also find treatments for systemic hypertension, coronary artery disease and possibly even cancer." The lecture reflects her 2002 Paul Dudley White International Lectureship award, given to honor a non-U.S. physician scientist who has made a major contribution to cardiovascular research.

Rabinovitch and her husband, neonatologist Richard Bland, came to Stanford and Packard Children’s Hospital in July. Previously Rabinovitch was the director of cardiovascular research at Toronto’s Hospital for Sick Children and Bland was the director of lung biology at the University of Utah.

Rabinovitch’s research focuses on understanding how high blood pressure or injury damages blood vessel walls. She’s found that one step of the process — the release of a substance called elastase — is very harmful. By reducing vessel flexibility, elastase is responsible for much of the damage done in coronary artery disease, including the thickening and stiffening of vessel walls, which leads to blockages.

"One of the most exciting aspects of our work is that we’ve shown that elastase inhibitors can not only prevent but also reverse disease progression in animal models of vascular diseases," said Rabinovitch. "We may one day be able to use a similar approach to treat not only pulmonary hypertension but also restenosis, atherosclerosis, and post-cardiac transplant coronary artery disease and rejection."

Rabinovitch and her team are now working on ways to deliver treatment such as the elastase inhibitor to the damaged vessels. "We’ve identified several small peptides that have different predilections for specific types of blood vessels," says Rabinovitch. "We’ve fused them with potential therapeutic genes and are now testing whether these new molecules will home to the target organ."

The team has had some success with a system that expresses the prostaglandin gene in the blood vessels. Physicians use prostaglandin to artificially keep open a naturally occurring passageway between vessels near the heart that usually closes shortly after birth. However, some infants born with severe heart defects will die if the channel closes before surgery can be attempted. Expressing prostaglandin where it’s needed — in the blood vessels — may one day allow physicians to bypass the toxic effects that occur when it’s given intravenously. These effects include low blood pressure and impaired bone growth.

Rabinovitch is also investigating the genetic basis of pulmonary vascular disease and searching for novel genes that cause high blood pressure. She is collaborating with Stanford investigators with expertise in gene arrays, drug discovery and biotechnology development to answer these and other questions.

Unlike strictly academic researchers, Rabinovitch sees the human cost of these biological missteps on a regular basis. "We have patients come to the Wall Center from all over the world, with complex abnormalities related to blood vessel development and growth in the lung," she says. "The many interdisciplinary collaborations fostered by Packard provide a unique vehicle for applying novel discoveries directly to patient treatment and diagnosis and have inspired us with a new surge of energy and enthusiasm."

Stanford receives $31.8 million to establish Center for Pulmonary Vascular Disease (7/6/00)

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