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New heart failure trigger could change the way cardiovascular drugs are made

by Heather Buschman, Ph.D. on July 18, 2012 at 10:01 am | 1 comment
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APJ’s yin-yang role in cardiac function: the receptor APJ serves a dual function in heart health, depending on how it’s activated. While APJ enhances heart health upon binding the hormone apelin (green), APJ can also trigger heart enlargement and failure when it senses certain mechanical changes (red).

APJ’s yin-yang role in cardiac function: the receptor APJ serves a dual function in heart health, depending on how it’s activated. While APJ enhances heart health upon binding the hormone apelin (green), APJ can also trigger heart enlargement and failure when it senses certain mechanical changes (red).

In their quest to treat cardiovascular disease, researchers and pharmaceutical companies have long been interested in developing new medicines that activate a heart protein called APJ. But researchers at Sanford-Burnham Medical Research Institute and the Stanford University School of Medicine have now uncovered a second, previously unknown, function for APJ—it senses mechanical changes when the heart is in danger and sets the body on a course toward heart failure. This means that activating APJ could actually be harmful in some cases—potentially eye-opening information for some heart drug makers. The study appears July 18 in Nature.

“Just finding a molecule that activates APJ is not enough. What’s important to heart failure is not if this receptor is ‘on’ or ‘off,’ but the way it’s activated,” said Pilar Ruiz-Lozano, Ph.D., who led the study. Ruiz-Lozano, formerly assistant professor at Sanford-Burnham, is now associate professor of pediatrics in the Stanford University School of Medicine and adjunct faculty member at Sanford-Burnham.

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Another way kickboxing is good for the heart

by Heather Buschman, Ph.D. on November 4, 2010 at 11:16 am | 2 Comments
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Dr. Barbara Ranscht is a neuroscientist. While studying brain development and cancer for more than 20 years, she has come to know a molecule called T-cadherin. This protein is anchored to the cell membrane, where it senses changes in the extracellular environment to ultimately regulate cellular motility and growth. T-cadherin has multiple functions in the nervous system, but when she first discovered this protein in the 1990s, Dr. Ranscht also noted its abundance in the heart. For many years Dr. Ranscht paid little attention to the molecular workings of the heart, preferring to stick to the mysteries of the brain. Until recently, when she came across new clues about T-cadherin and its possible role in protecting the heart from stress-induced damage. At that point, most researchers would probably have let go of the idea rather than jump into a new field.

Luckily, Dr. Ranscht goes kickboxing with her colleague, friend and heart expert, Dr. Pilar Ruiz-Lozano.

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Heart team gets pumped up

by Heather Buschman, Ph.D. on September 28, 2010 at 8:21 am | 0 Comments
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A collaborative team led by Dr. Gabriel Haddad at the University of California, San Diego (UCSD), which includes Sanford-Burnham’s Dr. Rolf Bodmer, Dr. Pilar Ruiz-Lozano, Dr. Karen Ocorr and Dr. Giovanni Paternostro, was awarded a $10 million grant from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. The team will research the molecular response to low oxygen levels – a condition known as hypoxia– in heart, lung and brain cells.

“This funding will allow us to develop powerful predictions of how the human heart and other organs can be protected from hypoxia-inflicted injury by studying both fruit flies, which are very tolerant to low oxygen, and mice, which are less tolerant,” explains Dr. Bodmer, professor and director of Sanford-Burnham’s Development and Aging Program.

According to Dr. Paternostro, adjunct assistant professor, ”This grant will allow us to continue our work on the systems biology and metabolomics of hypoxia, an ongoing collaboration with Dr. Haddad and with the other scientists participating in the funded project.”

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