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Scripps Florida Scientists Win $1.2 Million to Study New Strategies for Treating Obesity, Diabetes, Cardiovascular Disease and Muscle Decline

JUPITER, FL – February 3, 2016 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded nearly $1.2 million from the National Institutes of Health (NIH) to create a series of drug candidates that advance more effective treatments for a range of conditions, including obesity, type-2 diabetes, cardiovascular disease and muscle atrophy.

The three-year project will be led by Scripps Florida’s Associate Professor Theodore M. Kamenecka and Professor Patrick R. Griffin.

The team will focus on drug candidates that affect a family of medically important molecules known as nuclear receptors, which regulate gene expression in response to signals from various binding partners, including estrogen, progesterone, thyroid hormone and retinoic acid (vitamin A). First discovered in the 1960s, 48 nuclear receptors have been identified in humans.

However, a number of these receptors, called orphan receptors, have no known activator molecule or the identity of the activating molecule is controversial. Among these orphan receptors are estrogen-related receptors ERRα, ERRβ and ERRγ. These are the topic of the new research.

“While we’re looking at all three protein receptors,” Kamenecka said, “we want to focus on ERRγ because it’s closely associated with tissues such as heart, kidney, brain and skeletal muscles. Our goal is to optimize our current series of synthetic ERRγ activators for potency and selectivity to advance our ongoing study of the receptor’s role in various diseases.”

Previous research has shown that animal models genetically engineered to lack ERRγ exhibited decreased capacity for exercise and mitochondrial function in muscles compared to normal. In contrast, models with increased expression of ERRγ showed greater oxygen consumption, treadmill endurance and mitochondrial function and were resistant to diet-induced weight gain.

“Using the unique resources at Scripps Florida and the integration of chemistry and biology, we are confident we will develop selective activators (often referred to as modulators, as these molecules alter the gene program that nuclear receptors modulate). If we are successful, several Scripps Florida colleagues have expressed interest in using our ERRγ modulators to study muscle function and exercise capacity in the context of aging,” Griffin added. “We’re looking at a wide range of compounds to modulate this receptor’s activity in beneficial ways.”

The number of the grant, awarded by the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, is 1R01HD087046.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates and 20 members of the National Academy of Science, Engineering or Medicine—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see

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The new project will be led by Scripps Florida’s Associate Professor Theodore M. Kamenecka (left) and Professor Patrick R. Griffin. (High-res image)