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Scripps Florida Scientist Awarded $1 Million for Stress-Associated Disease and Aging Research

JUPITER, FL, April 20, 2012 – A scientist from the Florida campus of The Scripps Research Institute has been awarded just over $1 million from the National Institutes of Health to develop a range of new tests that could lead to new treatments for a number of stress-associated and degenerative disorders of advancing age.

Shuji Kishi, an assistant professor at Scripps Research, is the principal investigator for the three-year study.

The new tests will focus on diseases linked to oxidative stress (and the stress-induced inflammation that often accompanies it), closely associated with aging. Those diseases include atherosclerosis, Alzheimer’s and Parkinson’s disease, diabetes, heart attack, sarcopenia, liver and kidney disease, and stroke.

Despite the widespread damage caused by oxidative stress, the number of therapeutic remedies for it remains virtually non-existent.

During periods of cellular stress, such as exposure to UV radiation or chronic diseases like cancer, the level of highly reactive oxygen-containing molecules in cells can increase, resulting in misfolded proteins and cell damage. Cells can protect themselves from this damage by activating certain antioxidant genes, but age and extended periods of stress can impair that response.

In the new study, Kishi plans to develop a series of tests to identify drug leads that will prevent oxidative damage in a novel vertebrate model. His approach will involve high-content screens in zebrafish.

“The cell-based assays can be pursued using the ultra-high-throughput screening resources available at Scripps Florida, including a chemical library comprised of approximately 1 million compounds with structures that we know have properties suitable for drug development,” Kishi said.

Beyond the cell-based tests, Kishi plans to use newly developed transgenic zebrafish as a model organism for testing any drug candidates uncovered during cell-based screening. Those with potential after this round of testing will then be further evaluated to determine organ specificity and developmental toxicity, and for overall efficacy in preventing oxidative damage.

“We want to understand how these selected small molecules work in the zebrafish so that additional drugs can be designed based on the in vivo antioxidant response,” Kishi said.

Kishi’s laboratory is broadly focused on developing experimental models of aging and geriatric diseases, including neurodegenerative diseases.

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 about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates—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 www.scripps.edu.

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