Shuji Kishi, an assistant professor at Scripps Florida 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.
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.