Lee Receives Two Prestigious Research Awards from NIH

June 6, 2023

IIT-affiliated faculty member, Dr. Kin Sing Lee, recently received two prestigious research awards from the National Institutes of Health. A Maximizing Investigators’ Research Award (MIRA) R35 from the National Institute of General Medical Sciences (NIGMS) was awarded in the amount of $1.9 million for his project, “Ferroptosis and Polyunsaturated Fatty Acid Metabolism." The second award, an R01 granted by the National Institute on Aging (NIA) will supply $3.1 million for Lee’s project, "Development of soluble epoxide hydrolase inhibitors for the treatment of Alzheimer's disease."

The NIGMS MIRA R35 project will investigate the fundamental mechanism of how polyunsaturated fatty acid metabolism regulates ferroptosis, a new programmed cell death pathway, in a cell-type-specific manner. Lee and his research team will apply a multidisciplinary approach by combining synthetic probes, a novel animal model named C. elegans, and various genetics techniques to dissect the mechanism and identify potential receptors for regulating ferroptosis. Their findings will improve our understanding of how dietary lipids regulate this novel programmed cell death pathway, which then affects human health. “We are so excited to be supported by NIGMS MIRA (R35) to investigate the molecular interactions between lipid metabolites and this cell death pathway,” commented Lee. “Hopefully, we can improve our understanding of how diet affects human health.” 

The overall goal of the NIA R01 project is to develop novel soluble epoxide hydrolase inhibitors with improved drug-like properties and brain exposure to treat or prevent Alzheimer’s disease. Soluble epoxide hydrolase is an enzyme that degrades largely beneficial endogenous epoxy fatty acids to less active or pro-inflammatory dihydroxy fatty acids. Lee’s research team comprises experts in drug design, medicinal chemistry, sEH biochemistry, protein modeling, pharmacokinetics, Alzheimer’s disease pathology, and vascular biology that will work together to apply a design-test-learn strategy to guide the design of the next generation of inhibitors. By the end of the project, Lee and his team hope to have identified a novel drug candidate ready for preclinical testing. “Drug discovery is a team sport,” Lee acknowledged. “I am honored to be leading a team of excellent scientists from MSU to develop new candidates for the treatment of Alzheimer’s disease. Hopefully, we can also apply the developed candidate for other neurodegenerative diseases in the future.” 

The overall goal of Lee’s laboratory is to investigate how dietary lipids affect human health with a focus on neurodegeneration and aging through their downstream metabolism. They use chemical biology, state-of-the-art instrumentation, novel model organisms, and genetics tools to investigate the mechanism of how lipid metabolites affect disease pathology and identify corresponding receptors. The knowledge they will acquire from their research will improve our understanding of how environmental exposure including diet, toxic chemicals, etc. affects human health by modulating lipid metabolites.