The National Institute of General Medical Sciences recently awarded $1.23 million to Ronald “Nick” Laribee, PhD, associate professor in the department of Pathology and Laboratory Medicine in the College of Medicine at the University of Tennessee Health Science Center (UTHSC). Dr. Laribee is the lead investigator on a project to determine how the epigenome receives crucial nutrient information to promote cell growth, proliferation, and survival. Daniel Johnson, PhD, director of the UTHSC Molecular Bioinformatics Core, is co-investigator on the project.
The ability of cells to sense and respond to nutrients profoundly affects an individual’s health. Nutrient availability controls all aspects of cellular function including when to grow, when to divide, and what genes to turn on or off. The cellular machinery that signals nutrient flux and controls cellular response to nutrient availability is essential, but remains poorly defined.
Dr. Laribee’s study focuses on mTORC1, a key protein complex that senses nutrient levels and controls protein synthesis. Its signaling pathway is dysregulated in virtually all cancers and many neurodevelopmental disorders. One aspect of the mTORC1 pathway that remains almost completely unknown is how it regulates gene expression within the context of chromatin, the protein/DNA complex that forms chromosomes. Dr. Laribee’s team will examine the process biochemically using baker’s yeast as a genetic model, since yeast and human mTORC1 signaling are highly similar. The aim is to determine how mTORC1 regulates the epigenome to better understand how its corruption causes cancer and neurodevelopmental disorders.
“Since mTORC1 is deregulated in almost all cancers, understanding these biochemical mechanisms will identify novel targets for anticancer drug development,” Dr. Laribee said. “Because mTORC1 dysfunction also impairs neurodevelopment, these studies will identify mTORC1-regulated epigenetic pathways that could be new therapeutic targets for treating many of these neurodevelopmental disorders.”