Grant: Foundation Grant

Cancer is promoted by increased amounts of eIF4E, a protein that I discovered in 1978. The main role of eIF4E is to promote protein synthesis, which is a process that controls how much proteins are made, and is critical for cells to proliferate. It is now well established that eIF4E is present at high levels in many types of human cancer and may serve as a prognostic tumor marker. Moreover, eIF4E-binding proteins (4E-BPs) antagonize eIF4E activity, and act as tumor inhibitors. I, together with my research team, have not only discovered these proteins but have determined how they function and have defined their importance in many physiological and pathological conditions. Learning and memory is dependent on many of these proteins and mutant mice in which initiation of protein synthesis is enhanced demonstrate improvement in memory as compared to control mice. More recently, we discovered that eIF4E and 4E-BPs play important roles in causing an autism-like disease, and showed that by manipulating eIF4E activity we can reverse many abnormalities in mouse models of autism. We also demonstrated that eIF4E and 4E-BPs regulate circadian rhythms or an organism's "internal biological clock". The overarching research theme of my laboratory is the study of the mechanisms by which gene expression is controlled at the level of protein synthesis in health and disease. We will strive to discover drugs, in collaboration with pharmaceutical and biotechnology companies, to treat diseases that are caused by dysregulated protein synthesis including cancer, autism, Fragile X syndrome, and metabolic disorders.