Dr. Aimee Eggler
Department of Chemistry
College of Liberal Arts & Sciences
Project Title: Bridging the Gap Toward Implementing Synergistic Nrf2 Activators in Chronic Disease Prevention
Eighty-six percent of the United States’ health care costs are devoted to treatment of chronic diseases, most prominently cancer, heart disease, diabetes, and chronic obstructive pulmonary diseases. Notably, emerging evidence indicates that chronic diseases can be prevented or mitigated by activating the Nrf2 protein within our bodies. Nrf2 turns on genes that encode antioxidants and other protective proteins, combating stressors that contribute to chronic disease progression. Nrf2 is activated by various stresses, as well as by an extensive list of small molecules. Remarkably, many of these are found in foods or traditional medicines from plants, such as the molecule sulforaphane from broccoli sprouts, in over 60 clinical trials. An exciting, emerging area of research is combining two or more Nrf2 activators to achieve an effect that is more than additive, termed synergistic. Our research group has developed a two-molecule model system of synergistic Nrf2 activation, combining sulforaphane with the molecule di-tert-butylhydroquinone (dtBHQ). The significant extent of synergism observed provides a tractable means of investigating the mechanisms of synergy. We have developed a mathematical model to quantitate synergism of Nrf2 activators using the sulforaphane/dtBHQ combination. The funding provided by the University Summer Grant Program will support two key next steps. First, because dtBHQ is not FDA-approved, we will screen for synergism between sulforaphane and other molecules that are from natural sources and/or FDA-approved for use by humans. Second, to investigate how synergism occurs, we will develop assays to probe the molecular changes within the cell upon treatment with the two molecules.