Our research program focuses on gene environmental interactions related to complex diseases such as epilepsy, brain cancer, and neurodegenerative (the GM1 and GM2 gangliosidoses) diseases. We explore disease management using principles of metabolic control theory. This theory is based on the idea that compensatory brain metabolic pathways are capable of modifying the pathogenesis of complex diseases despite the continued presence of the genetic or environmental defects responsible for the disease. By shifting the brain metabolic environment, diet and drug therapies can potentially mask or neutralize molecular pathology. The diet therapies we use include caloric restriction, fasting, and the low carbohydrate, high fat, ketogenic diet. We also investigate the neurochemical and genetic mechanisms of inflammation, programmed cell death, and angiogenesis in mouse models of these diseases. The role of gangliosides and mitochondrial function are also studied. Our goal is to manage or control these complex diseases with novel therapies that have immediate translational benefit to the clinic.