Our laboratory develops and tests metabolic therapies, including calorie restriction, ketogenic diets and ketogenic agents for CNS oxygen toxicity (seizures), epilepsy, metabolic disorders, Alzheimer's disease, ALS, muscle wasting and cancer. To investigate the mechanism of these pathologies we use a variety of in vivo and in vitro techniques, including radio-telemetry (EEG, EMG), electrophysiology, fluorescence microscopy, confocal microscopy, atomic force microscopy (AFM), biochemical assays, in vivo bioluminescence imaging, behavioral testing and exercise performance. We have adapted many of these techniques for use inside hyperbaric chambers, which allows us to manipulate oxygen concentrations (from hypoxia to hyperbaric oxygen). Our current project is to identify physiological and cellular mechanisms of seizures and impaired brain metabolism. Our efforts have focused specifically on measuring brain EEG, neuronal excitability, reactive oxygen species (ROS) production and biomarkers of oxidative stress. Recently we have been interested in understanding the anticonvulsant and neuroprotective mechanism of the ketogenic diet, ketone esters and other ketogenic agents. Ketones reduce neuronal hyper-excitability, oxidative stress and enhances brain metabolism. Therapeutic ketosis can be used to treat a wide variety of neuropathologies linked pathophysiologically to metabolic dysregulation. Cancer is characterized by metabolic dysregulation and is responsive to metabolic therapies that lower blood glucose and elevate blood ketones. Cancer cells require glucose to survive and lack the ability to derive energy from ketones due to mitochondrial defects. Other areas of interest involve exploiting the anti-inflammatory and anticatabolic effects of metabolic therapies to prevent muscle wasting associated with aging, cancer and motorneuron diseases. In summary, our goal is to develop targeted metabolic therapies for a broad range of neurological disorders, metabolic disorders and cancer. Patents: http://www.freepatentsonline.com/WO2012154837A2.html