DR. DOMINIC D'AGOSTINO
- 1994 - 1998: B.S. Nutritional Sciences and Biological Sciences, Rutgers University, New Brunswick, NJ
- 1999~2004 Ph.D. Neuroscience and Physiology; Division of Pulmonary and Critical Care Medicine; Graduate School of Biomedical Sciences; Rutgers University, Robert Wood Johnson Medical School, University of Medicine and Dentistry of NJ (UMDNJ), New Brunswick, NJ
- Doctoral Dissertation: “Heme oxygenase is necessary for hypoxic chemosensitivity of cultured rostral ventrolateral medulla neurons” September 3, 2004; UMDNJ-RWJMS (MEB) Mentor: Judith A. Neubauer, Ph.D.
Academic Employment and research experience
- 2004~2006: Postdoctoral Fellow (Mentor: Prof. Jay B. Dean) Department of Neuroscience, Cell Biology and Physiology) Wright State University Boonshoft School of Medicine, Dayton, OH
- 2006~2008: Postdoctoral Fellow Molecular Pharmacology and Physiology University of South Florida Morsani College of Medicine, Tampa FL
- 2008~2010: Research Assistant Professor (Non-Tenure Track) Molecular Pharmacology and Physiology University of South Florida Morsani College of Medicine, Tampa FL
- 2010~2015: Assistant Professor (Tenure Track) Molecular Pharmacology and Physiology University of South Florida Morsani College of Medicine, Tampa FL
- 2016~Present: Associate Professor (Tenured) Molecular Pharmacology and Physiology University of South Florida Morsani College of Medicine, Tampa FL
- 2014~Present: Visiting Research Scientist Florida Institute for Human and Machine Cognition (IHMC) Ocala, FL 34471
Summary of Research Program
Our laboratory develops and tests metabolic-based therapies, including calorie restricted diets, ketogenic diets, exogenous ketogenic agents and metabolic-based drugs that target specific pathways linked pathophysiologically with seizure disorders, neurodegenerative diseases, metabolic dysregulation, cancer, muscle wasting and exercise performance. 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), electron microscopy, histology, biochemical assays, metabolomics, toxicology, in vivo bioluminescence imaging, spectrophotometry, behavioral testing and motor function testing. Our work has adapted and utilized radio-telemetry, confocal microscopy and AFM for use inside environmental chambers. These tools allow us to conduct whole-animal, tissue and cellular studies under a broad range of oxygen concentrations and gas pressures to simulate extreme environments or cellular hypoxia/ischemia. Our past and current projects, supported by the Department of Defense (DoD) and Office of Naval Research (ONR), have identified cellular and molecular correlates of CNS oxygen toxicity (CNS-OT) seizures, a phenomenon which limits the capability of Special Operations (SpecOps) diving. Our efforts have focused specifically on measuring neuronal excitability, reactive oxygen species (ROS) production, biomarkers of oxidative stress and global blood and tissue metabolomics.
In 2009 we became interested in understanding the anticonvulsant and neuroprotective mechanism of nutritional ketosis and developed exogenous ketones that produce therapeutic levels of blood ketone. Therapies developed and tested include naturally-derived and synthetic agents that induce hyperketonemia independent of calorie restriction or carbohydrate restriction. The ketogenic diet is the standard of care for drug-resistant and refractory seizures resulting from a variety of etiologies. The brain’s ability to use exogenous ketone bodies for fuel has not been exploited therapeutically, and evidence suggests that therapeutic ketosis confers protection against seizures, hypoglycemia and neurodegenerative disorders by numerous mechanisms, including supporting brain energy metabolism. In addition to neurological disorders, metabolic-based therapies can target cancer metabolism, which derives energy primarily from glycolysis and substrate level phosphorylation. Due to mitochondrial defects, most cancer cells lack the metabolic flexibility to generate ATP from ketones. Our goal is to develop and test therapies that exploit the metabolic defects of cancer by targeting cancer-specific glycolytic metabolism (e.g. Warburg effect) and develop “press pulse” protocols enhance the efficacy existing cancer therapies. Independent of energy metabolism, our more recent work has shown that the ketone β-hydroxybutyrate is an inhibitor of NOD-like receptor family pyrin domain-containing protein (NLRP3) inflammasome, which suppresses inflammation. An emerging area of interest for me is developing metabolic-based therapies that improve health biomarkers linked to obesity, insulin resistance, type-2 diabetes, wound healing and exercise performance and resilience. Our in vitro and in vivostudies continue to validate the efficacy, mechanism of action and safety of metabolic therapies (diet supplements, drugs), including exogenous ketones, with pharmacokinetic and toxicology studies. Our data has produced remarkable results in animal models of seizures and cancer, and current efforts have focused on moving these metabolic-based therapies into human clinical trials.
Goal of Research
Dr. D'Agostino's research interest is to develop and test metabolic therapies that induce therapeutic ketosis for a broad range of neurological disorders and cancer. The most intense area of research in our laboratory is developing and testing ketone esters as a metabolic strategy to enhance brain function and prevent seizures. Another area of interest is exploiting the benefits of calorie restriction, ketogenic diets and ketone esters for prevention and treatment of cancer.
Highlight of Research
Our laboratory develops and tests metabolic therapies for CNS oxygen toxicity (seizures), epilepsy, neurodegenerative diseases, brain cancer and metastatic cancer. We investigate the mechanism of these pathologies with a variety of in vivo and in vitro techniques, including radio-telemetry (EEG, EMG, ECG), electrophysiology, fluorescence microscopy, confocal microscopy, atomic force microscopy (AFM), biochemical assays and in vivo bioluminescence imaging. Our current studies are focused on optimizing the anticonvulsant, neuroprotective and anticancer effects of the ketogenic diet and ketone esters.