Dr. Stacpoole’s laboratory and clinical research focuses on the causes and treatment on human intermediary metabolism and on the causes and treatment of acquired and congenital mitochondrial diseases. He developed a prototype, dichloroacetate (DCA), of a new class of cellular metabolic modulators that acts by targeting a key component of mitochondrial energy metabolism, the pyruvate dehydrogenase enzyme complex (PDC).
This work has been translated into clinical trials of DCA in children with congenital PDC deficiency and in adults with malignant brain tumors or pulmonary arterial hypertension, conditions in which the PDC is pathologically inhibited.
Dr. Stacpoole also collaborates with other UF researchers to investigate 1-carbon metabolism in healthy humans and in those with experimentally-induced deficiency of vitamins essential to this process.
Dr. Clare-Salzler, whose primary appointment is with the Department of Pathology, has a research program looking at immune mechanisms in autoimmune thyroid disease and Type I diabetes.
Metabolic Dysfunction in Obesity and Insulin Resistance
Dr. Sunny uses stable isotope based Mass Spectrometry and Nuclear Magnetic Resonance in combination with standard tools in molecular biology to profile glucose and mitochondrial protein and fat metabolism. Stable isotope based metabolic flux analysis and metabolomics help us derive functional information at the level of the metabolome. Functional information transmitted through the -omics cascade is inherent in the several shared metabolic networks. Metabolic flux analysis helps us to identify patterns of alterations pivotal to the development and progression of diseases like insulin resistance and diabetes. As an example, using the functional flux information derived from isotopomer analysis of plasma ketones we can determine hepatic ketogenesis during various stages of insulin resistance, a dominant route of fat oxidation in mice.
Update in the Treatment of T2DM
Dr. Cusi’s grants focus on cutting-edge research in adult endocrinology, diabetes and metabolism, both on clinical and basic research aspects related to the role of obesity and lipotoxicity in the development of Type 2 diabetes and its complications, in particular, the pathogenesis of NAFLD. He has published more than 90 original articles, invited reviews and book chapters in the main journals in the fields of obesity, diabetes and liver disease. Dr. Cusi is a nationally and internationally recognized investigator and speaker on the impact of NAFLD in humans, including a frequently cited paper in the New England Journal of Medicine on the first effective pharmacological agent for the treatment of NAFLD, a common and potentially serious complication of obesity and T2DM that may lead to severe liver damage. He is a reviewer in numerous scientific journals. Dr. Cusi is also vice-president and co-founder of Children in Need, Inc., an organization created to assist disadvantaged children and their families in third world countries, with emphasis on hospitals and schools in Southern Africa.
Dr. Bril’s current research interest focuses in understanding the metabolic impact that nonalcoholic fatty liver disease (NAFLD), and specifically its more severe form nonalcoholic steatohepatitis (NASH), may have in patients with obesity and/or type 2 diabetes. He is involved in several clinical research studies assessing the prevalence of NAFLD in specific ethnic groups using the gold-standard proton magnetic resonance spectroscopy (1H-MRS), and also in randomized clinical trials assessing different drugs that could potentially be used to treat this condition. Since joining Dr. Kenneth Cusi’s research group at UF, he has made some valuable contributions to the field, including two recent articles on the role of plasma vitamin D (http://www.ncbi.nlm.nih.gov/pubmed/25195551) and impaired insulin clearance (http://www.ncbi.nlm.nih.gov/pubmed/24777953) to the development of NAFLD and NASH.