Molecular basis of cerebral energy utilization and failure

The Colleen Giblin Laboratories, in the context of the Division of Pediatric Neurology at the Columbia Presbyterian Medical Center, enjoy a distinguished tradition of metabolic disease research and discovery.  The Laboratories and the Division also remain at the forefront of investigative and clinical excellence in other areas such as sickle cell encephalopathy, pediatric brain tumors, pediatric epilepsy, storage diseases, fetal neurotoxicity and functional neuroimaging.  Diseases like Reye syndrome, glucose transporter deficiency (Glut-1 DS), carnitine deficiency, and pyruvate dehydrogenase and carboxylase deficiencies, among other mitochondrial disorders, were first identified and/or successfully treated by members of the Division.  An unusually large patient base comprising referrals from every part of the world is available for metabolic research.  A tissue culture bank containing some 1,000 samples with accompanying clinical descriptions has been established by Dr. De Vivo and constitutes a unique investigational resource. 

Our efforts are currently devoted to the central steps of energy metabolism and integrate molecular and clinical aspects, a research paradigm that will be adopted by most institutions in the future.  Projects include: 1) The molecular genetics, pathogenesis, diagnosis and therapy of Glut-1 DS.  The Laboratories serve as the major referral center for diagnosis and mutation identification in the world and carry out natural history studies and therapeutic trials.   2) Pyruvate dehydrogenase function, regulation, and deficiency.  The identification of modulatory genes involved in the function of this crucial metabolic process, aided by the molecular study of patients and families with uncommon forms of pyruvate dehydrogenase deficiency, is under way.  3) Pyruvate carboxylase gene structure and clinical forms of deficiency.  4) The natural history and therapy of the syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS), a prototype mitochondrial disease. 

Patients collaborating in these NIH-sponsored research projects are studied at the Irving Clinical Research Center and are also subject to investigative functional brain imaging and neuropsychological assessment techniques being developed in conjunction with the Laboratories.