a. Molecular basis of cerebral energy utilization and failure
The Colleen Giblin Laboratories, in the context of the Division of Pediatric Neurology at the Columbia University Irving 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, pyruvate dehydrogenase deficiency and pyruvate carboxylase deficiency, among other mitochondrial disorders, were first identified/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.
- 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.
- 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.
- The molecular genetics, pathogenesis and clinical forms of Pyruvate carboxylase deficiency.
- The natural history and therapy of the syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS), a prototype mitochondrial disease.
Patients participating in these NIH-sponsored research projects travel to the site of our laboratories and take part in functional brain imaging and neuropsychological assessment techniques, as well as other research related study procedures being developed in conjunction with the Laboratories.
b. Molecular excitability disorders
This research program was developed in response to the great expansion and renewed attention these disorders have experienced since the advent of molecular genetics and the patch clamp, two major tools used in combination at the Laboratories. Diseases of interest include epilepsy, arrhythmia, genetic myopathies and neurotoxicity.
The Giblin Laboratories add the expertise of scientists interested in ion channel structure, function and pharmacological modification to the well-established tradition of clinical study and discovery of excitability disorders of muscle, nerve, and brain at the Neurological Institute.
The clinical aspect of this research program benefits from the availability of the Irving Institute for Clinical and Translational Research, an NIH-funded investigational resource where patients and their families are studied and followed. Patients are also seen at our affiliated space in the Spinal Muscular Atrophy Clinical Research Center. Involvement of basic and clinical researchers in group discussions of patient assessment and management is strongly encouraged, in order to cross-fertilize participating scientists and clinicians and to nurture the exchange of ideas from all traditional disciplines. Opportunities for interaction with other groups interested in excitability from molecular, cellular, systems or cognitive perspectives are emphasized.