Uniformed Services University of the Health Sciences
4301 Jones Bridge Road
Bethesda, Maryland 20814
Pathogenesis of Canavan disease and its treatment. Canavan disease is a neurodegenerative disorder caused by mutations in the enzyme aspartoacylase that degrade N-acetylaspartate into acetate and aspartate. Currently, no treatment is available for Canavan disease. Efforts are focused on a) developing an animal model for Canavan disease by knocking out aspartoacylase gene in the mouse and b) testing acetate supplementation as a therapy.
Functional roles of N-acetylaspartate and N-acetylaspartylglutamate in the nervous system. Current efforts involve cloning of the gene for aspartate N-acetyltransferase, a nervous system specific enzyme involved in the biosynthesis of N-acetylaspartate and N-acetylaspartylglutamate. Subsequent efforts would involve making a gene knockout system to study the functional roles.
Melatonin and circadian rhythms. Current efforts are focussed on structural studies of serotonin N-acetyltransferase, the enzyme responsible for the circadian regulation of melatonin production. Long term goals include development of inhibitors of the enzyme for use as drugs to control serotonin and melatonin levels in human.
Physiological and pathological roles of kynurenine pathway activation in the neuroimmune system. Earlier studies from this laboratory have shown that macrophages and dendritic cells are the primary sites of kynurenine pathway activation that occurs in response immune stimulations. Recent studies have shown that this is an important mechanism by which macrophages and dendritic cells regulate T-cell functions. Current efforts are focussed on identifying the genes that are regulated in response to kynurenine pathway activation in mixed cell cultures of T cells and macrophages using DNA microarray techniques.