The chemistry, biochemistry, physiology, and pharmacology of biogenic amines, their amino acid precursors and metabolic products, and various synthetic derivatives thereof have been investigated. The areas of specific interest are: 1) Determination of the primary sequence of catechol-O-methyltransferase (COMT) and construction of a COMT-specific cDNA probe; 2) The immunohistochemical localization of COMT in malignant, physiologically and hormonally modified, and normal tissues from rodent, and human at the light and electron microscopic level including: examination of the temporal and hormonal relationship between uterine epithelial COMT during the course of pregnancy in rat and hamster, study of the relationship between breast ductal epithelial-COMT and lactation in rat and mouse, study of COMT in both normal and malignant breast tissue in women with regard to the relationship between both type and extent of malignancy, the occurrence of increased COMT levels in gynomasty in man, and the distribution of COMT in endothelial and smooth muscle cells in the vascular system; 3) A study of the chemical and biological properties of various fluoro derivatives of biogenic amines, amino acids, and related compounds including studies of: the electrochemical, redox properties and electron densities of fluorocatechols, the interaction of fluorophenylephrines and fluoroepinephrines with both alpha and beta receptor systems, interaction at the active site of COMT and monoamine oxidase A and B, the uptake and metabolism of 6-fluorodopa and 6-fluorodihydroxyphenylserine in vitro and in vivo, the application of fluorine-18 analogs of dopa on dihydroxyphenylserine as PETT scanning agents for dopamine and norepinephrine neurons in the intact animal; the mechanism of toxicity of 2-fluorohistidine in leukemic mice, and the uptake and mechanism of toxicity of 6-fluorodopa in cultured pheochromocytoma and melanoma cell lines.
