Dr. Halsted's research activities focus on the regulation of folate absorption and metabolism in health and various diseases. His group characterized the properties of folate hydrolase, an intestinal enzyme that regulates folate absorption. These studies included the molecular sequence of its gene glutamate carboxypeptidase (GCPII) and identification of a unique polymorphism in GCPII associated with decreased enzyme activity. Ongoing work focuses on GCPII genotype screening of human populations who are at risk for folate deficiency with attendant hyperhomocysteinemia and its associated clinical conditions that include increased risks for cardiovascular diseases, neural tube defects, and decreased cognition in aging. A second active research program evaluates the roles of folate deficiency and hyperhomocysteinemia in the pathogenesis of alcoholic liver disease. Using a micropig model, his group demonstrated that the development of alcoholic liver disease was promoted by the combination of folate deficiency with hyperhomocysteinemia and alcohol feeding. Ongoing studies focus on disease mechanisms including effects of alcohol exposure on enzymes that regulate homocysteine metabolism and the potential effects of increased homocysteine and its related metabolites on signal pathways for liver injury.