Dr. Caro's work is directed primarily to the understanding of the physiologic and molecular mechanisms that regulate the expression of genes in response to hypoxia. Hypoxia activates the protein expression and transcriptional activity of the hypoxia-inducible complex HIF-1. This complex, in turn, binds to specific hypoxia-responsive elements in the promoter region of hypoxia-inducible genes. The molecular activation of HIF proteins involves hydroxylase enzymes that control the survival and activity of HIF proteins in an oxygen- and iron-dependent way. Dr. Caro's laboratory is currently investigating the mechanisms by which these hydroxylases act as oxygen sensors and regulate gene expression. Within the genes regulated by HIF proteins are those involved in glucose metabolism, oxygen transport and angiogenesis. Thus, the understanding of the mechanisms that control the activity of HIF proteins may have an important role in new therapeutic approaches to ischemic diseases and tumor treatment.