Oxidoreductases in Cellular Defense and Signaling. Search of inhibitors for therapeutic purposes

Our current research is focused on the enzymology and molecular biology of oxidoreductases involved in mechanisms of cellular defense and signaling. We are investigating members of three oxidoreductase superfamilies participating in the metabolism of carbonyl compounds, along with other biological functions: aldo-keto reductases (AKR), medium-chain dehydrogenases/reductases (MDR) and aldehyde dehydrogenases (ALDH). We are especially interested in enzymes acting on the metabolism of signaling molecules (retinoids and prostaglandins) and associated with different human disease states, such as cancer and diabetes. Some of these enzymes are also phase I-drug metabolizing enzymes and are induced under oxidative stress, being responsible for developing tumor resistance to chemotherapy. Thus, they are relevant drug targets and are well suited for the design of selective enzyme inhibitors with potential use as pharmacological agents. Some illustrative examples of the enzymes being studied are zeta-crystallin, an RNA-binding protein involved in the cellular stress response; pro-apoptotic p53-induced gene protein 3 (PIG3); and aldo-keto reductase 1B10 (AKR1B10), a highly efficient retinaldehyde dehydrogenase which is induced in several types of cancer.