Research Chemist, Medical Research Service, SFVAMC
Research Biochemist, Department of Molecular Biology, UCSF
Email: william.mcintire@ucsf.edu

Dr. McIntire works to develop treatments for cancer, heart disease, asthma, and other disorders that involve oxidative stress due to the aberrant production of reactive oxygen species (ROS). His research focuses on enzymes containing reduction-oxidation, or redox, cofactors, which are substances that certain enzymes need to carry out their reactions. Dr. McIntire is interested in the medical and pharmacological importance of human polyamine oxidase (PAO), a protein involved in cell metabolism. He was the first to clone and sequence the gene for PAO and to obtain pure enzyme for biochemical and pharmacological studies. His research group was the first to determine how PAO is inhibited by a well-known drug. These efforts will result in a better understanding of fundamental cellular processes such as cancer, cell death, oxidative stress, tissue damage, tissue differentiation and development, and wound healing. Dr. McIntire is also interested in the production of superoxide by Complex II (aka succinate dehydrogenase) of mitochondria, and is using the E. coli complex as a model to study in detail the mechanism of action and its involvement in ROS formation. More recently, he has become interested in the biochemistry, structure and function of human NADPH oxidase and its involvement in ROS generation, which contributes to numerous diseases.

Rajagukguk S, McIntire WS, Efimov I. 2008. Potential modulation of complex II activity through heme axial ligand substitutions. In Flavins and Flavoproteins 2008, 16th International Symposium (S. Frago, C. Gomez-Moreno & M. Medina, eds.). Prensas Universitarias de Zaragoza: 57-62.

Heuts DPHM, McIntire WS, Scrutton NS, Fraaije MW. 2009. Covalent cofactor binding in flavoproteins: On the role and mechanism of covalent flavinylation. FEBS J (In press).