- D.Sc., 1992, Unit of Biochemistry, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Postdoctoral Training - Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey; Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
Oxidative damage to proteins is considered to be one of the major causes of aging and age-related diseases, and thus mechanisms have evolved to prevent or reverse these modifications. Methionine is one of the major targets of reactive oxygen species (ROS), where it is oxidized to methionine sulfoxide (MetO). Recently evidence has accumulated suggesting that methionine oxidation may play an important role in the progression of neurodegenerative diseases like Alzheimer's and Parkinson's disease. Oxidative alteration of Met to Met(O) is reversed by the methionine sulfoxide reductases (MsrA which reduces S-MetO and MsrB which reduces R-MetO). This may prevent irreversible protein damage and as a consequence extend the organism's life span. A major biological role of Msrs is suggested by the fact that the MsrA null mouse (MT) exhibits a neurological disorder in the form of ataxia ("tip toe walking"), is more sensitive to oxidative stress, and has a shorter life span (by~40%) than wild-type (WT) mice. However, a major open question is how these important antioxidants function, and is the methionine oxidation/reduction cycle analogous to the cysteine oxidation/reduction or protein-phosphorylation / dephosphorylation mechanisms involved in cell signaling. The specific aims of my research are designed to determine how the Msr system affects the function and expression of other proteins as well as to evaluate the role of methionine oxidation in the progression of oxidative stress and age related diseases.