Research Abstract

My research group has been working on three major projects: (1) inducible nitric oxide synthase (iNOS) and protein S-nitrosylation (a covalent attachment of NO to cysteine thiols) in stress signaling; (2) Sirt1 NAD+-dependent deacetylase and stress resistance; and (3) protein isoprenylation, namely farnesylation and geranylgeranylation, in atherosclerosis, sepsis and cancer. We have shown that Sirt1 inhibition by itself is sufficient to induce senescence-like sustained growth arrest in a p53-independent manner in human cancer cells. We have been also investigating the roles of Sirt family proteins in DNA damage-induced stress signaling. Our research has identified iNOS and protein S-nitrosylation as the major mediator of obesity- and stress-induced insulin resistance, and type 2 diabetes. Moreover, my research team is currently identifying farnesylated or S-nitrosylated proteins in tissue samples in rodent models of human diseases, including cancer and diabetes, to investigate the molecular pathogenesis from the proteomic approach.