Neuroscience Center at Massachusetts General
Massachusetts General Hospital –
Charlestown, MA 02129
Dr. Kaneki received his M.D. and Ph.D. degrees from the University of Tokyo in Japan, and postdoctoral training in Signal Transduction at Dana-Farber Cancer Institute, Harvard Medical School before joining the Massachusetts General Hospital.
The research focus of my laboratory is on stress/inflammatory signaling pathways in human diseases, including diabetes, atherosclerosis and critical illness (e.g., sepsis, burn injury). 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, and sepsis, using genetically engineered mice, pharmacological inhibitors and cell culture. 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 diabetes and sepsis, to investigate the molecular pathogenesis based on the proteomic approach. The following is a list of ongoing projects in the group:
1. Inducible nitric oxide and insulin resistance
2. Nitric oxide and pancreatic beta-cell damage
3. Protein farneslation and sepsis
4. Stress-associated insulin resistance
5. S-nitrosylation-mediated cell apoptosis and cellular senescence.
Dr. Kaneki, Department of Anesthesia, Critical Care and Pain Medicine.
Boston Area Diabetes Endocrinology Research Center
Dana-Farber/ Harvard Cancer Center
here to access a full PubMed search on Dr. Kaneki
- Yasukawa,T., Tokunaga, E., Ota, H., Sugita, H., Martyn, J.A.J., Kaneki, M. S-nitrosylation-dependent inactivation of Akt/PKB in insulin resistance. J Biol Chem 2005; 280: 7511-7518.
- Sugita, H., Fujimito, M., Yasukawa, T., Shimizu, N., Sugita, M., Yasuhara, S., Martyn, J.A.J., Kaneki, M. iNOS and NO donor induce IRS-1 degradation in skeletal muscle cells. J. Biol Chem 2005; 280(14):14203-11.
- Fujimoto, M., Shimizu, N., Kunii, K., Martyn, J.A.J., Ueki, K., Kaneki, M. A role for iNOS in fasting hyperglycemia and impaired insulin signaling in the liver of obese, diabetic mice. Diabetes 2005; 54(5):1340-8.
- Ota, H., Tokunaga, E., Chang, K., Hikasa, M., Iijima. K., Eto, M., Kozaki, K., Akishita, M., Ouchi, Y., Kaneki, M. Sirt1 inhibitor, Sirtinol , induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene 2006; 25(2):176-85.
- Kaneki, M., Shimizu, N., Yamada D., Chang, K. Nitrosative stress and pathogenesis of insulin resistance. Antioxid Redox Signal, 2007, 9(3):319-29.
- Sugita, M., Sugita, H., Kaneki, M. Farnesyltransferase inhibitor, manumycin A, prevents atherosclerosis development and reduces oxidative stress in ApoE-deficient mice. Arterioscler Thromb Vasc Biol, 2007; 27(6): 1390-5.