Neuroscience Center at MGH

Masao Kaneki MD, Ph.D.
Neuroscience Center at Massachusetts General Hospital

Massachusetts General Hospital – East
Building 149
13th Street
Charlestown, MA 02129

Telephone: 617-726-8122
E-mail: MKANEKI@HELIX.MGH.HARVARD.EDU

Biography
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.

Research Program
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.

Boston Area Diabetes Endocrinology Research Center

Dana-Farber/ Harvard Cancer Center

Publications
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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.