Photo of Masao Kaneki,   M.D. Ph.D.

Masao Kaneki, M.D. Ph.D.

Massachusetts General Hospital

Massachusetts General Hospital


mkaneki@partners.org

Masao Kaneki, M.D. Ph.D.

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Anesthesia, Harvard Medical School
  • Associate Biochemist, Anesthesia & Critical Care, Massachusetts General Hospital
  • Director, Signal Transduction Laboratory, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

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.

Publications

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  • Sugita H, Kaneki M, Furuhashi S, Hirota M, Takamori H, Baba H. Nitric oxide inhibits the proliferation and invasion of pancreatic cancer cells through degradation of insulin receptor substrate-1 protein. Mol Cancer Res 2010; 8:1152-63. PubMed
  • Shinozaki S, Inoue Y, Yang W, Fukaya M, Carter EA, Ming-Yu Y, Fischman A, Tompkins R, Kaneki M. Farnesyltransferase inhibitor improved survival following endotoxin challenge in mice. Biochem Biophys Res Commun 2010; 391:1459-64. PubMed
  • Kaneki M, Shinozaki S, Chang K, Shimizu N. Could insulin sensitization be used as an alternative to intensive insulin therapy to improve the survival of intensive care unit patients with stress-induced hyperglycemia? Crit Care Med 2009; 37:2856-8. PubMed
  • Kaneki M. [Is ucOC a novel bone-derived anti-diabetogenic hormone in humans?] Clin Calcium 2009; 19:1304-10. PubMed
  • Sugita M, Sugita H, Kaneki M. Farnesyltransferase inhibitor, manumycin a, prevents atherosclerosis development and reduces oxidative stress in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2007; 27:1390-5. PubMed
  • 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 2005; 25:176-85. PubMed
  • Sugita H, Fujimoto M, Yasukawa T, Shimizu N, Sugita M, Yasuhara S, Martyn JA, Kaneki M. Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem 2005; 280:14203-11. PubMed
  • Yasukawa T, Tokunaga E, Ota H, Sugita H, Martyn JA, Kaneki M. S-nitrosylation-dependent inactivation of Akt/protein kinase B in insulin resistance. J Biol Chem 2005; 280:7511-8. PubMed