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Ken Inoki, M.D., Ph.D.

Research Summary:

Ken Inoki is investigating the function and regulation of the mTOR signaling pathway. Disregulation of this pathway is involved in development of human disease including cancer and diabetes. By using biochemical and genetic approaches, Dr. Inoki is investigating the function and regulation of MTOR in hopes to elucidate its role in the development and progression of human diseases.

Link to PubMed Citations

Selected Publications:

Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH, Inoki K, Guan KL, Shen J, Person MD, Kusewitt D, Mills GB, Kastan MB, Walker CL. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4153-8. Epub 2010 Feb 16.

Izumi K, Inoki K, Fujimori Y, Marcelo CL, Feinberg SE. Pharmacological retention of oral mucosa progenitor/stem cells. J Dent Res. 2009 Dec;88(12):1113-8. Epub 2009 Nov 5.

Diallo-Krou E, Yu J, Colby LA, Inoki K, Wilkinson JE, Thomas DG, Giordano TJ, Koenig RJ. Paired box gene 8-peroxisome proliferator-activated receptor-gamma fusion protein and loss of phosphatase and tensin homolog synergistically cause thyroid hyperplasia in transgenic mice. Endocrinology. 2009 Nov;150(11):5181-90. Epub 2009 Sep 24.

Mori H, Inoki K, Opland D, Muenzberg H, Villanueva EC, Faouzi M, Ikenoue T, Kwiatkowski D, Macdougald OA, Myers Jr MG, Guan KL. Critical roles for the TSC-mTOR pathway in {beta}-cell function. Am J Physiol Endocrinol Metab. 2009 Aug 18. [Epub ahead of print]

Mori H, Inoki K, Masutani K, Wakabayashi Y, Komai K, Nakagawa R, Guan KL, Yoshimura A. The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential. Biochem Biophys Res Commun. 2009 Jul 10;384(4):471-5. Epub 2009 May 5.

Zhou X, Ikenoue T, Chen X, Li L, Inoki K, Guan KL. Rheb controls misfolded protein metabolism by inhibiting aggresome formation and autophagy. Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):8923-8. Epub 2009 May 20.

Inoki K, Guan KL. Tuberous sclerosis complex, implication from a rare genetic disease to common cancer treatment. Hum Mol Genet. 2009 Apr 15;18(R1):R94-100. Review.

Mori H, Inoki K, Münzberg H, Opland D, Faouzi M, Villanueva EC, Ikenoue T, Kwiatkowski D, MacDougald OA, Myers MG Jr, Guan KL. Critical role for hypothalamic mTOR activity in energy balance. Cell Metab. 2009 Apr;9(4):362-74.

Ikenoue T, Hong S, Inoki K. Monitoring mammalian target of rapamycin (mTOR) activity. Methods Enzymol. 2009;452:165-80.

Inoki K. Role of TSC-mTOR pathway in diabetic nephropathy. Diabetes Res Clin Pract. 2008 Nov 13;82 Suppl 1:S59-62. Epub 2008 Oct 15. Review.

Buller CL, Loberg RD, Fan MH, Zhu Q, Park JL, Vesely E, Inoki K, Guan KL, Brosius FC 3rd. A GSK-3/ TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression. Am J Physiol Cell Physiol. 2008 Sep;295(3):C836-43. Epub 2008 Jul 23.

Ikenoue T, Inoki K, Zhao B, Guan KL. PTEN acetylation modulates its interaction with PDZ domain. Cancer Res. 2008 Sep 1;68(17):6908-12.

Ikenoue T, Inoki K, Yang Q, Zhou X, Guan KL. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J. 2008 Jul 23;27(14):1919-31. Epub 2008 Jun 19. Erratum in: EMBO J. 2008 Aug 20;27(16):2270.

Lee CH, Inoki K, Karbowniczek M, Petroulakis E, Sonenberg N, Henske EP, Guan KL. Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53. EMBO J. 2007 Nov 28;26(23):4812-23. Epub 2007 Oct 25.

Lee CH, Inoki K, Guan KL. mTOR pathway as a target in tissue hypertrophy. Annu Rev Pharmacol Toxicol. 2007;47:443-67. Review.

Yang Q, Inoki K, Ikenoue T, Guan KL. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev. 2006 Oct 15;20(20):2820-32.

Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO, Guan KL. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 2006 Sep 8;126(5):955-68.

Yang Q, Inoki K, Kim E, Guan KL. TSC1/ TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Proc Natl Acad Sci U S A. 2006 May 2;103(18):6811-6. Epub 2006 Apr 20.

Inoki K, Guan KL. Complexity of the TOR signaling network. Trends Cell Biol. 2006 Apr;16(4):206-12. Epub 2006 Mar 3.

Chong-Kopera H, Inoki K, Li Y, Zhu T, Garcia-Gonzalo FR, Rosa JL, Guan KL. TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. J Biol Chem. 2006 Mar 31;281(13):8313-6. Epub 2006 Feb 7.

Li Y, Inoki K, Vikis H, Guan KL. Measurements of TSC2 GAP activity toward Rheb. Methods Enzymol. 2006;407:46-54.

Guo B, Inoki K, Isono M, Mori H, Kanasaki K, Sugimoto T, Akiba S, Sato T, Yang B, Kikkawa R, Kashiwagi A, Haneda M, Koya D. MAPK/AP-1-dependent regulation of PAI-1 gene expression by TGF-beta in rat mesangial cells. Kidney Int. 2005 Sep;68(3):972-84.

Corradetti MN, Inoki K, Guan KL. The stress-inducted proteins RTP801 and RTP801L are negative regulators of the mammalian target of rapamycin pathway. J Biol Chem. 2005 Mar 18;280(11):9769-72. Epub 2005 Jan 4.

Inoki K, Ouyang H, Li Y, Guan KL. Signaling by target of rapamycin proteins in cell growth control. Microbiol Mol Biol Rev. 2005 Mar;69(1):79-100. Review.

Inoki K, Corradetti MN, Guan KL. Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet. 2005 Jan;37(1):19-24. Review.

Li Y, Inoki K, Guan KL. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol. 2004 Sep;24(18):7965-75.

Corradetti MN, Inoki K, Bardeesy N, DePinho RA, Guan KL. Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev. 2004 Jul 1;18(13):1533-8.

Li Y, Corradetti MN, Inoki K, Guan KL. TSC2: filling the GAP in the mTOR signaling pathway. Trends Biochem Sci. 2004 Jan;29(1):32-8. Review.

 
     
   

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