Contact Us

Mailing address:
Department of Environmental and Molecular Toxicology
Box 7633, NC State University
Raleigh, NC 27695-7633

Shipping address:
Suite 1104, 850 Main Campus Dr.
Raleigh, NC 27606

Phone 919.515.2274
Fax 919.515.7169

 

 

 

 

 

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Jun Ninomiya-Tsuji, Ph.D.
Associate Professor
Department of Environmental and Molecular Toxicology

E-mail: Jun_Tsuji@ncsu.edu





   
Lab Members  
Rie Kajino-Sakamoto Postdoctoral Research Associate
Emily Omori Postdoctoral Research Associate
Peter Broglie Graduate Student
Sho Morioka Graduate Student


Former Lab Members  
Satoshi Kishida Assistant Professor at Nagoya University, JAPAN
Taisuke Kajino Postdoctoral Fellow at Duke University, NC
Wei-Chun Huang-Fu Postdoctoral Fellow at University of Pennsylvania, PA
Noriyuki Uemura Postdoctoral Fellow at Chubu University, JAPAN
Maiko Inagaki Assistant Professor at Hiroshima University, JAPAN
Jae-Young Kim Postdoctoral Fellow at The Burnham Institute, CA

 

 

Research Interests

Signaling networks activated by stress and cytokines in mammalian cells; the role of TAK 1 kinase cascades

Stress and cytokines initiate intracellular signaling pathways including various kinase cascades to protect cells from damages and infection. Recent research is revealing that these signal transduction pathways intersect and influence one another. Specificity and crosstalk of signaling pathways appear to be important for cellular responses.

We have been studying MAP kinase cascades. TAK1 is a member of MAP kinase kinase kinase (MAPKKK), which is activated by various stressors and cytokines including transforming growth factor beta (TGF-beta), tumor necrosis factor (TNF) and interleukin-1 (IL-1). We have demonstrated that TAK1 participates in TGF-beta, TNF and IL-1 signaling, and Wnt signaling. Our current research is aimed at elucidation of mechanisms of how TAK1 is activated by various stimuli, and identification of the targets of TAK1 in the signaling pathways in culture cells and in an in vivo setting. We are also focusing on identification of mechanisms that regulate specificity of each TAK1 signaling pathway and crosstalk between the signaling pathways.

 

 

Rie Kajino-Sakamoto, Postdoctoral Research Associate

Role of TAK1 in intestinal homeostasis

 

 

 

 

 

 

 

 

 

Emily Omori, Postdoctoral Research Associate

Roles of TAK1 in skin inflammation and keratinocyte survival

 

 

 

 

 

 

 

 

 

Peter Broglie, Graduate Student

Role of TAB2 in cytokine signaling

Downregulation of TAK1 is important for preventing excessive inflammation

 

 

 

 

Sho Morioka, Graduate Student

TAK1 regulation of tissue homeostasis

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Ninomiya-Tsuji's publications

Selected Publications

  • Morioka, S., Omori, E., Kajino, T., Kajino-Sakamoto, R., Matsumoto, K., and Ni-nomiya-Tsuji, J. (2009). TAK1 kinase determines TRAIL sensitivity by modulating reactive oxygen species and cIAP. Oncogene 2009/05/08 [aheadofprint].

  • Kim, J.-Y., Kajino-Sakamoto, R., Omori, E., Jobin, C., and Ninomiya-Tsuji, J. (2009). Intestinal epithelial-derived TAK1 signaling is essential for cytoprotection against chemical-induced colitis. PLoSONE, 4, e4561
  • Inagaki, M., Omori, E., Kim, J.Y., Komatsu, Y., Scott, G., Ray, M.K., Yamada, G., Matsumoto, K., Mishina, Y., and Ninomiya-Tsuji, J. (2008). TAK1-binding Protein 1, TAB1, Mediates Osmotic Stress-induced TAK1 Activation but Is Dispensable for TAK1-mediated Cytokine Signaling. J. Biol. Chem. 283, 33080-33086
  • Omori, E., Morioka, S., Matsumoto, K., and Ninomiya-Tsuji, J. (2008). TAK1 regulates reactive oxygen species and cell death in keratinocytes, which Is essential for skin integrity. J. Biol. Chem. 283, 26161-26168
  • Kajino-Sakamoto, R., Inagaki, M., Lippert, E., Akira, S., Robine, S., Matsumoto, K., Jobin, C., and Ninomiya-Tsuji, J. (2008). Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis. J. Immunol. 180, 1143-1152
  • Prickett, T.D., Ninomiya-Tsuji, J., Broglie, P., Muratore, T.L., Shabanowitz, J., Hunt, D.F., and Brautigan, D.L. (2008). TAB4 stimulates TAK1-TAB1 phosphorylation and binds polyubiquitin to direct signaling to NF-kappaB. J. Biol. Chem.,19245-19254
  • Kim, J.-Y., Omori, E., Matsumoto, K., Nunez, G., and Ninomiya-Tsuji, J. (2008). TAK1 is a central mediator of NOD2 signaling in epidermal cells. J. Biol. Chem. 283, 137-144

  • HuangFu, W.-C., Matsumoto, K., and Ninomiya-Tsuji, J. (2007). Osmotic stress blocks NF-kappaB-dependent inflammatory responses by inhibiting ubiquitination of IkappaB. FEBS Lett. 581, 5549-5554

  • Kajino, T ., Omori, E ., Ishii, S., Matsumoto, K., and Ninomiya-Tsuji, J. (2007). TAK1 MAPK kinase kinase mediates transforming growth factor-beta signaling by targeting SnoN oncoprotein for degradation. J. Biol. Chem. 282, 9475-9481.

  • Kajino, T. , Ren, H., Iemura, S., Natsume, T., Stefansson, B., Brautigan, D. L., Matsumoto, K., and Ninomiya-Tsuji, J. (2006). Protein Phosphatase 6 Down-regulates TAK1 Kinase Activation in the IL-1 Signaling Pathway. J. Biol. Chem. 281, 39891-39896.

  • HuangFu, W.-C. , Omori, E. , Akira, S., Matsumoto, K., and Ninomiya-Tsuji, J. (2006). Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF-kappaB activation: TAO2 regulates TAK1 pathways. J. Biol. Chem. 281, 28802-28810.

  • Omori, E. , Matsumoto, K., Sanjo, H., Sato, S., Akira, S., Smart, R. C., and Ninomiya-Tsuji, J. (2006). TAK1 is a master regulator of epidermal homeostasis involving skin inflammation and apoptosis. J. Biol. Chem. 281, 19610-19617.

  • Uemura, N. , Kajino, T. , Sanjo, H., Sato, S., Akira, S., Matsumoto, K., and Ninomiya-Tsuji, J. (2006). TAK1 is a component of the Epstein-Barr virus LMP1 complex and is essential for activation of JNK but not of NF-kappaB. J. Biol. Chem. 281 , 7863-7872.

  • Kishida, S ., Sanjo, H., Akira, S., Matsumoto, K., and Ninomiya-Tsuji, J. (2005). TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway. Genes Cells 10 , 447-454.