現在の研究プロジェクト

スタッフを中心に大きく2つの研究グループに分かれて研究を行っています。それぞれのグループ間に垣根はなく、互いに協力しながら研究を進めています。


蛋白質分解機構による感染防御応答の制御(齊藤准教授グループ)  
蛋白質は、おもにユビキチン・プロテアソーム系とライソゾーム系の働きにより分解・代謝されます。本グループでは、感染防御関連因子の制御において蛋白質分解機構が担っている役割の解明を目指して、解析を行っています。  

Saitoh T*, Fujita N*, Hayashi T, Takahara K, Satoh T, Lee H, Matsunaga K, Kageyama S, Omori H, Noda T, Yamamoto N, Kawai T, Ishii K, Takeuchi O, Yoshimori T, Akira S.
Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response.
 (*These authors equally contributed to this work)
Proc Natl Acad Sci U S A. 2009 106:20842-6.
 
Fujita N, Saitoh T, Kageyama S, Akira S, Noda T, Yoshimori T.
Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: analysis of the organization of the Atg16L1 complex in fibroblasts.
J Biol Chem. 2009 Nov 20;284(47):32602-9.
 
Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T.
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages.
Nat Cell Biol. 2009 Apr;11(4):385-96.
 
Saitoh T*, Fujita N*, Jang MH, Uematsu S, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M, Tanaka K, Kawai T, Tsujimura T, Takeuchi O, Yoshimori T, Akira S.
Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production.
 (*These authors equally contributed to this work)
Nature. 2008 Nov 13;456(7219):264-8.
 
Yamamoto M, Sato S, Saitoh T, Sakurai H, Uematsu S, Kawai T, Ishii KJ, Takeuchi O, Akira S.
Cutting Edge: Pivotal function of Ubc13 in thymocyte TCR signaling.
J Immunol. 2006 Dec 1;177(11):7520-4.
 
Yamamoto M, Okamoto T, Takeda K, Sato S, Sanjo H, Uematsu S, Saitoh T, Yamamoto N, Sakurai H, Ishii KJ, Yamaoka S, Kawai T, Matsuura Y, Takeuchi O, Akira S.
Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling.
Nat Immunol. 2006 Sep;7(9):962-70.
 
Saitoh T, Tun-Kyi A, Ryo A, Yamamoto M, Finn G, Fujita T, Akira S, Yamamoto N, Lu KP, Yamaoka S.
Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1.
Nat Immunol. 2006 Jun;7(6):598-605.
 
Saitoh T, Yamamoto M, Miyagishi M, Taira K, Nakanishi M, Fujita T, Akira S, Yamamoto N, Yamaoka S.
A20 is a negative regulator of IFN regulatory factor 3 signaling.
J Immunol. 2005 Feb 1;174(3):1507-12.
 
Yamamoto M, Yamazaki S, Uematsu S, Sato S, Hemmi H, Hoshino K, Kaisho T, Kuwata H, Takeuchi O, Takeshige K, Saitoh T, Yamaoka S, Yamamoto N, Yamamoto S, Muta T, Takeda K, Akira S.
Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta.
Nature. 2004 Jul 8;430(6996):218-22.
 
Saitoh T, Nakayama M, Nakano H, Yagita H, Yamamoto N, Yamaoka S.
TWEAK induces NF-kappaB2 p100 processing and long lasting NF-kappaB activation.
J Biol Chem. 2003 Sep 19;278(38):36005-12.
 
Saitoh T, Nakano H, Yamamoto N, Yamaoka S.
Lymphotoxin-beta receptor mediates NEMO-independent NF-kappaB activation.
FEBS Lett. 2002 Dec 4;532(1-2):45-51.

 

 

 

ノックアウトマウスを用いた自然免疫の包括的理解(佐藤助教グループ)
自然免疫への関与が考えられる分子を欠損した遺伝子改変マウスを作製し、そのフェノタイプから、免疫系への役割を明らかにしようとしています。また、ノックアウトマウス間で遺伝子発現の比較検討を行い、遺伝子発現ネットワークの包括的理解を目指しています。

 

Uehata T, Iwasaki H, Vandenbon A, Matsushita K, Hernandez-Cuellar E, Kuniyoshi K, Satoh T, Mino T, Suzuki Y, Standley DM, Tsujimura T, Rakugi H, Isaka Y, Takeuchi O, Akira S

Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation.

Cell. 2013 153:1036-49.

 

Satoh T, Kidoya H, Naito H, Yamamoto M, Takemura N, Nakagawa K, Yoshioka Y, Takakura N, Takeuchi O, Akira S

Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages.

Nature. 2013 495:524-28.

 

Iwasaki H, Takeuchi O, Teraguchi S, Matsushita K, Uehata T, Kuniyoshi K, Satoh T, Saotoh T, Matsushita M, Standley DM, Akira S

The IkB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1.

Nat Immunol. 2011 12:1167-75.

 

Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui k, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S 

The Jmjd3-Irf4 axis regulates M2 mactophage polarization and host responses against helminth infection.

Nat Immunol. 2010 11:936-44.

 
Matsushita K*, Takeuchi O*, Standley DM, Kumagai Y, Kawagoe T, Miyake T, Satoh T, Kato H, Tsujimura T, Nakamura H, Akira S (*equal contribution)
Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay.
Nature 2009 458: 1185-90.
 





 

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