Cells consisting of our body is must be maintained to be healthy. Deregulation of cellular function results in life-threating disorders, including cancer and neurodegenerative diseases. The aim of our research is to find out novel regulatory mechanisms of biological reactions and diseases. We are currently investigating the molecular basis of ubiquitination, diverse ubiquitin signaling regulating NF-kB activation and iron metabolism in order to develop a new clinical therapy against chronic inflammatory disease and cancer.
Research and Education
We are conducting two research projects.
1) Functional analysis of a novel ubiquitin ligase complex, LUBAC.
We identified LUBAC that specifically assembles a linear polyubiquitin chain and that LUBAC is involved in the activation of NF-kB, which plays pivotal roles in immune response, inflammation and tumorgenesis mediated by various stimuli. It is known that null mutation of a subunit of LUBAC has shown to causative to hereditary disorders showing autoinflammation and immunodeficiency.
2) Iron metabolism in cells.
Iron is an essential nutrient to exert numerous biological functions including oxygen transport and energy metabolism by binding to proteins as an iron ion, heme or iron-sulfur cluster. Mitochondria play central roles in iron metabolism by generating heme or iron-sulfur cluster. We are analyzing roles of mitochondria play in cellular iron sensing and iron-induced damage of mitochondria in diseases.
This laboratory is responsible for the education of physiology in Medical School. Many graduate students with various backgrounds conduct an individual research project under the supervision of faculty staffs.
Chronic dermatitis observed in SHARPIN lacking cpdm mice
- Sasaki, Y., Sano, S., Nakahara, M., Murata, S., Kometani, K., Aiba, Y., Sakamoto, S., Watanabe, Y., Tanaka, K., Kurosaki, K. and Iwai, K. Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells. EMBO J. 32: 2463- 2476, 2013.
- Ueta, R., Fujiwara, N., Iwai, K., and Yamaguchi-Iwai, Y. Iron-induced dissociation of the Aft1p transcriptional regulator from target gene promoters is an initial event in iron-dependent gene suppression. Mol. Cell. Biol. 32:4998-5008, 2012.
- Tokunaga F., Nakagawa T., Nakahara M., Saeki Y., Taniguchi M., Sataka S.-I., Tanaka K., Nakano H., Iwai K. Sharpin is a component of the NF-kB activating linear ubiquitin chain assembly complex. Nature. 471: 633-636, 2011.
- Tokunaga F., Sakata S., Saeki Y., Satomi Y., Kirisako T., Kamei K., Nakagawa T., Kato M., Murata S., Yamaoka S., Yamamoto M., Akira S., Takao T., Tanaka K., Iwai K. Involvement of linear polyubiquitylation of NEMO in NF-kB activation. Nat Cell Biol. 11: 123-132, 2009.
- Kirisako T., Kamei K., Murata S., Kato M., Fukumoto H., Kanie K., Sano S. Tokunaga F., Tanaka K., Iwai K. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 25: 4877-4887, 2006.
Molecular and Cellular Physiology
Associate Professor：Yoshiteru Sasaki
Assistant Professor：Yukiko Takeda
Assistant Professor：Hiroaki Fujita