Kazuhiro Iwai, M.D., Ph.D. Professor
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 signaling regulating NF-kB activation and cell death mediated by novel ubiquitin modification called linear ubiquitination, and iron metabolism in order to develop a new clinical therapy against chronic inflammatory disease and cancer.
Research and EducationWe are conducting two research projects.
!) Functional analysis of the novel ubiquitin modification called linear ubiquitination, which is specifically generated by the LUBAC ubiquitin ligase. We found that the linear ubiquitin chain plays an important role in controlling inflammation, carcinogenesis, and immune response through activation of the transcription factor NF-kB and suppression of programmed cell death. It also shows that increased production or suppression of linear ubiquitin chains causes the development of lymphoma and autoinflammatory diseases.
2) Cellular iron metabolism.
Iron is an essential trace metal that binds to proteins as iron ions or in the form of iron prosthetic groups called heme and iron-sulfur clusters, and functions for oxygen transport and ATP production. Recently, iron-induced cell death, ferroptosis, is gaining attention due to its association with cancer and ischemic diseases. In addition to ferroptosis, we are focusing on iron-induced liquid-liquid phase separation of proteins and autophagy.
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
- Fuseya, Y., Fujita, H., Kim, M., Ohtake, F., Nishide, A., Sasaki, K., Saeki, Y., Tanaka, K., Takahashi, R. and Iwai, K. The HOIL-1L ligase modulates immune signaling and cell death via mono-ubiquitination of LUBAC. Nature Cell Biology. 22(6):663-673, 2020.
- S Sasaki, K., Himeno, A., Nakagawa, T., Sasaki, Y., Kiyonari, H. and Iwai, K. Modulation of autoimmune pathogenesis by T cell-triggered inflammatory cell death. Nature Commun. 10(1):3878. doi:10.1038/s41467-019-11858-7.
- Fujita,, Tokunaga, A., Shimizu, S., Whiting, A. L., Aguilar-Alonso, F., Takagi, K., Walinda, E., Sasaki, Y., Shimokawa, T., Mizushima, T., Ohki, I., Ariyoshi, M., Tochio, H., Bernal, F., Shirakawa, M., and Iwai, K. Cooperative domain formation by homologous motifs in HOIL-1L and SHARPIN plays crucial roles in LUBAC stabilization. Cell Reports 23(4):1192-1204, 2018.
- Asano, T., Koike, M., Sakata, S.-I., Takeda, Y., Nakagawa, T., Hatano, T., Ohashi, S., Funayama, M., Yoshimi, K., Asanuma, M., Toyokuni, S., Mochizuki, H., Uchiyama, Y., Hattori, N., and Iwai, K. Possible involvement of iron-induced oxidative insults in neurodegeneration. Lett. 588:29-35, 2015.
- 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.
Molecular and Cellular PhysiologyProfessor：Kazuhiro Iwai
Senior Lecturers：Katsuhiro Sasaki
Assistant Professor：Hiroaki Fujita
Assistant Professor：Yasuhiro Fuseya
Assistant Professor：Tomoyasu Jo