Osamu Takeuchi，M.D., Ph.D.
Immune responses are elaborately regulated to achieve elimination of infected pathogens as well as prevention of development of immune diseases by excess activation of the immune system. Our laboratory aims to understand the mechanisms how the immune system balance is maintained by especially focusing on RNA regulatory systems in cells. With our results based on molecular biology and in vivo genetically modified mouse analysis, we also pursue developing novel technologies to manipulate immune responses.
Research and EducationViral and bacterial infection is initially recognized by the host innate immune system. Pattern recognition receptors such as Toll-like receptors (TLRs) initiate intracellular signaling pathways leading to the production of cytokines and immune responses. Inflammation evoked by immune reactions is related not only to infectious diseases, but also to various common diseases including autoimmune disease, cancer and metabolic disorders. We are studying molecular mechanisms of inflammation from innate immunity point of view. Particularly we are focusing on transcriptional and posttranscriptional regulation of genes relating to inflammation. We discovered an RNase, named Regnase-1, which is responsible for destabilizing cytokine mRNAs and prevention of inflammatory diseases. However, the system of immune regulation via RNAs is still mostly unknown. We will study the molecular mechanisms of RNA-mediated immune regulation and their roles in vivo by taking advantage of various techniques.
Graduate students in our lab will learn skills on molecular biology and immunology. We welcome young students who are interested in our research.
- Nakatsuka, Y., Vandenbon, A., Mino, T., Yoshinaga, M., Uehata, T., Cui, X., Sato, A., Tsujimura, T., Suzuki, Y., Sato, A., Handa, T., Chin, K., Sawa, T., Hirai, T., Takeuchi, O. (2018). Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia. Mucosal Immunology 11, 1203-1218. doi: 10.1038/s41385-018-0024-5.
- Yoshinaga, M., Nakatsuka, Y., Vandenbon, A., Ori, D., Uehata, T., Tsujimura, T., Suzuki, Y., Mino, T., Takeuchi, O. (2017). Regnase-1 maintains iron homeostasis via the degradation of transferrin receptor 1 and prolyl hydroxylase domain-containing protein 3 mRNAs. Cell Reports 19, 1614-1630.
- Mino, T., Murakawa, Y., Fukao, A., Vandenbon, A., Wessels, H.-H., Ori, D., Uehata, T., Tartey, S., Akira, S., Suzuki, Y., Vinuesa, C.G., Ohler, U., Standley,D.M., Landthaler, M., Fujiwara, T., Takeuchi, O. (2015). Regnase-1 and Roquin Regulate a Common Element in Inflammatory mRNAs by Spatiotemporally Distinct Mechanisms. Cell 161, 1058–1073.
- Tartey, S., Matsushita, K., Vandenbon, A., Ori, D., Imamura, T., Mino, T., Standley, D.M., Hoffmann, J.A., Reichhart, J.M., Akira, S., Takeuchi, O. (2014). Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex. EMBO J. 33, 2332-2348.
- Uehata, T., Iwasaki, H., Vandenbon, Matsushita, K., Cuellar, E.H., Kuniyoshi, K., Satoh, T., Mino, T., Suzuki, Y., Standley, D.M., Tsujimura, T., Rakugi, H., Isaka, Y., Takeuchi, O., Akira, S. (2013). Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation. Cell 153, 1036-1049.
LaboratoryProfessor: Osamu Takeuchi
Associate Professor: Takashi Mino
Associate Professor: Takuya Uehata