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Toxicology and Safety Science(Medical and Health Sciences)

Tsutsumi YasuoProfessor

Mar. 1991: Bachelor of Pharmaceutical Science (Osaka Univ.), Oct. 1991: License to practice pharmacy, Aug. 1997: Ph.D. (Osaka Univ.). Aug. 1994:
Assistant Professor (Grad. Sch. Pharm. Sci., Osaka Univ.), Apr. 1999 – Jan 2001: Visiting fellow (NIH), Apr. 2004: Project Head (NIHS), Apr. 2005: Project leader (NIBIO), Apr. 2008 – present: Professor (Grad. Sch. Pharm. Sci., Osaka Univ.), Apr. 2012 – Mar. 2018: Dean (Grad. Sch. Pharm. Sci., Osaka Univ.), Apr. 2017 – present: Distinguished Professor (Osaka Univ.).

Research theme

Nano-Safety Science research of nanomaterial

We are working to collect safety information of nanomaterial with the aim of contributing to risk analysis by analyzing the relationship among physicochemical properties (particle size or surface charge), toxicokinetic [ADME] (absorption, distribution, metabolism, accumulation / excretion), and toxicity evaluation based on ADME. 【Joint research with Dr. Higashisaka】

Nano-Safety Design research related to toxicokinetic analysis and its control

Based on the results of risk analysis of nanomaterial, we will actively promote the use of nanomaterial that are judged to be safe, while for those that are concerned about safety, we attempt to elucidate the mechanism and to control the physicochemical properties of nanomaterial so that its toxicity can be avoided. 【Joint research with Dr. Higashisaka】

Elucidation of the molecular mechanisms of disease based on development of research platform and application for drug discovery

The investigation of the mechanisms of unexpected toxicity caused by therapeutic drugs such as adverse event and drug resistance is urgent issue. We especially focus on how molecular targeted drugs acquire resistance in refractory cancer by means of proteomics and transcriptome method. 【Joint research with Dr. Haga】

Genotoxicity and carcinogenicity of microplastics.

There is increasing attention on the risk analysis of microplastics (small pieces of plastic, less than 5 mm) on human health. We attempt to evaluate the effect of microplastics especially focusing on its genotoxicity and carcinogenicity by using damaged microplastics which exist in environment. 【Joint research with Dr. Haga】

Representative achievements

Yamamoto Y., Tsutsumi Y., Yoshioka Y., Nishibata T., Kobayashi K., Okamoto T., Mukai Y., Shimizu T., Nakagawa S., Nagata S., Mayumi T. : Site-specific PEGlylation of a lysine-deficient TNF-α with full bioactivity., Nature Biotechnology (Nat. Biotech.), 21:546-552, 2003.

Kamada H., Tsutsumi Y., Sato-Kamada K., Yamamoto Y., Yoshioka Y., Okamoto T., Nakagawa S., Nagata S., Mayumi T. : Synthesis of a poly(vinylpyrrolidone-co-dimethyl maleic anhydride) co-polymer and its application for renal drug targeting., Nature Biotechnology (Nat. Biotech.), 21:399-404, 2003.

Mukai Y., Nakamura T., Yoshikawa M., Yoshioka Y., Tsunoda S., Nakagawa S., Yamagata Y., Tsutsumi Y. : Solution of the structure of the TNF-TNFR2 complex., Science Signaling (Sci. Signal.), 3(148), ra83:1-10, 2010.

Yamashita K., Yoshioka Y., Higashisaka K., Mimura K., Morishita Y., Nozaki M., Yoshida T., Ogura T., Nabeshi H., Nagano K., Abe Y., Kamada H., Monobe Y., Imazawa T., Aoshima H., Shishido K., Kawai Y., Mayumi T., Tsunoda S., Itoh N., Yoshikawa T., Yanagihara I., Saito S., Tsutsumi Y. : Silica and titanium dioxide nanoparticles cause pregnancy complications in mice., Nature Nanotechnology (Nat. Nanotechnol.), 6(5):321-328, 2011.

Tsutsumi Y., Yoshioka Y. : Quantifying the biodistribution of nanoparticles., Nature Nanotechnology (Nat. Nanotechnol.), 6(12):755, 2011. (To the Editor)

Hirai T., Yoshioka Y., Izumi N., Ichihashi K., Handa T., Nishijima N., Uemura E., Sagami K., Takahashi H., Yamaguchi M., Nagano K., Mukai Y., Kamada H., Tsunoda S., Ishii K., Higashisaka K., Tsutsumi Y. : Metal nanoparticles in the presence of lipopolysaccharides trigger the onset of metal allergy in mice., Nature Nanotechnology (Nat. Nanotechnol.) , 11(9): 808-16, 2016.

Morishita Y., Yoshioka Y., Takimura Y., Shimizu Y., Namba Y., Nojiri N., Ishizaka T., Takao K., Yamashita F., Takuma K., Ago Y., Nagano K., Mukai Y., Kamada H., Tsunoda S., Saito S., Matsuda T., Hashida M., Miyakawa T., Higashisaka K., Tsutsumi Y. : Distribution of silver nanoparticles to breast milk and their biological effects on breast-fed offspring mice., ACS Nano., 10(9): 8180-91, 2016.

Srivastava S., Nataraj BN., Sekar A., Ghosh S., Bornstein C., Drago-Garcia D., Roth L., Romaniello D., Marrocco I., David E., Gilad Y., Lauriola M., Rotkopf R., Kimchi A., Haga Y., Tsutsumi Y., Mirabeau O., Surdez D., Zinovyev A., Delattre O., Kovar H., Amit I., Yarden Y. : ETS proteins bind with glucocorticoid receptors: relevance for treatment of ewing sarcoma., Cell Reports(Cell Rep.), 29(1): 104-17, 2019.

Matsushita S., Tachibana K., Kusakabe T., Hirayama R., Tsutsumi Y., Kondoh M. : The roadmap to approval under Japan’s two track regulatory system: comparing six regenerative medical products. Cell Stem Cell, 27(4): 515-518, 2020.

Uribe M. L., Dahlhoff M., Batra R. N., Nataraj N. B., Haga Y, Drago-Garcia D., Marrocco I., Ghosh S., Vaknin I., Lebon S., Tsutsumi Y., Choi I., Rueda S. M., Caldas C., Yarden Y.: TSHZ2 is an EGF-regulated tumor suppressor that binds to the cytokinesis regulator PRC1 and inhibits metastasis., Science Signaling (Sci. Signal.), 14(688):eabe6156., 2021.