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Faculty Members


Toxicology and Safety Science(Medical and Health Sciences)

Higashisaka KazumaAssociate professor

Mar 2009: Bachelor of Pharmaceutical Science (Osaka Univ.), May 2009: License to practice pharmacy, Mar 2016: Ph.D. (Osaka Univ.). Oct 2012: Assistant Professor (Grad. Sch. Pharm. Sci., Osaka Univ.), Oct 2017: Specially Appointed Lecture (Grad. Sch. Med., Osaka Univ.), Apr 2021 - present: Associate Professor (Inst. Adv. Co-Creation Stud., Osaka Univ).

Research theme

Placental toxicity analysis of chemical substances and construction of evaluation system

The main target in reproductive toxicity test of chemical substances is the effect on the fetus, but the maternal placental toxicity is not evaluated very much. Placenta is essential for the establishment and maintenance of pregnancy and for the healthy growth of the fetus, and thus understanding the toxicity to the placenta is important in assessing the reproductive toxicity of chemical substances. Here, we analyze their effects on placental kinetics <ADME> and placental formation <toxicity>, and aim to develop a placental toxicity evaluation system for chemical substances in consideration of the toxicological mechanism.

Elucidation and control of particulate response to next-generation health effects

To prevent health effects in infancy at an early stage, it is important to improve the growth and environment in the fetal period and to prevent the onset of health effects. Therefore, in this study, from the viewpoint of exposure to the fine particles that are overflowing around us, by trying to understand the effects of fine particle exposure on the health of the next generation and elucidate the mechanism, we aim to establish preventive and therapeutic methods for the next generation of health effects.

Representative achievements

Higashisaka K., Yoshioka Y., Yamashita K., Morishita Y., Fujimura M., Nabeshi H., Nagano K., Abe Y., Kamada H., Tsunoda S., Yoshikawa T., Itoh N., Tsutsumi Y. : Acute phase proteins as biomarkers for predicting the exposure and toxicity of nanomaterials. Biomaterials, 32(1): 3-9, 2011.

Higashisaka K., Yoshioka Y., Yamashita K., Morishita Y., Pan H., Ogura T., Nagano T., Kunieda A., Nagano K., Abe Y., Kamada H., Tsunoda S., Nabeshi H., Yoshikawa T., Tsutsumi Y. : Hemopexin as biomarkers for analyzing the biological responses associated with exposure to silica nanoparticles. Nanoscale Res. Lett., 7(1): 555, 2012.

Higashisaka K., Fujimura M., Taira M., Yoshida T., Tsunoda S., Baba T., Yamaguchi N., Nabeshi N., Yoshikawa T., Nasu M., Yoshioka Y., Tsutsumi Y. : Asian dust particles induce macrophage inflammatory responses via mitogen-activated protein kinase activation and reactive oxygen species production., J. Immunol. Res., 2014: 856154, 2014.

Higashisaka K., Kunieda A., Iwahara Y., Tanaka K., Nagano K., Mukai Y., Kamada H., Tsunoda S., Yoshioka Y., Tsutsumi Y. : Neutrophilia due to silica nanoparticles induces release of double-stranded DNA., J. Nanomedic. Nanotechnol., 5: 236, 2014.

Higashisaka K., Nakashima A., Iwahara Y., Aoki A., Nakayama M., Yanagihara I., Lin Y., Nagano K., Tsunoda S., Saito S., Yoshioka Y., Tsutsumi Y. : Neutrophil depletion exacerbates pregnancy complications, including placental damage, induced by silica nanoparticles in mice., Front. Immunol., 9: 1850, 2018.

Lin Y., Higashisaka K., Shintani T., Maki A., Hanamuro S., Haga Y., Maeda S., Tsujino H., Nagano K., Fujio Y., Tsutsumi Y. : Progesterone receptor membrane component 1 leads to erlotinib resistance, initiating crosstalk of Wnt/β-catenin and NF-κB pathways, in lung adenocarcinoma cells., Sci. Rep., 10(1): 4748, 2020.

Maki A., Lin Y., Aoyama M., Sato K., Gao JQ., Tsujino H., Nagano K., Higashisaka K., Tsutsumi Y. : Silver nanoparticles induce DNA hypomethylation through proteasome-mediated degradation of DNA methyltransferase 1., Biol. Pharm. Bull, 43(12): 1924-30, 2020.

Higashisaka K., Takeya S., Kamada H., Obana M., Maeda M., Kabayama M., Yamamoto K., Ishida N., Isaka R., Tsujino H., Nagano K., Tomiyama N., Rakugi H., Fujio Y., Kamide K., Tsutsumi Y. : Identification of biomarkers of chronic kidney disease among kidney-derived proteins., Clin. Proteomics, 19(1): 3, 2022.

Yang L., Higashisaka K., Shimoda M., Haga Y., Sekine N., Tsujino H., Nagano K., Shimazu K., Tsutsumi Y. : Alpha-crystallin B chains in trastuzumab-resistant breast cancer cells promote endothelial cell tube formation through activating mTOR., Biochem. Biophys. Res. Commun., 588: 175-81, 2022.

Eto S., Higashisaka K., Koshida A., Sato K., Ogura M., Sakurai M., Tsujino H., Nagano K., Tsutsumi Y. : Amorphous silica nanoparticles exacerbate hepatic damage through the activation of acquired cell-mediated immunity., Nano Ex., 3: 015002, 2022.