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Toxicology and Safety Science(Medical and Health Sciences)

Higashisaka KazumaAssociate professor

Mar 2009: Bachelor of Pharmaceutical Sciences (UOsaka.), May 2009: License to practice pharmacy, Mar 2016: Ph.D. (UOsaka.). Oct 2012: Assistant Professor (Grad. Sch. Pharm. Sci., UOsaka.), Oct 2017: Specially Appointed Lecture (Grad. Sch. Med., UOsaka.), Apr 2021: Associate Professor (Inst. Adv. Co-Creation Stud., UOsaka.), Apr 2026 - present: Associate Professor (Grad. Sch. Pharm. Sci., UOsaka.).

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., 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.

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.

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.

Sakahashi Y., Higashisaka K., Isaka R., Izutani R., Seo J., Furuta A., Yamaki-Ushijima A., Tsujino H., Haga Y., Nakashima A., Tsutsumi Y. : Silver nanoparticles suppressed forskolin-induced syncytialization in BeWo cells., Nanotoxicology, 16(9-10): 883-94, 2022.

Yamaguchi S., Isaka R., Sakahashi Y., Tsujino H., Haga Y., Higashisaka K., Tsutsumi Y. : Silver nanoparticles suppress retinoic acid–induced neuronal differentiation in human-derived neuroblastoma SH-SY5Y cells., ACS Appl. Nano Mater., 5: 19025-34, 2022.

Kitahara G., Higashisaka K., Nakamoto Y., Yamamoto R, Okuno W., Serizawa M., Sakahashi Y., Tsujino H., Haga Y., Tsutsumi Y. : Valproic acid induces HIF-1α-mediated CGB expression elevation and glucose uptake suppression in BeWo cell., J. Toxicol. Sci., 49(2): 69-77, 2024.

Kobayashi J., Higashisaka K., Muranaka M., Xie Y., Okuno W., Haga Y., Tsutsumi Y. : Localization of silica nanoparticles to lysosome causes lysosomal dysfunction in JEG-3 cell., Biochem. Biophys. Res. Commun., 736: 150488, 2024.

Saeki Y., Higashisaka K., Izutani R., Seo J., Miyaji K., Haga Y., Tsutsumi Y. : Orally administered silver nanoparticles are absorbed and migrate to the testes in mice., ACS Nanosci. Au, 4(5): 317-21, 2024.

Yamamoto R., Higashisaka K., Sakai R., Nakamoto Y., Serizawa M., Haga Y., Tsutsumi Y. : Silica nanoparticles reduce fetal weight in mice and induce an inflammatory response in human extravillous trophoblast cells., Biochem. Biophys. Res. Commun., 788: 152803, 2025.