Gifu, Japan

Hygienic Chemistry and Molecular Toxicology

Research Interests

We are working on two main themes, “toxicity evaluation of chemicals for safe use (including remediation of chemical-contaminated environment)” and “disease prevention by active use of chemicals (including health food, preventive medicine, and so on.)”. Toxicity of chemicals, mainly on developmental toxicity, immunotoxicity, endocrine disruption, is investigated with using molecular biological techniques and transgenic animals“ Endocrine disrupting effect of organotin compounds and their molecular mechanism” is one of our main studies, Organotin compounds (TBT and TPT) used in antifouling paints for ships have been known to cause reproductive failure called “imposex” in most marine gastropods. However, the mechanism remained unclear. Recently, we found that these organotins act as powerful agonists for the retinoid X receptor (RXR), and RXR is a key target of organotins-induced imposex. In addition, we found that these organotins also act as powerful peroxisome proliferator-activated receptor (PPAR)γ agonists. Our research results suggest that organotin compounds induce various toxicities via RXR and/or PPARγ signaling pathway in various species.

Research Objectives
  1. Studies on endocrine disrupting chemicals and mechanism of their actions on sex development in mammals
  2. Studies on analysis of factors on obesity repression in mammals and effect of chemicals on the factors
  3. Development of analytical methods on environment dynamics and detoxification treatment methods of hazardous chemicals
  4. Elucidation of modifying mechanism of immune function by chemicals and establishment of evaluating methods for chemicals inducing allergic response
Research Results
  1. Hiromori Y., Yui H., Nishikawa J., Nagase H., Nakanishi T., Organotin Compounds Cause Structure-Dependent Induction of Progesterone in Human Choriocarcinoma Jar Cells, J. Steroid Biochem. Mol. Biol., 155, 190­­­­­­­­­–198 (2016).
  2. Harada S., Hiromori Y., Nakamura S., Kawahara K., Fukakusa S., Maruno T., Noda M., Uchiyama S., K. Fukui, Nishikawa J., Nagase H., Kobayashi Y., Yoshida T., Ohkubo T., Nakanishi T., Structural Basis for PPARc Transactivation by Endocrine-disrupting Organotin Compounds. Scientific Reports, 5, 8520 (2015)
  3. Hiromori Y, Aoki A, Nishikawa J, Nagase H, Nakanishi T: Transactivation of the Human Retinoid X Receptor by Organotins: Use of Site-directed Mutagenesis to Identify Critical Amino Acid Residues for Organotin-induced Transactivation. Metallomics., 7, 1180­­­­­­­­­–1188 (2015).
  4. Gutierrez-Mazariegos J., Kumar Nadendla E., Lima D., Kane M., Nishikawa J., Hiromori Y., Nakanishi T., Santos MM., Castro LFC., Bourguet W., Schubert M., Laudet V., A Mollusk Retinoic Acid Receptor (RAR) Ortholog Sheds Light on the Evolution of Ligand Binding, Endocrinology, 155, 4275-4286 (2014)
  5. Ido A.,Ishihara S., Kume A., Nakanishi T., Monguchi Y., Sajiki H., NagaseH., Practical Method for PCB Degradation Using Pd/C–H2–Mg System, Chemosphere, 90, 57-64 (2013).
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