Department of Molecular Pathophysiology, Institute of Advanced Medicine

Outline

The number of patients suffered from diseases such as cancer, infectious diseases, the circulatory diseases and dementia is expected to increase, associated with advancement of aging society in our country. It is necessary to prevent lifestyle-related diseases, to improve and maintain functions for performing social life, and then to realize the extension of healthy life expectancy. Therefore, it is important to elucidate the cause of such diseases.
In our laboratory, we will implement research and education programs necessary for preparing for aging society. We will focus on studying etiology, onset mechanism, prevention, and diagnosis of cancer and infectious diseases by using genome-omics analyses with the single-cell techniques.

The current research themes are as follows:

1. The microenvironment state of the carcinoma tissues is involved in diagnosis and clinical conditions. To observe such microenvironmental states, we will study the diversity of the cancer tissue using single cell gene expression and omics analyses.
2. HBV is a causative agent for cirrhosis, resulting in hepatocellular carcinoma. However, it is not clear how infection with HBV causes such liver diseases. We will study identification of molecules relating to promotion or inhibition of HBV replication, show molecular mechanisms of maintaining latent HBV in cells, and then try to develop antiviral drugs.

Research

Recent Research Results

1. Hashimoto S., Nx1-Seq (Well Based Single-Cell Analysis System), Adv Exp Med Biol., 2019,1129,51-61. doi: 10.1007/978-981-13-6037-4_4.
2. Tsukui, T., Ueha, S., Shichino, S., Hashimoto, S.,? Nakajima, T.,Shiraishi, K., Kihara, M.,? Kiyonari, H., Inagak, Y., Matsushima K. Gli signaling pathway modulates fibroblast activation and facilitates scar formation in pulmonary fibrosis。Biochem Biophys Res Commun., 2019, pii: S0006-291X(19)30879-4. doi: 10.1016/j.bbrc.2019.05.011.
3. Shiraishi, K., Shichino, S., Tsukui, T., Hashimoto, S., Ueha, S., Matsushima, K. Engraftment and proliferation potential of embryonic lung tissue cells in irradiated mice with emphysema. Sci Rep., 2019,9,3657. doi: 10.1038/s41598-019-40237-x.
4. Aoki, H.,?? Ueha, S.,?? Shichino, S., Ogiwara, S., Hashimoto, S., Kakimi, K., Ito, S., Matsushima1, K.,TCR repertoire analysis reveals mobilization of novel CD8+ T cell clones into the Cancer-Immunity Cycle following anti-CD4 antibody administration. Front Immunol., 2019, 9,3185. doi: 10.3389/fimmu.2018.03185.
5. Shiraishi, K., Shichino, S., Ueha, S., Nakajima, T., Hashimoto, S., Yamazaki, S., Matsushima, K., Mesenchymal-epithelial interactome analysis reveals essential factors required for fibroblast-free alveolosphere formation. iScience,2019, 11, 318-333
6. Kawaguchi, K., Wang, Z., Honda, M., Hashimoto, S., hirasaki, T., Okada, H., Orita, N., Shimakami, T., Yamashita, T., Sakai, Y., Mizukoshi, E., Murakami, S., Kaneko, S.,Notch signaling facilitates hepatitis B virus covalently closed circular DNA transcription via cAMP response element-binding protein with E3 ubiquitin ligase-modulation, Sci Rep., 2019,9,1621. doi: 10.1038/s41598-018-38139-5.
7. Shichino, S., Ueha, S., Hashimoto, S., Otsuji, M., Abe, J., Tsukui, T., Deshimaru, S., Nakajima, T., Kosugi-Kanaya, , Shand, FH., Inagaki, Y., Shimano, H., Matsushima, K.,Transcriptome network analysis identifies protective role of the LXR-SREBP-1c axis in murine pulmonary fibrosis. JCI Insight., 2019, 10:. pii: 122163. doi: 10.1172/jci.insight.122163
8. Tabuchi, Y., Hirohashi, Y., Hashimoto, S., Mariya T., Asano, T., Ikeo, K., Kuroda, T., Mizuuchi, M., Murai, A., Uno, S., Kawai, N., Kubo, T., Nakatsugawa, M., Kanaseki, T., Tsukahara, T., Saito, T., Torigoe, T., Clonal analysis revealed functional heterogeneity in cancer stem-like cell phenotypes in uterine endometrioid adenocarcinoma. Exp Mol Pathol., 2019, 106,78-88. doi: 10.1016/j.
9. Souma, K., Shichino, S., Hashimoto, S., Tsukui, T., Nakajima, T., Suzuki, H., Shand, F., Inagaki, Y., Nagase, T., Matsushima, K., Lung fibroblasts express a miR-19a-19b-20a sub-cluster to suppress TGF-β-associated fibroblast activation in murine pulmonary fibrosis. Sci Rep.,2018, 8,16642. doi: 10.1038/s41598-018-34839-0
10. Yoshida, S., Nishimura, N., Yurino, H., Kobayashi, M., Horiguchi, K., Yano, K., Hashimoto, S., Kato, T., *Kato, Y., Differentiation capacities of PS-clusters, adult pituitary stem/progenitor cell clusters located in the parenchymal-niche, of the rat anterior lobe PLOS ONE, 2018 13:e0196029

Main articles(old)

1. Hashimoto, S., Tabuchi, Y., Yurino, H., Hirohashi, Y., Deshimaru, S., Asano, T., Mariya, T., Oshima, K., Takamura, Y., Ukita, Y., Ametani, .A, Kondo N, Monma, N., Takeda, T., Misu, S., Okayama, T., Ikeo, K., Saito, T., Kaneko, S., Suzuki, Y., Hattori, M., Matsushima, K., Torigoe, T., Comprehensive single-cell transcriptome analysis reveals heterogeneity in endometrioid adenocarcinoma tissues. Sci Rep. , 2017 doi:10.1038/s41598-017-14676-3
2. Hashimoto, S., K. Ogoshi, A. Sasaki, J. Abe, W. Qu, Y. Nakatani, B. Ahsan, K.Oshima, F. H. Shand, A. Ametani, Y. Suzuki, S. Kaneko, T. Wada, M. Hattori, S. Sugano, S. Morishita, and K. Matsushima. Coordinated changes in DNA methylation in antigen-specific memory CD4 T cells. J Immunol. , 2013 190:4076-4091
3. Sasaki, S., Mello, C.C., Shimada, A., Nakatani, Y., Hashimoto, S., Ogawa, M., Matsushima, K., Gu, S.G., Kasahara, M., Ahsan, B., Sasaki, A., Saito, T., Suzuki, Y., Sugano, S., Kohara, Y., Takeda, H., Fire, A., and Morishita, S.? Chromatin-associated periodicity in genetic variation downstream of transcriptional start sites. Science , 2009 323:401-404
4. Hashimoto, S., Qu, W., Ahsan, B., Ogoshi, K., Sasaki, A., Nakatani, Y., Lee, Y., Ogawa, M., Ametani, A., Suzuki, Y., Sugano, S., Lee, C.C., Nutter, R.C., Morishita, S., and Matsushima, K. * High-resolution analysis of the 5'-end transcriptome using a next generation DNA sequencer. PLoS One, 2009 4:e4108
5. Hashimoto, S., Suzuki, Y., Kasai, Y., Morohoshi, k., Yamada, T., Sese, J., Morishita, S., Sugano, S., and Matsushima, K.? 5’-end SAGE for the analysis of transcriptional start sites. Nat Biotechnol., 2004 22:1146-1149
6. Hashimoto, S., Nagai, S., Sese, J., Suzuki, T., Obata, A., Sato, T., Toyoda, N., Dong, H.Y., Kurachi, M., Nagahata, T., Shizuno, K.I., Morishita, S., and Matsushima, K.? Gene expression profile in human leukocytes. Blood, 2003 101:3509-3513
7. Hashimoto, S., Komuro, I., Yamada, M., and Akagawa, K.S.? IL-10 inhibits GM-CSF-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages. J Immunol., 2001 167:3619-3625
8. Hashimoto, S., Suzuki, T., Dong, H.-Y., Nagai, S., Yamazaki, N., and Matsushima, K.? Serial analysis of gene expression in human monocyte-derived dendritic cells. PLENARY PAPER, Blood, 1999 94:845-852
9. Hashimoto, S., Suzuki, T., Dong, H.-Y., Yamazaki, N., and Matsushima, K.? Serial analysis of gene expression in human monocytes and macrophages. PLENARY PAPER, Blood, 1999 94:837-844
10. Hashimoto, S. , Yamada, M., Motoyoshi, K., and Akagawa, K.S. Enhancement of macrophage-colony stimulating factor-induced growth and differentiation of human monocytes by interleukin-10. Blood, 1997 89:315-321

Staff introduction

E-mail address: Please put @wakayama-med.ac.jp after blue letters.

Undergraduate

• School of Medicine
  • Message from the Dean
  • List of Medicine
• School of Health and Nursing Science
  • Message from the Dean
• School of Pharmaceutical Sciences
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