研究について

広島生命科学研究所の研究

研究所では下記の研究を行っています。

B型肝炎の研究
  • C型肝炎のように完治できるようにする
  • 肝癌ができるメカニズム
C型肝炎の研究
  • ウイルス排除後の発がんのメカニズム
  • 肝癌にならないようにする
MASH、MAFLD(脂肪性肝炎)の研究
  • 肝硬変への進行を防止する
  • 代謝異常(糖尿病、高血圧、高脂肪症、痛風)との関連を解明する
その他の肝疾患の研究
  • 原発性胆汁性胆管炎、自己免疫性肝炎の治療法
  • ウイルソン病の治療法
肝癌の研究
  • 肝癌の新しい治療の研究
  • 肝癌の予防の研究

広島生命科学研究所の業績

1: Makokha GN, Abuduwaili M, Chayama K, Hijikata M. What is the future of Mpox outbreak? Virology. 2025 Jun 27;610:110618. doi: 10.1016/j.virol.2025.110618. Epub ahead of print. PMID: 40609174.

2: Gad SA, Abo Elwafa DA, Hussein SA, Fukano K, Kato T, Shoji I, Chayama K, Muramatsu M, Isogawa M, Wakita T, Merk D, Aly HH. RXR agonist S169 inhibits HBV/HDV entry in vitro by disrupting KIF4-dependent NTCP trafficking. Antiviral Res. 2025 Aug;240:106214. doi: 10.1016/j.antiviral.2025.106214. Epub 2025 Jun 14. PMID: 40523562.

3: Nakayama N, Nakao M, Uchida Y, Ido A, Takikawa Y, Kakisaka K, Kato N, Chayama K, Inoue K, Kasahara M, Terai S, Ohira H, Sakaida I, Takami T, Hasegawa K, Abe M, Shimizu M, Yoshiji H, Genda T, Inui A, Abe R, Takikawa H, Tanaka A, Mochida S. Nationwide survey of patients with acute liver failure and late-onset hepatic failure in Japan seen between 2016 and 2021. Hepatol Res. 2025 Jun;55(6):932-947. doi: 10.1111/hepr.14191. Epub 2025 Apr 15. PMID: 40317595.

4: Shekhtman L, Ishida Y, Tsuge M, Reinharz V, Yamao M, Takahashi M, Tateno C, Uprichard SL, Dahari H, Chayama K. Modeling of hepatitis B virus kinetics and accumulation of cccDNA in primary human hepatocytes. JHEP Rep. 2024 Dec 24;7(4):101311. doi: 10.1016/j.jhepr.2024.101311. PMID: 40236628; PMCID: PMC11997607.

5: Shi Z, Tsuge M, Collier N, Takeuchi Y, Uchida T, Rutter CM, Teraoka Y, Uprichard S, Ishida Y, Tateno C, Ozik J, Dahari H, Chayama K. Modeling of hepatitis B virus infection spread in primary human hepatocytes. bioRxiv [Preprint]. 2025 Feb 7:2025.02.05.636596. doi:10.1101/2025.02.05.636596. PMID: 39975229; PMCID: PMC11838564.

6: Crouchet E, Almeida N, Durand SC, Parnot M, Oudot MA, Giannone F, Gadenne C, Roehlen N, Saviano A, Felli E, Pessaux P, Duong HT, Ohdan H, Aikata H, Chayama K, Baumert TF, Schuster C. A patient-derived HCC spheroid system to model the tumor microenvironment and treatment response. JHEP Rep. 2024 Oct 28;7(2):101252. doi: 10.1016/j.jhepr.2024.101252. PMID: 39897611; PMCID: PMC11782825.

7: Shi Z, Mhlanga A, Ishida Y, Josephson A, Collier NT, Abe-Chayama H, Tateno-Mukaidani C, Cotler SJ, Ozik J, Major M, Feld JJ, Chayama K, Dahari H. Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies. Sci Rep. 2024 Dec 30;14(1):31826. doi:10.1038/s41598-024-83104-0. PMID: 39738554; PMCID: PMC11686243.

8: Makokha GN, Bao H, Hayes CN, Abuduwaili M, Songok E, Hijikata M, Chayama K. The Prevalence and Genotype Distribution of Hepatitis C Virus in Kenya: A Systematic Review and Meta-Analysis. J Epidemiol Glob Health. 2024 Sep;14(3):677-689. doi: 10.1007/s44197-024-00299-1. Epub 2024 Sep 10. PMID:39254917; PMCID: PMC11442939.

9: Mukherji A, Jühling F, Simanjuntak Y, Crouchet E, Del Zompo F, Teraoka Y, Haller A, Baltzinger P, Paritala S, Rasha F, Fujiwara N, Gadenne C, Slovic N, Oudot MA, Durand SC, Ponsolles C, Schuster C, Zhuang X, Holmes J, Yeh ML, Abe-Chayama H, Heikenwälder M, Sangiovanni A, Iavarone M, Colombo M, Foung SKH, McKeating JA, Davidson I, Yu ML, Chung RT, Hoshida Y, Chayama K, Lupberger J, Baumert TF. An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection. Nat Commun. 2024 Aug 29;15(1):7486. doi: 10.1038/s41467-024-51698-8. PMID: 39209804; PMCID: PMC11362569.

10: Crouchet E, Dachraoui M, Jühling F, Roehlen N, Oudot MA, Durand SC, Ponsolles C, Gadenne C, Meiss-Heydmann L, Moehlin J, Martin R, Brignon N, Del Zompo F, Teraoka Y, Aikata H, Abe-Chayama H, Chayama K, Saviano A, Heide D, Onea M, Geyer L, Wolf T, Felli E, Pessaux P, Heikenwälder M, Chambon P, Schuster C, Lupberger J, Mukherji A, Baumert TF. Targeting the liver clock improves fibrosis by restoring TGF-β signaling. J Hepatol. 2025 Jan;82(1):120-133. doi: 10.1016/j.jhep.2024.07.034. Epub 2024 Aug 22. PMID: 39173955.

11: Duehren S, Uchida T, Tsuge M, Hiraga N, Uprichard SL, Etzion O, Glenn J, Koh C, Heller T, Cotler SJ, Oka S, Chayama K, Dahari H. Interferon alpha induces a stronger antiviral effect than interferon lambda in HBV/HDV infected humanized mice. Virus Res. 2024 Nov;349:199451. doi: 10.1016/j.virusres.2024.199451. Epub 2024 Aug 26. PMID: 39168375; PMCID: PMC11446150.

12: Macdonald JK, Taylor HB, Wang M, Delacourt A, Edge C, Lewin DN, Kubota N, Fujiwara N, Rasha F, Marquez CA, Ono A, Oka S, Chayama K, Lewis S, Taouli B, Schwartz M, Fiel MI, Drake RR, Hoshida Y, Mehta AS, Angel PM. The Spatial Extracellular Proteomic Tumor Microenvironment Distinguishes Molecular Subtypes of Hepatocellular Carcinoma. J Proteome Res. 2024 Sep 6;23(9):3791-3805. doi: 10.1021/acs.jproteome.4c00099. Epub 2024 Jul 9. PMID: 38980715; PMCID: PMC11385377.

13: Nakatsuka T, Tateishi R, Sato M, Hashizume N, Kamada A, Nakano H, Kabeya Y, Yonezawa S, Irie R, Tsujikawa H, Sumida Y, Yoneda M, Akuta N, Kawaguchi T, Takahashi H, Eguchi Y, Seko Y, Itoh Y, Murakami E, Chayama K, Taniai M, Tokushige K, Okanoue T, Sakamoto M, Fujishiro M, Koike K. Deep learning and digital pathology powers prediction of HCC development in steatotic liver disease. Hepatology. 2025 Mar 1;81(3):976-989. doi: 10.1097/HEP.0000000000000904. Epub 2024 May 20. PMID: 38768142; PMCID: PMC11825480.

14: Abe-Chayama H, Kawase T, Ichinohe T, Ishida Y, Tateno C, Hijikata M, Chayama K. Hepatitis B virus-specific human stem cell memory T cells differentiate into cytotoxic T cells and eradicate HBV-infected hepatocytes in mice. FEBS Lett. 2024 Jun;598(11):1354-1365. doi: 10.1002/1873-3468.14842. Epub 2024 Apr 9. PMID: 38594179.

15: Qin XY, Shirakami Y, Honda M, Yeh SH, Numata K, Lai YY, Li CL, Wei F, Xu Y, Imai K, Takai K, Chuma M, Komatsu N, Furutani Y, Gailhouste L, Aikata H, Chayama K, Enomoto M, Tateishi R, Kawaguchi K, Yamashita T, Kaneko S, Nagaoka K, Tanaka M, Sasaki Y, Tanaka Y, Baba H, Miura K, Ochi S, Masaki T, Kojima S, Matsuura T, Shimizu M, Chen PJ, Moriwaki H, Suzuki H. Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence. Int J Cancer. 2024 Aug 1;155(3):582-594. doi: 10.1002/ijc.34893. Epub 2024 Feb 21. PMID: 38380807.

16: Toyoda H, Tada T, Uojima H, Nozaki A, Chuma M, Takaguchi K, Hiraoka A, Abe H, Itobayashi E, Matsuura K, Atsukawa M, Watanabe T, Shimada N, Nakamuta M, Kojima M, Tsuji K, Mikami S, Ishikawa T, Yasuda S, Tsutsui A, Arai T, Kumada T, Tanaka Y, Tanaka J, Chayama K. Comparison of six hepatocellular carcinoma prediction models in Japanese patients after sustained virologic response undergoing rigorous surveillance for hepatocellular carcinoma. J Gastroenterol Hepatol. 2024 May;39(5):949-954. doi: 10.1111/jgh.16494. Epub 2024 Jan 30. PMID: 38291715.

17: Toyoda H, Koshiyama Y, Yasuda S, Kumada T, Chayama K, Akita T, Tanaka J. Effect of previous infection with hepatitis B virus on the incidence of hepatocellular carcinoma after sustained virologic response in patients with chronic hepatitis C virus infection. J Viral Hepat. 2024 Mar;31(3):137-142. doi: 10.1111/jvh.13907. Epub 2023 Dec 26. PMID: 38146596.

18: Yamauchi M, Ono A, Amioka K, Fujii Y, Nakahara H, Teraoka Y, Uchikawa S, Fujino H, Nakahara T, Murakami E, Okamoto W, Miki D, Kawaoka T, Tsuge M, Imamura M, Hayes CN, Ohishi W, Kishi T, Kimura M, Suzuki N, Arihiro K, Aikata H, Chayama K, Oka S. Lenvatinib activates anti-tumor immunity by suppressing immunoinhibitory infiltrates in the tumor microenvironment of advanced hepatocellular carcinoma. Commun Med (Lond). 2023 Oct 25;3(1):152. doi: 10.1038/s43856-023-00390-x. PMID: 37880538; PMCID: PMC10600115.

19: Hailegiorgis A, Ishida Y, Collier N, Imamura M, Shi Z, Reinharz V, Tsuge M, Barash D, Hiraga N, Yokomichi H, Tateno C, Ozik J, Uprichard SL, Chayama K, Dahari H. Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics. PLoS Comput Biol. 2023 Aug 3;19(8):e1011309. doi: 10.1371/journal.pcbi.1011309. PMID: 37535676; PMCID: PMC10426918.

20: Uchida T, Imamura M, Hayes CN, Suehiro Y, Teraoka Y, Ohya K, Aikata H, Abe-Chayama H, Ishida Y, Tateno C, Hara Y, Hino K, Okamoto T, Matsuura Y, Aizaki H, Wake K, Kohara M, Liang TJ, Oka S, Chayama K. HBV with precore and basal core promoter mutations exhibits a high replication phenotype and causes ER stress-mediated cell death in humanized liver chimeric mice. Hepatology. 2023 Sep 1;78(3):929-942. doi: 10.1097/HEP.0000000000000335. Epub 2023 Mar 13. PMID: 36896966; PMCID: PMC11519831.

21: Yoshikawa Y, Imamura M, Yamauchi M, Hayes CN, Aikata H, Okamoto W, Miyata Y, Okada M, Hattori N, Sugiyama K, Yoshioka Y, Toratani S, Takechi M, Ichinohe T, Ueda T, Takeno S, Kobayashi T, Ohdan H, Teishima J, Hide M, Nagata Y, Kudo Y, Iida K, Chayama K. Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors. BMC Cancer. 2022 Nov 29;22(1):1232. doi: 10.1186/s12885-022-10327-7. PMID: 36447159; PMCID: PMC9706984.

22: Uchida T, Teraoka Y, Imamura M, Abe-Chayama H, Makokha GN, Hayes CN, Aikata H, Hamamura S, Ishida Y, Tateno C, Shirouzu T, Kawai S, Tanaka Y, Ohdan H, Okada S, Chayama K. A novel cDNA-uPA/SCID/Rag2<sup>-/-</sup> /Jak3<sup>-/-</sup> mouse model for hepatitis virus infection and reconstruction of human immune system. J Viral Hepat. 2023 Mar;30(3):262-272. doi: 10.1111/jvh.13793. Epub 2023 Jan 12. PMID: 36575861.

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