Department of Cellular and Molecular Biology, Nagasaki University Graduate School of Biomedical Sciences



  • Is the protein-only hypothesis (prion hypothesis) valid?
  • Development of diagnostic tests for prion diseases
  • Drug discovery for human prion diseases
  • Development of disinfection methods for human prion diseases
  • Epidemiological studies on human prion diseases
  • In silico drug discovery for viral diseases


  • 1925: Established as the Department of Bacteriology by Professor Toshio Abe
  • 1932: Professor Tatsuo Naitoh assumes leadership of the Department of Bacteriology
  • 1945: WWII ends with the atomic bombing of Nagasaki, resulting in the total destruction of the Medical School
  • 1946: The Department of Bacteriology is started anew by Professor Giyu Aoki
  • 1971: Professor Tsutomu Miyamoto takes over leadership and initiates research on prion diseases
  • 1998: Professor Shigeru Katamine assumes the leadership of the department
  • 2009: Professor Noriyuki Nishida assumes leadership of the Department of Cellular and Molecular Biology

Our story…

The history of prion research in our department at Nagasaki University dates back to the late seventies, when the Department of Bacteriology was under the leadership of Professor Tsutomu Miyamoto. Professor Miyamoto commenced research into Gerstmann-Sträussler-Scheinker syndrome (GSS), a genetic human prion disease that primarily affects cerebellar function. It was the first transmissible spongiform encephalopathy (TSE) in humans for which a mutation in the gene encoding prion protein (PrP) had been discovered. In 1979, Professor Jun Tateishi, a renowned Neuropathology professor at Kyushu University, successfully transmitted GSS prion to mice and named the resulting strain “Fukuoka-1”. He provided a sample of the infected mouse brain to Professor Miyamoto, whose team subsequently conducted detailed analyses with the aim of elucidating the natural transmission route and growth patterns in various organs following transmission using Fukuoka-1 strain-infected mice.

In 1982, Professor Stanley Pruisner in UCSF described his “protein-only hypothesis”, which proposed that prion diseases are caused by the misfolding of prion proteins, thereby inducing normal proteins to adopt the abnormal conformation. Soon after that, the gene for the prion protein was identified and several different groups started making gene-knockout mice to elucidate the role of the protein in prion diseases.

In 1996, a postgraduate student at our department, Dr. Suehiro Sakaguchi, who subsequently became Professor at Tokushima University, established a line of PrP-knockout mice, which he used to confirm the essential role of the gene in maintenance of cerebellar Purkinje cells. This finding was published in the journal Nature in 1996.

In 2001, while the department was under the leadership of Professor Katamine, BSE (bovine spongiform encephalopathy) was confirmed in cattle for the first time in Japan. Professor Katamine joined the national BSE research project to study various aspects of prion diseases, including drugs for prion, strain diversity, and immune response against prion.

In 2005, a collaboration between Dr Noriyuki Nishida, at the time an Assistant Professor at the Department, and Professor Laura Manuelidis of Yale Medical School, led to the publication in the journal Science of a paper on the "interference" between different prion strains. A separate collaboration, in which Dr Nishida joined forces with Professor Kazuo Kuwata of Gifu University, resulted in the publication in 2007, in the Proceedings of the National Academy of Sciences (PNAS), of a paper on novel compounds capable of binding to PrP and inhibiting the conversion process.

In 2009, Professor Nishida took over from Professor Katamine, following the latter’s departure to become President of Nagasaki University. Professor Nishida and two then Associate Professors, Dr. Ryuichiro Atarashi (currently Professor at the Department of Infectious Diseases, Miyazaki University) and Dr. Katsuya Satoh (now Professor of the Department of Health Sciences at Nagasaki University), together established a novel and highly sensitive diagnostic method, the RT-QuiC, and a paper on this work was published in the journal Nature Medicine in 2011.

The RT-QuiC has gone on to become the world-standard test for diagnosing human prion diseases.

In recent years, the department has started using RT-QuiC to screen cadavers donated to the University for anatomical practice, with the aim of preventing any potential accidental transmission to students and staff. In only the second year of the program we identified a previously undiagnosed prion-positive cadaver. Associate Professor Takehiro Nakagaki published a report on this finding in the New England Journal of Medicine in 2022.

In addition, our department is currently involved in various other projects, including iPS models for prion infection, liquid-liquid phase separation of prion protein, and drug discovery for prion diseases.

Overall, Nagasaki University's Department of Cellular and Molecular Biology has a long and illustrious history of contributions to the field of prion research, including significant findings, collaborative studies, and the development of diagnostic methods, and continues to be actively involved in research on prion diseases and other related areas.

Over the years we have also conducted research on viruses such as HTLV-1, human influenza virus, JC virus, and SARS-CoV-2.

Publications in major scientific journals

  • Sakaguchi S, Katamine S, Nishida N, Moriuchi R, Shigematsu K, Sugimoto T, Nakatani A, Kataoka Y, Houtani T, Shirabe S, Okada H, Hasegawa S, Miyamoto T, Noda T. Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Nature. 1996 Apr 11;380(6574):528-31. doi: 10.1038/380528a0.

  • Nishida N, Katamine S, Manuelidis L. Reciprocal interference between specific CJD and scrapie agents in neural cell cultures. Science. 2005 Oct 21;310(5747):493-6. doi: 10.1126/science.1118155.

  • Atarashi R, Satoh K, Sano K, Fuse T, Yamaguchi N, Ishibashi D, Matsubara T, Nakagaki T, Yamanaka H, Shirabe S, Yamada M, Mizusawa H, Kitamoto T, Klug G, McGlade A, Collins SJ, Nishida N. Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion. Nat Med. 2011 Feb;17(2):175-8. doi: 10.1038/nm.2294.

  • Ishibashi D, Homma T, Nakagaki T, Fuse T, Sano K, Satoh K, Mori T, Atarashi R, Nishida N. Type I interferon protects neurons from prions in in vivo models. Brain. 2019 Apr 1;142(4):1035-1050. doi: 10.1093/brain/awz016.

  • Yamaguchi K, Kamatari YO, Ono F, Shibata H, Fuse T, Elhelaly AE, Fukuoka M, Kimura T, Hosokawa-Muto J, Ishikawa T, Tobiume M, Takeuchi Y, Matsuyama Y, Ishibashi D, Nishida N, Kuwata K. A designer molecular chaperone against transmissible spongiform encephalopathy slows disease progression in mice and macaques. Nat Biomed Eng. 2019 Mar;3(3):206-219. doi: 10.1038/s41551-019-0349-8.

  • Hermann P, Appleby B, Brandel JP, Caughey B, Collins S, Geschwind MD, Green A, Haïk S, Kovacs GG, Ladogana A, Llorens F, Mead S, Nishida N, Pal S, Parchi P, Pocchiari M, Satoh K, Zanusso G, Zerr I. Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. Lancet Neurol. 2021 Mar;20(3):235-246. doi: 10.1016/S1474-4422(20)30477-4.

  • Nakagaki T, Kaneko M, Satoh K, Murai K, Saiki K, Matsumoto G, Ogami-Takamura K, Ikematsu K, Akagi A, Iwasaki Y, Tsurumoto T, Nishida N. Detection of Prions in a Cadaver for Anatomical Practice. N Engl J Med. 2022 Jun 9;386(23):2245-2246. doi: 10.1056/NEJMc2204116.