TOP > DEPARTMENTS > DEPARTMENT OF CLINICAL MEDICINE
Fusako Usuki, M.D.
  Director of Department of Clinical Medicine
  Director of Research Coordination,
  Specialty: Clinical Neurology, Molecular medicine for pathogenesis and therapeutics

  • I am not only involved in medical care for patients with Minamata disease as a neurologist but also have an interest in basic research from a clinical viewpoint. Currently, I am conducting basic research using biochemical and molecular biological approaches with cells and animal models in order to uncover the molecular pathomechanism for methylmercury toxicity. I hope that these results will aid in determining suitable molecular targets for therapy and protection, and in solving the clinical pathophysiological problems.
  • Hobbies: gardening, classical music
Subjects of study and affair
  Project research
  • Basic research on the protection and treatment of methylmercury intoxication (collaborator)
  • Clinical research on assessment of brain function and treatment for patients with Minamata disease (collaborator)

  Basic research
  • Study on MeHg-induced changes in genetic expression, its effect on pathological condition, and the protection against methylmercury intoxication (representative)
  • Research on selective cytotoxicity and factors determining individual sensitivity of methylmercury (collaborator)

  Affairs
  • Practice of rehabilitation for patients with Minamata disease and transmission of information on care and rehabilitation (representative)

  Committee
  • Group Leader Committee (group leader)
  • Research Ethics Committee (organizer)
  • COI Committee (group leader)
  • Human Sample Handling Committee (group leader)

Study groups
  • Study group on Pathomechanisms
  • Working group on Clinical Medicine
Research achievements
  ・・elected publications・・BR>   [Original article]
  • Usuki F, Fujimura M, Yamashita A (2017) Endoplasmic reticulum stress preconditioning modifies intracellular mercury content by upregulating membrane transporters. Scientific Reports 7: 12390. doi:10.1038/s41598-017-09435-3.
  • Fujimura M, Usuki F (2017) Site-specific neural hyperactivity via the activation of MAPK and PKA/CREB pathways triggers neuronal degeneration in methylmercury-intoxicated mice. Toxicol Lett. 271: 66-73. doi: 10.1016/j.toxlet. 2017. 03.001.
  • Takahashi T, Fujimura M, Koyama M, Kanazawa M, Usuki F, Nishizawa M, Shimohata T (2017) Methylmercury causes blood brain barrier damage in rats via upregulation of vascular endothelial growth factor expression. PLoS One 12(1):e0170623. doi: 10.1371/journal. pone. 0170623.
  • Usuki F, Tohyama S (2016) Three case reports of successful vibration therapy of the plantar fascia for spasticity due to cerebral palsy-like syndrome, fetal-type Minamata disease. Medicine 95 (15) e3385. doi: 10.1097/MD.0000000000003385.
  • Fujimura M, Usuki F, Cheng J, Zhao W (2016) Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum. Toxicol Appl Pharm 298: 1-8.
    http://www.ncbi.nlm.nih.gov/pubmed/26965727
  • Fujimura M, Usuki F (2015) Low level of methylmercury inhibits neural progenitor cell proliferation through the upregulation of glycogen synthase kinase 3ﾎｲ and subsequent degradation of cyclin E in rats. Toxicol Appl Pharm 288:19-25. doi: 10.1016/ j.taap.2015.07.006.
    http://www.ncbi.nlm.nih.gov/pubmed/26184774
  • Usuki F, Fujimura M (2015) Decreased plasma thiol antioxidant barrier and selenoproteins as potential biomarkers for ongoing methylmercury intoxication and an individual protective capacity Arch Toxicol 2015; doi:10.1007/s00204-015-1528-3
  • Tohyama S, Usuki F (2015) Occupational therapy intervention to inspire self-efficacy in a patient with spinal ataxia and visual disturbance. BMJ Case Reports 2015; doi:10.1136/bcr-2014- 208259
    http://www.ncbi.nlm.nih.gov/pubmed/25666249
  • Fujimura M, Usuki F (2015) Methylmercury causes neuronal cell death through the suppression of TrkA pathway: in vitro and in vivo effects of the TrkA pathway activators. Toxicol Appl Pharm 282(3):259-66.
    http://www.ncbi.nlm.nih.gov/pubmed/25545984
  • Nakamura M, Hachiya N, Murata K, Nakanishi I, Kondo T, Yasutake A, Miyamoto K, Han Ser P, Omi S, Furusawa H, Watanabe C, Usuki F, Sakamoto M (2014) Methylmercury Exposure and Neurological Outcomes in Taiji residents accustomed to consuming whale meat. Environment International 68:25-32.
    http://www.ncbi.nlm.nih.gov/pubmed/24685489
  • Fujimura M, Usuki F (2014) Low in situ expression of antioxidative ] enzymes in rat cerebellar granular cells susceptible to methylmercury. Arch. Toxicol 88: 109-113. doi: 10.1007/s. 00204- 013-1089-2.
    http://www.ncbi.nlm.nih.gov/pubmed/23832 298
  • Usuki F, Yamashita A, Shiraishi T, Shiga A, Onodera O, Higuchi I, Ohno S (2013) Inhibition of SMG-8 ameliorates the mutant phenotype exacerbated by nonsense-mediated mRNA decay without cytotoxicity. Proc Natl Acad Sci 110 (37): 15037-15042. doi: 10.1073/pnas.1300654110
    http://www.ncbi.nlm.nih. gov/pubmed/23983263
  • Usuki F, Fujimura M, Yamashita A (2013) Endoplasmic reticulum stress preconditioning attenuates methylmercury-induced cellular damage by inducing favorable stress responses. Scientific Reports 3:2346:DOI:10.1038/srep02346
    http://www.ncbi.nlm.nih.gov/pubmed/23907635
  • Fujimura M, Usuki F (2012) Differing effects of toxicants
    (methylmercury, inorganic mercury, lead, amyloid and rotenone) on cultured rat cerebrocortical neurons: expression of Rho proteins associated with neurotoxicity. Toxicol Sci 126:506-14.
    PubMed
  • Usuki F, Tohyama S (2011) Vibration therapy of the plantar fascia improves spasticity of the lower limbs of a patient with fetal-type Minamata disease in the chronic stage.
               BMJ Case Reports doi:10.1136/bcr.08.2011.4695
  • Usuki F, Yamashita A, Fujimura M (2011) Methylmercury-induced relative selenium deficiency causes oxidative stress through its posttranscriptional effect. J Biol Chem 286: 6641-6649.
    PubMed
    ・翫€€Rated in Faculty of 1000 Bioogy (Value 8, Must Read)
  • Fujimura M, Usuki F, Kawamura M, Izumo S (2011) Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure. Toxicol Appl Pharmacol 250: 1-9.
    PubMed
  • Fujimura M, Usuki F, Sawada M, Takashima A (2009) Methylmercury induces neuropathological changes with tau hyperphosphorylation mainly through the activation of the c-jun N-terminal kinase pathway in the cerebral cortex, but not in the hippocampus of the mouse brain. Neurotoxicology 30: 1000-1007.
    PubMed
  • Fujimura M, Usuki F, Sawada M, Rostene W, Godefroy D, Takashima A (2009) Methylmercury exposure downregulates the expression of Racl, leads to neuritic degeneration and ultimately apoptosis in cerebrocortical neurons. Neurotoxicology 30:16-22.
    PubMed
  • Usuki F, Fujita E, Sasagawa N (2008) Methylmercury activates ASK1/JNK signaling pathways, leading to apoptosis due to both mitochondria- and endoplasmic reticulum (ER)-generated processes in myogenic cell lines. NeuroToxicology 29:22-30.
    PubMed
  • Usuki F, Yamashita A, Kashima I, Higuchi I, Osame M, Ohno S (2006) Specific inhibition of nonsense-mediated mRNA decay components, SMG-1 or Upf1, rescues the phenotype of Ullrich窶冱 disease fibroblasts. Molecular Therapy 14: 351-60.
    PubMed
    Sako Y, Usuki F, Suga H (2006) A novel therapeutic approach for
    genetic diseases by introduction of suppressor tRNA.
    Nucleic Acids Symposium (Ser) 50: 239-40.
  • Usuki F, Yamashita A, Higuchi I, Ohnishi T, Shiraishi T, Osame M, Ohno S (2004) Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich窶冱縲€disease. Ann Neurol 55:740-744.
    PubMed
  • Usuki F*, Yasutake A, Umehara F, Higuchi I (2004) Beneficial effects of mild lifelong dietary restriction on skeletal muscle: prevention of age-related mitochondrial damage, morphological changes, and vulnerability to a chemical toxin. Acta Neuropathol 108:1-9.
    PubMed
  • Yasuda Y, Liya Q, Matsuyama A, Usuki F, Yasutake A, Aramaki R, Yamaguchi M, Xiaolie L, Li L, Mei AL (2004) Survey of environmental pollution by mercury derived from a chemical factory drain in Guizhou, China. Materials Geoenviron 51: 321-325.
  • Usuki F, Yasutake A, Umehara F, Tokunaga H, Matsumoto M, Eto K, Ishiura S, Higuchi I (2001) In vivo protection of a water-soluble derivative of vitamin E, Trolox, against methylmercury-intoxication in the rat. Neurosci Lett 304:199-203.
    PubMed
  • Usuki F, Yasutake A, Matsumoto M, Higuchi I (2001) Chronic low-dose methylmercury administration decreases mitochondrial enzyme activities and induces myopathic changes in rats. J Health Science 47: 162-167.
    Takahashi N, Sasagawa N, Usuki F, Kino Y, Kawahara H, Sorimachi H, Maeda T, Suzuki K, Ishiura S (2001) Coexpression of the CUG- binding protein reduces DM protein kinase expression in COS cells. J Biochem 130: 581-7.
  • Usuki F and Maruyama K (2000) Ataxia caused by mutations in the α-tocopherol transfer protein gene. J Neurol Neurosurg Psychiatr 69: 254-256.
    PubMed
  • Usuki F, Takahashi N, Sasagawa N, Ishiura S (2000) Differential signaling pathways following oxidative stress in mutant myotonin protein kinase cDNA-transfected C2C12 cell lines. Biochem
    Biophys Res Comm     267: 739-743.
    PubMed
  • Usuki F and Ishiura S (1998) Expanded CTG repeats in myotonin protein kinase increases oxidative stress. NeuroReport 9: 2291-2296.
    PubMed
  • Usuki F, Yasutake A, Matsumoto M, Umehara F, Higuchi I (1998) The effect of methylmercury on skeletal muscle: a histopathological study. Toxicol Lett 94: 227-232.
    PubMed
  • Kameda N. Ueda H, Ohno S, Shimokawa M, Usuki F, Ishiura S, Kobayashi T (1998) Developmental regulation of myotonic dystrophy protein kinase in human muscle cells in vitro.
    Neuroscience 85; 311-322.
    PubMed
  • Usuki F, Ishiura S, Saitoh N, Sasagawa N, Kuzume H, Maruyama K, Sorimachi H, Terao T, Suzuki K (1997) Expanded CTG repeats in myotonin protein kinase supprresses myogenic differentiation. NeuroReport 8: 3749-3753.
    PubMed
  • Usuki F, Ishiura S, Sasagawa N, Sorimachi H, Suzuki K, Shimizu T, Terao T (1995) Up-regulation of dystrophin mRNA by exposure to dibutyryl cAMP in the C2C12 muscle line. Biochem Biophys Res Comm 210:654-659.
  • Usuki F, Takenaga S, Higuchi I, Kashio N, Nakagawa M, Osame M (1994) Morphological findings in biopsied skeletal muscle and cultured fibroblasts from a female patient with Danon's disease (lysosomal glycogen storage disease without acid maltase deficiency). J Neurol Sci 127:54-60.
  • Usuki F, Ohtani H, Okadome T, Shinmyouzu K, Maruyama I, Osame M (1991) Immunocytochemical study on endothelial markers with the cerebral vessel from a patient with familial moyamoya disease. Thromb Haemost 65:335-338.
  • Usuki F, Higuchi I, Soejima Y, Hattori M, Maruyama I, Osame M (1991) Human acid maltase-deficient myogenic cell transformation with origin-defective SV 40: characterization of a cloned line. Muscle Nerve 14:245-252.
  • Kashio N, Usuki F, Akamine T, Nakagawa S, Higuchi I, Nakahara K, Okada A, Osame M, Murata F (1991) Cardiomyopathy, mental retardation, and autophagic vacuolar myopathy---abnormal MRI findings in the head--- J Neurol Sci 105:1-5.
  • Usuki F, Nakazato O, Osame M, Igata A (1989) Hyperestrogenemia in neuromuscular diseases. J Neurol Sci 89:189-197.
  • Kitajima I, Kuriyama M, Usuki F, Izumo S, Osame M, Suganuma T, Murata F, Nagamatsu K (1989) Nasu-Hakola disease (membranous lipodystrophy) Clinical, histopathological and biochemical studies of three cases. J Neurol Sci 91:35-52.
  • Higuchi I, Nonaka I, Usuki F, Ishiura S, Sugita H (1987) Acid maltase deficiency in the Japanese quail; early morphological event in skeletal muscle. Acta Neuropathol 73:32-37.
  • Usuki F, Ishiura S, Nonaka I, Sugita H (1988) ﾎｱ-Glucosidase isoenzymes in normal and acid maltase-deficient skeletal muscles. Muscle Nerve 11:365-371.
  • Usuki F, Ishiura S, Higuchi I, Sugita H (1988) Reappearance of embryonic neutral ﾎｱ-glucosidase isoenzyme in acid maltase-deficient muscle of Japanese quail. Exp Neurol 100:394-402.
  • Usuki F, Ishiura S, Sugita H (1986) Developmental study of ﾎｱ- glucosidases in Japanese quails with acid maltase deficiency. Muscle Nerve 9:537-543.
  • Usuki F, Ishiura S, Sugita H (1986) Isolation and characterization of three ﾎｱ-glucosidases from the Japanese quail. J Biochem 99:985-988.

  [Review article]
  • Usuki F (2014) Formally adopted 窶廴inamata Convention on Mercury窶・ 縲€縲€Igaku no Ayumi 251 (11): 1078-9.
  • Usuki F (2014) Mercury. Neurologic Syndrome (V) (Second edition). pp. 615-618.
  • Usuki F and Sakamoto M (2014) Methylmercury intoxication in fetuses.縲€Neurologic Syndrome (IV) (Second edition). pp. 819-822.
  • Usuki F and Fujimura M (2012) Effects of methylmercury on cellular signal transduction systems. Methylmercury and Neurotoxicology Current Topics in Neurotoxicity, 2012, eds. Aschner M and Ceccatteli S, vol.2, 229-240, Springer. DOI:10. 1007/978-1-4614-2383-6_12
  • Usuki F, Yamashita A (2010) Nonsense-mediated mRNA decay (NMD)-associated diseases. Saibou kougaku. 29 (2):155-160.
  • Yamashita A, Usuki F (2010) mRNA surveillance: molecular mechanism and function. Jikken Igaku pp.134-141.
  • Yamashita A, Usuki F (2009) mRNA surveillance approaches the clinic・・B>Tanpakushitu Kakusan Koso. 54 (16):2219-2225.
  • Usuki F (2007) Neurotoxicant 窶廴ercury窶・ Clinical Neuroscience 25: 877-880.
  • Usuki F (2006) Methylmercury-induced oxidative stress and neuronal cell death. Igaku no Ayumi pp. 431- 4.
  • Usuki F (2006) Specific inhibition of nonsense-mediated mRNA decay has the potential to rescue the phenotype of muscular dystrophy. Rinsho Shinkeigaku 46(11):939-41.
Research by the external fund
  1. Ministry of education, science, sports and culture, grant-in aid for scientific research, 25460402, 2013-2015, Japan (representative)
  2. Ministry of education, science, sports and culture, grant-in aid for scientific research, 24659426, 2012-2013, Japan (collaborator)
  3. Ministry of education, science, sports and culture, grant-in aid for scientific research, 23590167, 2011-2013, Japan (collaborator)
  4. Ministry of education, science, sports and culture, grant-in aid for scientific research, 18590969, 2008-2010, Japan (representative)
  5. Ministry of education, science, sports and culture, grant-in aid for scientific research, 20590135, 2008-2010, Japan (collaborator)
  6. Ministry of education, science, sports and culture, grant-in aid for scientific research, 18590969, 2006-2007, Japan (representative)
The main history, academic background, degree, and citation etc
  • Doctor of Medicine, Neurology specialist
  • Graduated from faculty of medicine, Kagoshima University
    Past history: 3rd Department of Internal Medicine in Kagoshima University, Researcher in National Institute of Neuroscience, Assistant professor in Kagoshima University, Lecturer in Dept. Clinical Neurology in Teikyo University in Tokyo
  • Visiting associate professor in Kumamoto University (2000-2006)
  • Council member of Japanese Society of Neurology (2000-2011)
  • Director, Department of Clinical Medicine in NIMD(2012竏・
  • Director, Research Coordination in NIMD (2013竏・
  • Visiting professor in Kumamoto prefectural University (2014 竏・