Senior Fellow / Kazuhiro Shigemto, M.D.,Ph.D.

Senior Fellow :
Kazuhiro Shigemoto, M.D.,Ph.D.
Researcher:
Katsumi Kawano,Ph.D.
Research Assistants:
Sachiko Kurihara, Satomi Iwata, Ayaka Minami, Yumi Horie

1. Neuromuscular synapse dysfunction occurs even before the onset of neuromuscular diseases and sarcopenia (age-related muscle atrophy). Activation of MuSK (muscle-specific kinase) protein at neuromuscular synapses has been shown to promote neuromuscular synapse regeneration and inhibit the progression of sarcopenia and neuromuscular intractable diseases. There is a need for a blood diagnostic biomarker useful for both drug discovery research and clinical diagnosis. The research group discovered that MuSK protein, which is originally anchored to the membrane surface of skeletal muscle, is cleaved from skeletal muscle and released into the bloodstream when neuromuscular synapse dysfunction, which occurs before the onset of muscle atrophy, triggers its release. We are currently investigating effective interventions against sarcopenia using this blood biomarker.

2. Our second research goal is to investigate the causes of chronic inflammation, one of the main causes of frailty, and its early diagnosis and intervention.

1. 1. Mori S, Suzuki S, Konishi T, Kawaguchi N, Kishi M, Kuwabara S, Ishizuchi K, Zhou H, Shibasaki F, Tsumoto H, Omura T, Miura Y, Mori S, Higashihara M, Murayama S and Shigemoto K. Proteolytic etodomain shedding of muscle-specific kinase in myasthenia gravis. Exp Neurol, 2023; 36:114300
2. 2. Hott S, Iimura K, Watanabe N, Suzuki H, Sugie M and Shigemoto K. Sympathetic modulation of hindlimb muscle contractility is altered in aged rats. Sci.Rep, 2023; 13(1):7504.
3. 3. Hotta H, Iimura K, Watanabe N and Shigemoto K. Maintenance of contractile force of the hind limb muscles by the somato-lumbar sympathetic reflexes.　J Phsiol Sci, 2021; 71(1):15.
4. 4. Fukunaga T, Mori S, Omura T, Noda Y, Fujita Y, Ohsawa I, Shigemoto K. Muscle fiber type specific alterations of mitochondrial respiratory function and morphology in aged female mice. BBRC, 2021; 540:116-122.
5. 5. Miyazaki T, Zhao Z, Ichihara Y, Yoshino D, Imamura T, Sawada K, Hayano S, Kamioka H, Mori S, Hirata H, Araki K, Kawauchi K, Shigemoto K, Tanaka S, Bonewald LF, Honda H, Shinohara M, Nagao M, Ogata T, Harada I, Sawada Y. Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-kB activity. Sci Adv, 2019;5: eaau7802.
6. 6. Nishimune H, Badawi Y, Mori S and Shigemoto K. Dual-color STED microscopy reveals a sandwich structure of Bassoon and Piccolo in active zones of adult and aged mice. Sci.Rep, 2016; 6:27935.