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【演者】 Shang Ma先生(Children’s Medical Center Research Institu【演題】Biophysical basis of human disease

第37回システム発生・再生医学分野セミナー(東京工業大学 野々村恵子先生との共同開催) 日時: 令和5年3月24日(金)11:00-12:00 Biomedical research has primarily focused on understanding the role of chemical signaling pathways in regulating cellular functions. However, considerably less is known about mechanotransduction, the conversion of force into biological signals, which can be accomplished by the activation of ion channels and other membrane receptors. PIEZOs, the first vertebrate mechanically activated ion channels, are the long-sought sensor for well-known mechanotransduction phenomena such as touch, breathing and urination. Since PIEZOs are professional ion channels for detecting mechanics in the human body, we have used them as molecular handles to study human diseases that have strong physical basis. My unique approach of selecting phenotypes from human genetics and elucidating the mechanism of action in transgenic model has yielded unexpected and important insights into mechanotransduction processes in human disorders. My findings show that overactive PIEZO1 causes red blood cell dehydration via modulating potassium channel activity. Interestingly, this red cell defect confers resistance to malaria, which seems to be relevant to a large human population. Overactive PIEZO1 in macrophages causes late-onset iron overload through inducing enhancing phagocytosis and red blood cell recycling. Recently, my work has revealed a new role for mechanosensory neurons: excessive mechanosensation within these sensory neurons disrupt musculoskeletal development.





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