チャイ, ムーチー (チャイ ムーチー)

Chai, Muh chyi

写真a

所属(所属キャンパス)

研究所・センター等 グローバルリサーチインスティテュート (三田)

職名

特任助教(有期)

 

論文 【 表示 / 非表示

  • T-type Calcium Channels Determine the Vulnerability of Dopaminergic Neurons to Mitochondrial Stress in Familial Parkinson Disease

    Tabata Y., Imaizumi Y., Sugawara M., Andoh-Noda T., Banno S., Chai M., Sone T., Yamazaki K., Ito M., Tsukahara K., Saya H., Hattori N., Kohyama J., Okano H.

    Stem Cell Reports (Stem Cell Reports)  11 ( 5 ) 1171 - 1184 2018年11月

    ISSN  22136711

     概要を見る

    © 2018 The Author(s) Parkinson disease (PD) is a progressive neurological disease caused by selective degeneration of dopaminergic (DA) neurons in the substantia nigra. Although most cases of PD are sporadic cases, familial PD provides a versatile research model for basic mechanistic insights into the pathogenesis of PD. In this study, we generated DA neurons from PARK2 patient-specific, isogenic PARK2 null and PARK6 patient-specific induced pluripotent stem cells and found that these neurons exhibited more apoptosis and greater susceptibility to rotenone-induced mitochondrial stress. From phenotypic screening with an FDA-approved drug library, one voltage-gated calcium channel antagonist, benidipine, was found to suppress rotenone-induced apoptosis. Furthermore, we demonstrated the dysregulation of calcium homeostasis and increased susceptibility to rotenone-induced stress in PD, which is prevented by T-type calcium channel knockdown or antagonists. These findings suggest that calcium homeostasis in DA neurons might be a useful target for developing new drugs for PD patients. Our study demonstrate the dysregulation of calcium homeostasis and increased susceptibility to rotenone-induced stress in PD patient-derived DA neurons, which are further prevented by T-type calcium channel antagonists. These findings suggest that calcium homeostasis in DA neurons would be a useful target for developing new drugs for PD patients.

  • Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors

    Chai M., Sanosaka T., Okuno H., Zhou Z., Koya I., Banno S., Andoh-Noda T., Tabata Y., Shimamura R., Hayashi T., Ebisawa M., Sasagawa Y., Nikaido I., Okano H., Kohyama J.

    Genes and Development (Genes and Development)  32 ( 2 ) 165 - 180 2018年01月

    ISSN  08909369

     概要を見る

    © 2018 Chai et al. Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function of chromodomain helicase DNA-binding 7 (CHD7) in NE–neural crest bifurcation, thus revealing an etiological link between the central nervous system (CNS) and craniofacial anomalies observed in CHARGE syndrome. We found that CHD7 is required for epigenetic activation of superenhancers and CNS-specific enhancers, which support the maintenance of the NE and CNS lineage identities. Furthermore, we found that BRN2 and SOX21 are downstream effectors of CHD7, which shapes cellular identities by enhancing a CNS-specific cellular program and indirectly repressing non-CNS-specific cellular programs. Based on our results, CHD7, through its interactions with superenhancer elements, acts as a regulatory hub in the orchestration of the spatiotemporal dynamics of transcription factors to regulate NE and CNS lineage identities.

総説・解説等 【 表示 / 非表示

  • Non-Cell-Autonomous Neurotoxicity in Parkinson's Disease Mediated by Astroglial α-Synuclein

    Chai M., Kohyama J.

    Stem Cell Reports (Stem Cell Reports)  12 ( 2 ) 183 - 185 2019年02月

    ISSN  22136711

     概要を見る

    © 2019 The Authors Non-cell-autonomous effects on neuronal cells are considered to be involved in the pathogenesis of neurodegenerative diseases but have yet to be mechanistically proven. In this issue of Stem Cell Reports, di Domenico et al. provide direct evidence that α-synuclein transferred from astrocytes exerts non-cell-autonomous neuronal dysfunction on dopaminergic neurons in Parkinson's disease (PD).