Crosstalk of proteoglycan and filamin and their genetic disorders

• Project/Area Number: 19K07054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Meijo University
• Principal Investigator: Shuji Mizumoto 名城大学, 薬学部, 准教授 (40443973)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: フィラミン / プロテオグリカン / グリコサミノグリカン / 粘液腫性心臓弁膜ジストロフィー / 耳口蓋指症候群 / 前頭骨幹端異形成症 / エーラス・ダンロス症候群 / 偽性捻曲性骨異形成症 / CHST14 / ノックアウトマウス / RNA-seq / コンドロイチン硫酸 / ヘパラン硫酸 / B3GALT6 / ゼブラフィッシュ / B3GAT3 / CSGALNACT1 / CANT1 / 遺伝病

Outline of Research at the Start

コンドロイチン硫酸(CS)、デルマタン硫酸(DS)、ヘパラン硫酸(HS)-プロテオグリカンの生合成に関わる酵素の変異によって、多様な骨・皮膚疾患が引き起こされる。一方、細胞内骨格を構成するフィラミンの異常によっても、同様の骨・皮膚の遺伝性疾患が引き起こされる。しかしながら、細胞内フィラミンと細胞外のCS/DS/HSがどのように関わり、同様の遺伝病を発症するかについてはほとんど研究がなされておらず、不明な点が多い。そこで、本研究では細胞内フィラミンと細胞外CS/DS/HS-プロテオグリカンのクロストークについて明らかにし、それらの遺伝性骨・皮膚疾患の発症機序についても解明することを目的とする。

Outline of Final Research Achievements

To clarify the molecular mechanisms of hereditary skeletal and skin disorders, the crosstalk of Filamin and proteoglycans (PGs) was analyzed. We revealed that the 9-20% increase of levels of glycosaminoglycans (GAGs), which are side chains of PGs, was detected in the patients’ fibroblasts from familial myxomatous polyvalvular dystrophy, Otopalatodigital syndrome, and frontometaphyseal dysplasia with mutations in Filamin A (FLNA). Furthermore, a level of GAGs was elevated in the patients’ fibroblasts from Larsen syndrome with mutation in FLNB. We identified mutations in CANT1, B3GAT3, and DSE, which are involved in the metabolism of PGs, and caused pseudodiastrophic dysplasia and Ehlers-Danlos syndrome musculocontractural type.

Academic Significance and Societal Importance of the Research Achievements

本研究は、様々な遺伝性の骨格・心臓異常を引き起こすフィラミンAやB(FLNA, FLNB)の変異がプロテオグリカンの糖側鎖であるグリコサミノグリカン(GAG)の発現量に影響することを見出した。GAGの発現異常により、同様の遺伝性骨・皮膚・心疾患が引き起こされることを考慮すると、FLNAやFLNBの変異によりGAGの合成異常をきたし、結果として遺伝性疾患が発症するのではないかと考えられた。これらの知見をもとに、心臓や骨疾患における治療法および診断法の開発や治療に貢献できると推察され、本研究成果の学術的意義および社会的意義は非常に大きい。

Research Products

• [Int'l Joint Research] 江南大学(中国)
• [Int'l Joint Research] ゲント大学(ベルギー)
• [Int'l Joint Research] オタゴ大学(ニュージーランド)
• [Int'l Joint Research] University of Otago/University of Auckland(ニュージーランド)
• [Int'l Joint Research] University of New South Wales/University of Melbourne/University of South Australia(オーストラリア)
• [Int'l Joint Research] Medical University of Innsbruck(オーストリア)
• [Int'l Joint Research] Ghent University(ベルギー)
• [Int'l Joint Research] Aalborg University(デンマーク)
• [Int'l Joint Research] University of Otago/University of Auckland(ニュージーランド)
• [Int'l Joint Research] Medical University of Innsbruck(オーストリア)
• [Int'l Joint Research] University of New South Wales/University of Melbourne/University of South Australia(オーストラリア)
• [Int'l Joint Research] Ghent University(ベルギー)
• [Int'l Joint Research] Aalborg University(デンマーク)
• [Journal Article] Memories of Professor Kazuyuki Sugahara (2021)
  • Author(s): Shuji Mizumoto
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 33 Issue: 192 Pages: E49-E50
  • DOI: 10.4052/tigg.2102.7E
  • NAID: 130008002900
  • ISSN: 0915-7352, 1883-2113
  • Year and Date: 2021-03-25
  • Open Access
• [Journal Article] Novel insight into glycosaminoglycan biosynthesis based on gene expression profiles (2021)
  • Author(s): Yi-Fan Huang, Shuji Mizumoto, Morihisa Fujita
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 9 Pages: 709018-709018
  • DOI: 10.3389/fcell.2021.709018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Myopathy associated with dermatan sulfate-deficient decorin and myostatin in musculocontractural Ehlers-Danlos syndrome: a mouse model investigation (2021)
  • Author(s): Yuko Nitahara-Kasahara, Guillermo Posadas-Herrera, Shuji Mizumoto, Aki Nakamura-Takahashi, Yukiko U. Inoue, Takayoshi Inoue, Yoshihiro Nomura, Shin’ichi Takeda, Shuhei Yamada, Tomoki Kosho, Takashi Okada
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 9 Pages: 695021-695021
  • DOI: 10.3389/fcell.2021.695021
  • Peer Reviewed / Open Access
• [Journal Article] A new mouse model of Ehlers-Danlos syndrome generated using CRISPR/Cas9-mediated genomic editing. (2021)
  • Author(s): Yuko Nitahara-Kasahara, Shuji Mizumoto, et al.
  • Journal Title: Disease Models & Mechanisms Volume: 14 Issue: 12
  • DOI: 10.1242/dmm.048963
  • Peer Reviewed / Open Access
• [Journal Article] Congenital Disorders of Deficiency in Glycosaminoglycan Biosynthesis (2021)
  • Author(s): Shuji Mizumoto, Shuhei Yamada
  • Journal Title: Frontiers in Genetics Volume: 12 Pages: 717535-717535
  • DOI: 10.3389/fgene.2021.717535
  • Peer Reviewed / Open Access
• [Journal Article] An Overview of in vivo Functions of Chondroitin Sulfate and Dermatan Sulfate Revealed by Their Deficient Mice (2021)
  • Author(s): Shuji Mizumoto, Shuhei Yamada
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 9 Pages: 764781-764781
  • DOI: 10.3389/fcell.2021.764781
  • Peer Reviewed / Open Access
• [Journal Article] Systematic investigation of the skin in Chst14－/－ mice: a model for skin fragility in musculocontractural Ehlers-Danlos syndrome caused by CHST14 variants (mcEDS-CHST14) (2021)
  • Author(s): Takuya Hirose*, Shuji Mizumoto*, Ayana Hashimoto, Yuki Takahashi, Takahiro Yoshizawa, Yuko Nitahara-Kasahara, Naoki Takahashi, Jun Nakayama, Kazushige Takehana, Takashi Okada, Yoshihiro Nomura, Shuhei Yamada, Tomoki Kosho, Takafumi Watanabe (*equal contribution)
  • Journal Title: Glycobiology Volume: 31 Issue: 2 Pages: 137-150
  • DOI: 10.1093/glycob/cwaa058
  • Peer Reviewed
• [Journal Article] Congenital Disorders Caused by Defects in Catabolism of Glycosaminoglycans (2020)
  • Author(s): Shuhei Yamada, Shuji Mizumoto
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 32 Issue: 188 Pages: E127-E133
  • DOI: 10.4052/tigg.1968.1E
  • NAID: 130007879857
  • ISSN: 0915-7352, 1883-2113
  • Year and Date: 2020-07-25
  • Peer Reviewed / Open Access
• [Journal Article] Congenital Disorders Caused by Defects in Anabolism of Glycosaminoglycans (2020)
  • Author(s): Shuji Mizumoto, Shuhei Yamada
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 32 Issue: 186 Pages: E45-E51
  • DOI: 10.4052/tigg.1759.1E
  • NAID: 130007815517
  • ISSN: 0915-7352, 1883-2113
  • Year and Date: 2020-03-25
  • Peer Reviewed / Open Access
• [Journal Article] Pseudodiastrophic dysplasia expands the known phenotypic spectrum of defects in proteoglycan biosynthesis (2020)
  • Author(s): Alicia B. Byrne, Shuji Mizumoto, Peer Arts, Patrick Yap, Jinghua Feng, Andreas W. Schreiber, Milena Babic, Sarah L. King-Smith, Christopher P. Barnett, Lynette Moore, Kazuyuki Sugahara, Hatice Mutlu-Albayrak, Gen Nishimura, Jan E. Liebelt, Shuhei Yamada, Ravi Savarirayan, Hamish S. Scott
  • Journal Title: Journal of Medical Genetics Volume: 57 Issue: 7 Pages: 454-460
  • DOI: 10.1136/jmedgenet-2019-106700
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Delineation of musculocontractural Ehlers?Danlos Syndrome caused by dermatan sulfate epimerase deficiency (2020)
  • Author(s): Lautrup Charlotte K.、Teik Keng W.、Unzaki Ai、Mizumoto Shuji、Syx Delfien、Sin Heng H.、Nielsen Irene K.、Markholt Sara、Yamada Shuhei、Malfait Fransiska、Matsumoto Naomichi、Miyake Noriko、Kosho Tomoki
  • Journal Title: Molecular Genetics & Genomic Medicine Volume: 8 Issue: 5
  • DOI: 10.1002/mgg3.1197
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] b3galt6 knock-out zebrafish recapitulate β3GalT6-deficiency disorders in human and reveal a trisaccharide proteoglycan linkage region (2020)
  • Author(s): Sarah Delbaere, Adelbert De Clercq, Shuji Mizumoto, Fredrik Noborn, Jan Willem Bek, Lien Alluyn, Charlotte Gistelinck, Delfien Syx, Phil L. Salmon, Paul J. Coucke, Goran Larson, Shuhei Yamada, Andy Willaert, Fransiska Malfait
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 8 Pages: 597857-597857
  • DOI: 10.3389/fcell.2020.597857
  • Open Access / Int'l Joint Research
• [Journal Article] CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age (2020)
  • Author(s): Shuji Mizumoto, Andreas R. Janecke, Azita Sadeghpour, Gundula Povysil, Marie T. McDonald, Sheila Unger, Susanne Greber-Platzer, Kristen L. Deak, Task Force for Neonatal Genomics, Nicholas Katsanis, Andrea Superti-Furga, Erica E. Davis, Shuhei Yamada, Julia Vodopiutz
  • Journal Title: Human Mutation Volume: 41 Issue: 3 Pages: 655-667
  • DOI: 10.1002/humu.23952
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hereditary Skeletal and Skin Disorders Caused by Defects in the Biosynthesis of Chondroitin/Dermatan Sulfate, and Molecular Mechanisms of Pulmonary Metastasis (2019)
  • Author(s): 水本秀二
  • Journal Title: YAKUGAKU ZASSHI Volume: 139 Issue: 12 Pages: 1495-1500
  • DOI: 10.1248/yakushi.19-00140
  • NAID: 130007754062
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2019-12-01
  • Peer Reviewed
• [Journal Article] Functional Analysis of Dermatan Sulfate and Chondroitin Sulfate (2019)
  • Author(s): Shuji Mizumoto
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 31 Issue: 181 Pages: SE98-SE99
  • DOI: 10.4052/tigg.1946.2SE
  • NAID: 130007683650
  • ISSN: 0915-7352, 1883-2113
  • Year and Date: 2019-07-25
• [Journal Article] Hyaluronidase-4 is produced by mast cells and can cleave serglycin chondroitin sulfate chains into lower molecular weight forms (2019)
  • Author(s): Brooke L. Farrugia, Shuji Mizumoto, Megan S. Lord, Robert L. O’Grady, Rhiannon P. Kuchel, Shuhei Yamada, John M. Whitelock
  • Journal Title: Journal of Biological Chemistry Volume: 294 Issue: 30 Pages: 11458-11472
  • DOI: 10.1074/jbc.ra119.008647
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recent Advances in the Pathophysiology of Musculocontractural Ehlers-Danlos Syndrome (2019)
  • Author(s): Tomoki Kosho, Shuji Mizumoto, Takafumi Watanabe, Takahiro Yoshizawa, Noriko Miyake, Shuhei Yamada
  • Journal Title: Genes Volume: 11 Issue: 1 Pages: 43-43
  • DOI: 10.3390/genes11010043
  • NAID: 120006901092
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] グリコサミノグリカンの結合領域四糖の生合成に関わるb3galt6をノックアウトしたゼブラフィッシュの機能解析 (2022)
  • Author(s): 水本秀二, Sarah Delbaere, Adelbert De Clercq, Fredrik Noborn, Jan Willem Bek, Lien Alluyn, Charlotte Gistelinck, Delfien Syx, Phil L. Salmon, Paul J. Coucke, Goran Larson, 山田修平, Andy Willaert, Fransiska Malfait
  • Organizer: 糖鎖科学中部拠点 第17回若手の力 フォーラム、岐阜、1/13
• [Presentation] グリコサミノグリカン生合成に関わるキシロース転移酵素1および2の遺伝性疾患を引き起こす変異が及ぼす酵素活性への影響 (2022)
  • Author(s): 清益慎也、花立妃子、伊藤有美、山田修平、水本秀二
  • Organizer: 糖鎖科学中部拠点 第17回若手の力 フォーラム、岐阜、1/13
• [Presentation] β3ガラクトース転移酵素6 (b3galt6) のゼブラフィッシュ変異体におけるコンドロイチン/デルマタン/ヘパラン硫酸の定量解析 (2022)
  • Author(s): 水本秀二、Sarah Delbaere, Adelbert De Clercq, Fredrik Noborn, Jan Willem Bek, Lien Alluyn, Charlotte Gistelinck, Delfien Syx, Phil L. Salmon, Paul J. Coucke, Goran Larson, 山田修平, Andy Willaert, Fransiska Malfait
  • Organizer: 日本薬学会第142回年会、名古屋、3/28
• [Presentation] グリコサミノグリカン生合成に関わるキシロース転移酵素の遺伝性疾患を引き起こす変異が及ぼす酵素活性への影響 (2022)
  • Author(s): 清益慎也、花立妃子、伊藤有美、山田修平、水本秀二
  • Organizer: 日本薬学会第142回年会、名古屋、3/28
• [Presentation] Pathogenic variants in uridine diphosphate nucleotidase (CANT1) or glucuronyltransferase (B3GAT3) causes a pseudodiastrophic dysplasia (2021)
  • Author(s): Shuji Mizumoto, Alicia B Byrne, Kazuyuki Sugahara, Shuhei Yamada, Hamish S Scott
  • Organizer: 2021 ASBMB Annual Meeting, Athens, 4/29
  • Int'l Joint Research
• [Presentation] グリコサミノグリカンの生合成に関わるb3galt6をノックアウトしたゼブラフィッシュにおけるグリコサミノグリカンの定量解析 (2021)
  • Author(s): Sarah Delbaere，Adelbert De Clercq，水本秀二，Fredrik Noborn, Jan Willem Bek，Lien Alluyn，Charlotte Gistelinck，Delfien Syx，Phil L. Salmon，Paul J. Coucke，Goran Larson，山田修平，Andy Willaert，Fransiska Malfait
  • Organizer: 第85回日本生化学会中部支部例会・シンポジウム、静岡、5/22
• [Presentation] グリコサミノグリカンの結合領域四糖(GlcA-Gal-Gal-Xyl)の生合成に関わるb3galt6を欠損したゼブラフィッシュにおけるグリコサミノグリカンの定量解析 (2021)
  • Author(s): Sarah Delbaere，Adelbert De Clercq，水本秀二，Fredrik Noborn, Jan Willem Bek，Lien Alluyn，Charlotte Gistelinck，Delfien Syx，Phil L. Salmon，Paul J. Coucke，Goran Larson，山田修平，Andy Willaert，Fransiska Malfait
  • Organizer: 第53回日本結合組織学術大会、東京、6/26
• [Presentation] グリコサミノグリカンの生合成に関わるキシロース転移酵素の活性低下が引き起こす遺伝性骨系統疾患 (2021)
  • Author(s): 花立妃子、伊藤有美、山田修平、水本秀二
  • Organizer: 第53回日本結合組織学術大会、東京、6/26
• [Presentation] コンドロイチン/デルマタン/ヘパラン硫酸の結合領域四糖の生合成に関わるb3galt6のゼブラフィッシュ変異体におけるグリコサミノグリカンの定量 (2021)
  • Author(s): 水本秀二、Sarah Delbaere，Adelbert De Clercq，Fredrik Noborn, Jan Willem Bek，Lien Alluyn，Charlotte Gistelinck，Delfien Syx，Phil L. Salmon，Paul J. Coucke，Goran Larson，山田修平，Andy Willaert，Fransiska Malfait
  • Organizer: 第40回日本糖質学会年会、鹿児島、10/28
• [Presentation] グリコサミノグリカンの結合領域四糖の生合成に関わるb3galt6をノックアウトしたゼブラフィッシュにおけるコンドロイチン/デルマタン/ヘパラン硫酸の定量解析 (2021)
  • Author(s): Sarah Delbaere，Adelbert De Clercq，水本秀二、Fredrik Noborn, Jan Willem Bek，Lien Alluyn，Charlotte Gistelinck，Delfien Syx，Phil L. Salmon，Paul J. Coucke，Goan Larson，山田修平，Andy Willaert，Fransiska Malfait
  • Organizer: 第94回日本生化学会大会、横浜、11/3
• [Presentation] グリコサミノグリカンの結合領域四糖の生合成に関わるb3galt6をノックアウトしたゼブラフィッシュにおける骨・皮膚・筋肉の解析 (2021)
  • Author(s): Sarah Delbaere，Adelbert De Clercq，水本秀二、Fredrik Noborn, Jan Willem Bek，Lien Alluyn，Charlotte Gistelinck，Delfien Syx，Phil L. Salmon，Paul J. Coucke，Goran Larson，山田修平，Andy Willaert，Fransiska Malfait
  • Organizer: 第44回日本分子生物学会大会、横浜、12/1
• [Presentation] 脊椎異形成型エーラス・ダンロス症候群のゼブラフィッシュモデル (2021)
  • Author(s): 水本秀二, Sarah Delbaere, Adelbert De Clercq, Fredrik Noborn, Jan Willem Bek, Lien Alluyn, Charlotte Gistelinck, Delfien Syx, Phil L. Salmon, Paul J. Coucke, Goran Larson, 山田修平, Andy Willaert, Fransiska Malfait
  • Organizer: 第2回日本エーラス・ダンロス研究会、栃木、12/11
• [Presentation] ウリジン二リン酸ヌクレオチダーゼあるいはグルクロン酸転移酵素-Iの変異による偽性捻曲性骨異形成症 (2021)
  • Author(s): 水本秀二、Alicia B Byrne、Peer Arts、Patrick Yap、Jinghua Feng、Andreas W Schreiber、Milena Babic、Sarah L King-Smith、Christopher P Barnett、Lynette Moore、菅原一幸、Hatice Mutlu-Albayrak、西村玄、Jan E Liebelt、山田修平、Ravi Savarirayan、Hamish S Scott
  • Organizer: 糖鎖科学中部拠点 第16回若手の力 フォーラム、名古屋、1/22
• [Presentation] カルシウム活性型ヌクレオチダーゼ1(CANT1)とβ3グルクロン酸転移酵素3(B3GAT3)の機能喪失型変異は偽性捻曲性骨異形成症を引き起こす (2021)
  • Author(s): 水本秀二、Alicia B Byrne、Peer Arts、Patrick Yap、Jinghua Feng、Andreas W Schreiber、Milena Babic、Sarah L King-Smith、Christopher P Barnett、Lynette Moore、菅原一幸、Hatice Mutlu-Albayrak、西村玄、Jan E Liebelt、山田修平、Ravi Savarirayan、Hamish S Scott
  • Organizer: 日本薬学会第141回年会、広島、3/27
• [Presentation] グルクロン酸転移酵素-Iおよびウリジン二リン酸ヌクレオチダーゼの変異による偽性捻曲性骨異形成症 (2020)
  • Author(s): 水本秀二, Alicia B Byrne, Peer Arts, Patrick Yap, Jinghua Feng, Andreas W Schreiber, Milena Babic, Sarah L King-Smith, Christopher P Barnett, Lynette Moore, 菅原一幸, Hatice Mutlu-Albayrak, Gen Nishimura, Jan E Liebelt, 山田修平, Ravi Savarirayan, Hamish S Scott
  • Organizer: 第84回日本生化学会中部支部例会・シンポジウム、名古屋、5/24
• [Presentation] Pathogenic variants in glucuronyltransferase-I and calcium-activated nucleotidase-1 cause pseudodiastrophic dysplasia (2020)
  • Author(s): Shuji Mizumoto, Alicia B Byrne, Peer Arts, Patrick Yap, Jinghua Feng, Andreas W Schreiber, Milena Babic, Sarah L King-Smith, Christopher P Barnett, Lynette Moore, Kazuyuki Sugahara, Hatice Mutlu-Albayrak, Gen Nishimura, Jan E Liebelt, Shuhei Yamada, Ravi Savarirayan, Hamish S Scott
  • Organizer: 12th International Symposium on Glycosyltransferases (GlycoT2020), Boston (U.S.A.), 6/21
  • Int'l Joint Research
• [Presentation] 偽性捻曲性骨異形成症はグルクロン酸転移酵素-Iおよびウリジン二リン酸ヌクレオチダーゼの変異によって発症する (2020)
  • Author(s): 水本秀二, Alicia B Byrne, Peer Arts, Patrick Yap, Jinghua Feng, Andreas W Schreiber, Milena Babic, Sarah L King-Smith, Christopher P Barnett, Lynette Moore, 菅原一幸, Hatice Mutlu-Albayrak, Gen Nishimura, Jan E Liebelt, 山田修平, Ravi Savarirayan, Hamish S Scott
  • Organizer: 第93回日本生化学会大会、横浜、9/14
• [Presentation] グリコサミノグリカンの生合成異常による遺伝性の骨・皮膚疾患 (2020)
  • Author(s): 水本秀二
  • Organizer: 第52回日本結合組織学術大会、大府、9/19
  • Invited
• [Presentation] A pseudodiastrophic dysplasia is caused by pathogenic variants in calcium-activated nucleotidase-1 and glucuronyltransferase-I (2020)
  • Author(s): Shuji Mizumoto, Alicia B Byrne, Kazuyuki Sugahara, Shuhei Yamada, Hamish S Scott
  • Organizer: 2020 Annual Meeting of the Society for Glycobiology, U.S.A., 11/9
  • Int'l Joint Research
• [Presentation] UDPヌクレオチダーゼおよびGlcAT-Iの変異は偽性捻曲性骨異形成症を発症する (2020)
  • Author(s): 水本秀二、Alicia B Byrne、Peer Arts、Patrick Yap、Jinghua Feng、Andreas W Schreiber、Milena Babic、Sarah L King-Smith、Christopher P Barnett、Lynette Moore、菅原一幸 、Hatice Mutlu-Albayrak、西村玄、Jan E Liebelt、山田修平、Ravi Savarirayan、Hamish S Scott
  • Organizer: 第39回日本糖質学会年会、東京、11/21
• [Presentation] A skeletal dysplasia with advanced bone age is caused by pathogenic variants in CSGALNACT1 (2020)
  • Author(s): Shuji Mizumoto, Andreas R. Janecke, Azita Sadeghpour, Gundula Povysil, Marie T. McDonald, Sheila Unger, Susanne Greber-Platzer, Nicholas Katsanis, Andrea Superti-Furga, Kazuyuki Sugahara, Erica E. Davis, Shuhei Yamada, Julia Vodopiutz
  • Organizer: 12th Pan Pacific Connective Tissue Societies Symposium 2020, Melbourne (Australia), 11/24
  • Int'l Joint Research
• [Presentation] The role of glycosaminoglycans and their degrading enzymes in inflammatory cell homeostasis (2020)
  • Author(s): Brooke L. Farrugia, Shuji Mizumoto, Megan S. Lord, Shuhei Yamada, and John M. Whitelock
  • Organizer: 12th Pan Pacific Connective Tissue Societies Symposium 2020, Melbourne (Australia), 11/26
  • Int'l Joint Research
• [Presentation] デルマタン硫酸の生合成異常によるエーラス・ダンロス症候群における糖鎖生化学的解析 (2020)
  • Author(s): 水本秀二、山田修平
  • Organizer: 第１回日本エーラス・ダンロス研究会、松本、12/12
• [Presentation] 遺伝性の骨系統疾患を引き起こすキシロース転移酵素のアミノ酸変異による酵素活性への影響 (2020)
  • Author(s): 伊藤有美, 山田修平, 水本秀二
  • Organizer: 日本薬学会第140回年会、京都、3/26
• [Presentation] CSGALNACT1の機能喪失型の変異は骨異形成症を引き起こす (2020)
  • Author(s): 水本秀二, Andreas R. Janecke, Azita Sadeghpour, Gundula Povysil, Marie T. McDonald, Sheila Unger, Susanne Greber-Platzer, Nicholas Katsanis, Andrea Superti-Furga, 菅原一幸, Erica E. Davis, 山田修平, Julia Vodopiutz
  • Organizer: 日本薬学会第140回年会、京都、3/28
• [Presentation] Paternal Isodisomy and Blended Phenotypes: A Pediatric Case with Mosaic Trisomy 8 and a Homozygous CSGALNACT1 Missense Variant (2019)
  • Author(s): Azita Sadeghpour, J. K. Holsclaw, M. T. McDonald, W. B. Gallentine, J. Vodopiutz, A. R. Janecke, S. Yamada, S. Mizumoto, E. E. Davis , N. Katsanis, Task Force for Neonatal Genomics
  • Organizer: American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting, Seattle, U.S.A., 4/6
  • Int'l Joint Research
• [Presentation] Lunatic Fringe (LFNG)の機能喪失変異による脊椎肋骨異骨症 (2019)
  • Author(s): 水本秀二, 武田和樹, 大伴直央, 山田修平, 池川志郎
  • Organizer: 日本生化学会中部支部第82回例会・シンポジウム、名古屋、5/25
• [Presentation] Human mast cells produce the mammalian chondroitinase, hyaluronidase 4 (2019)
  • Author(s): Brooke L. Farrugia, Shuji Mizumoto, Megan S. Lord, Shuhei Yamada, and John M. Whitelock
  • Organizer: 9th EMBRN International Mast Cell and Basophil Meeting / A Marcus Wallenberg symposium, Uppsala, Sweden, 6/17
  • Int'l Joint Research
• [Presentation] Biallelic loss-of-function mutations in CSGALNACT1 cause a skeletal dysplasia with advanced bone age (2019)
  • Author(s): Shuji Mizumoto, Andreas R. Janecke, Azita Sadeghpour, Gundula Povysil, Marie T. McDonald, Sheila Unger, Susanne Greber-Platzer, Task Force for Neonatal Genomics, Nicholas Katsanis, Andrea Superti-Furga, Kazuyuki Sugahara, Erica E. Davis, Shuhei Yamada, Julia Vodopiutz
  • Organizer: 43rd Human Genetics Society of Australasia Annual Scientific Meeting (HGSA2019), Wellington, New Zealand, 8/4
  • Int'l Joint Research
• [Presentation] 脊椎骨端骨幹端異形成症患者のリンパ芽球様細胞株の産生するヘパラン硫酸の解析 (2019)
  • Author(s): 佐藤亨、水本秀二、大橋博文、逆井悦子、Nursel H Elcioglu、三宅紀子、松本直通、池川志郎、山田修平
  • Organizer: 第38回日本糖質学会年会、名古屋、8/20
• [Presentation] コンドロイチン硫酸の生合成を担うCSGALNACT1の変異は骨異形成症を発症する (2019)
  • Author(s): 水本秀二, Andreas R. Janecke, Azita Sadeghpour, Gundula Povysil, Marie T. McDonald, Sheila Unger, Susanne Greber-Platzer, Nicholas Katsanis, Andrea Superti-Furga, 菅原一幸, Erica E. Davis, 山田修平, Julia Vodopiutz
  • Organizer: 第38回日本糖質学会年会、名古屋、8/21
• [Presentation] プロテオグリカン糖側鎖の生合成不全に起因する遺伝性の骨・関節・皮膚・心臓・免疫・神経疾患 (2019)
  • Author(s): 水本秀二
  • Organizer: 第92回日本生化学会大会、横浜、9/18
• [Presentation] Defects in biosynthesis of glycosaminoglycan side chains of proteoglycans cause hereditary bone, skin, heart, and immune disorders (2019)
  • Author(s): Shuji Mizumoto
  • Organizer: Proteoglycans Future Leaders Symposium 2019, Kanazawa, 9/29
  • Int'l Joint Research
• [Presentation] Loss of galactosyltransferase II, encoded by b3galt6, causes musculoskeletal abnormalities in a zebrafish model for spondylodysplastic Ehlers-Danlos syndrome and reveals the presence of a trisaccharide proteoglycan linker region (2019)
  • Author(s): Sarah Delbaere, Shuji Mizumoto, Shuhei Yamada, Fredrik Noborn, Goran Larson, Jan Willem Bek, Phil L. Salmon, Paul Coucke, Andy Willaert, Fransiska Malfait
  • Organizer: Proteoglycans Future Leaders Symposium 2019, Kanazawa, 9/29
  • Int'l Joint Research
• [Presentation] Two types of heparan sulfate clusters differently regulate Wnt distribution and signaling in Xenopus embryos (2019)
  • Author(s): Yusuke Mii, Takayoshi Yamamoto, Ritsuko Takada, Shuji Mizumoto, Makoto Matsuyama, Shuhei Yamada, Masanori Taira, Shinji Takada
  • Organizer: Proteoglycans Future Leaders Symposium 2019, Kanazawa, 9/29
  • Int'l Joint Research
• [Presentation] A skeletal dysplasia with joint laxity and advanced bone age is caused by loss-of-function mutations in CSGALNACT1 (2019)
  • Author(s): Shuji Mizumoto, Andreas R. Janecke, Azita Sadeghpour, Erica E. Davis, Kazuyuki Sugahara, Shuhei Yamada, Julia Vodopiutz
  • Organizer: 11th international Conference on Proteoglyans, Kanazawa, 9/30
  • Int'l Joint Research
• [Presentation] Analysis of heparan sulfate produced by lymphoblastoid cell lines in patients with spondylo-epi-metaphyseal dysplasia (2019)
  • Author(s): Toru Sato, Shuji Mizumoto, Hirofumi Ohashi, Etsuko Sakasai, Nursel H Elcioglu, Noriko Miyake, Naomichi Matsumoto, Shiro Ikegawa, Shuhei Yamada
  • Organizer: 11th international Conference on Proteoglyans, Kanazawa, 9/30
  • Int'l Joint Research
• [Presentation] Human mast cells produce hyaluronidase 1 and 4, that cleaves chondroitin sulfate chains that decorate serglycin (2019)
  • Author(s): Brooke Farrugia, Shuji Mizumoto, Megan Lord, Shuhei Yamada, John Whitelock
  • Organizer: 11th international Conference on Proteoglyans, Kanazawa, 9/30
  • Int'l Joint Research
• [Presentation] Two types of heparan sulfate clusters differently regulate Wnt distribution and signaling in Xenopus embryos (2019)
  • Author(s): Yusuke Mii, Takayoshi Yamamoto, Ritsuko Takada, Shuji Mizumoto, Makoto Matsuyama, Shuhei Yamada, Masanori Taira, Shinji Takada
  • Organizer: 11th international Conference on Proteoglyans, Kanazawa, 10/1
  • Int'l Joint Research
• [Presentation] Loss of galactosyltransferase II, encoded by b3galt6, causes musculoskeletal abnormalities in a zebrafish model for spondylodysplastic Ehlers-Danlos syndrome and reveals the presence of a trisaccharide proteoglycan linker region (2019)
  • Author(s): Sarah Delbaere, Shuji Mizumoto, Shuhei Yamada, Fredrik Noborn, Goran Larson, Jan Willem Bek, Phil L. Salmon, Paul Coucke, Andy Willaert, Fransiska Malfait
  • Organizer: 11th international Conference on Proteoglyans, Kanazawa, 10/2
  • Int'l Joint Research
• [Presentation] Clinical, biochemical, and pathological investigation of a patient with musculocontractural Ehlers-Danlos syndrome caused by a novel pathogenic variant in DSE (2019)
  • Author(s): Mari Minatogawa, Shuji Mizumoto, Takuya Hirose, Tomomi Yamaguchi, Keiko Wakui, Takafumi Watanabe, Shuhei Yamada, Tomoki Kosho
  • Organizer: American Society of Human Genetics (ASHG) 2019, Huston, U.S.A., 10/16
  • Int'l Joint Research
• [Presentation] 新規DSE変異による筋拘縮型エーラスダンロス症候群の日本人第1例における臨床的・糖鎖医学的・病理学的特徴 (2019)
  • Author(s): 湊川真理、水本秀二、広瀬拓哉、山口智美、長江千愛、瀧 正志、涌井敬子、渡邉敬文、山田修平、古庄知己
  • Organizer: 日本人類遺伝学会第64回大会、長崎、11/8
• [Presentation] Chst14遺伝子欠損マウスを用いた筋拘縮型エーラスダンロス症候群(mcEDS)の血管・皮膚症状の病態解析 (2019)
  • Author(s): 吉沢隆浩、嶋田 新、高橋有希、水本秀二、山田修平、古庄知己
  • Organizer: 日本人類遺伝学会第64回大会、長崎、11/8
• [Presentation] Proteoglycan defect-related EDS (2019)
  • Author(s): Shuji Mizumoto
  • Organizer: Scientific Meeting on The Rare Types of Ehlers-Danlos Syndromes, Tokyo, 11/19
  • Int'l Joint Research / Invited
• [Book] コラム11：プロテオグリカンと病気、pp. 268-272、「糖鎖生物学 (生命現象と糖鎖情報)」、編集：北島健、佐藤ちひろ、門松健治、加藤晃一 (2020)
  • Author(s): 水本秀二、山田修平
  • Total Pages: 296
  • Publisher: 名古屋大学出版会
  • ISBN: 9784815809812
• [Remarks] Research Map
  • URL: https://researchmap.jp/read0209443
• [Remarks] ORCID
  • URL: https://orcid.org/0000-0002-4641-1505
• [Remarks] Google Scholar
  • URL: https://scholar.google.co.jp/citations?hl=ja&user=b0ZTepcAAAAJ
• [Remarks] Researchmap
  • URL: http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html
• [Remarks] 名城大学薬学部病態生化学研究室ホームページ
  • URL: http://www-yaku.meijo-u.ac.jp/Research/Laboratory/pathobio/index.html