ヒトの病気のメカニズムを明らかにすることを研究テーマにしています。 このテーマに対して、

1. ヒト疾患の遺伝子解析による原因遺伝子変異の同定（原因同定）
2. ヒト遺伝子変異に基づいた変異ノックインマウスモデルの解析（病態解明）

という2つのアプローチで取り組んでいます。

原因の同定では、次世代シークエンサーを用いた疾患遺伝子解析を行います。これまでに多くのヒト疾患の原因遺伝子を同定してきた実績があります（下記研究業績を参照）

病態の解明では、CRISPR/Cas9システムを用いた疾患マウスモデル作製および解析に取り組んでいます（業績1）。

主な研究業績 (Google Scholar: https://scholar.google.com/citations?user=1u7hzAkAAAAJ&hl=ja/)

1. Aoto K*, Kato M, Akita T, Nakashima M, Mutoh H, Akasaka N, Tohyama J, Nomura Y, Hoshino K, Ago Y, Tanaka R, Epstein O, Ben-Haim R, Heyman E, Miyazaki T, Belal H, Takabayashi S, Ohba C, Takata A, Mizuguchi T, Miyatake S, Miyake N, Fukuda A, Matsumoto N,* and Saitsu H*. ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H⁺-ATPases is essential for brain development in humans and mice. Nat Commun. 2021

2. Nakashima M, Kato M, Aoto K, Shiina M, Belal H, Mukaida S, Kumada S, Sato A, Zerem A, Lerman-Sagie T, Lev D, Leong HY, Tsurusaki Y, Mizuguchi T, Miyatake S, Miyake N, Ogata K, Saitsu H, Matsumoto N. De Novo Hotspot Variants in CYFIP2 Cause Early-Onset Epileptic Encephalopathy. Ann Neurol. 2018

3. Mutoh H#, Kato M#, Akita T#, Shibata T, Wakamoto H, Ikeda H, Kitaura H, Aoto K, Nakashima M, Wang T, Ohba C, Miyatake S, Miyake N, Kakita A, Miyake K, Fukuda A, Matsumoto N, Saitsu H. Biallelic Variants in CNPY3, Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy. Am J Hum Genet. 2018

4. Nakashima M, Saitsu H, Takei N, Tohyama J, Kato M, Kitaura H, Shiina M, Shirozu H, Masuda H, Watanabe K, Ohba C, Tsurusaki Y, Miyake N, Zheng Y, Sato T, Takebayashi H, Ogata K, Kameyama S, Kakita A, Matsumoto N. Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb. Ann Neurol. 2015

5. Nakamura K, Kodera H, Akita T, Shiina M, Kato M, Hoshino H, Terashima H, Osaka H, Nakamura S, Tohyama J, Kumada T, Furukawa T, Iwata S, Shiihara T, Kubota M, Miyatake S, Koshimizu E, Nishiyama K, Nakashima M, Tsurusaki Y, Miyake N, Hayasaka K, Ogata K, Fukuda A, Matsumoto N, Saitsu H. De Novo mutations in GNAO1, encoding a Gαo subunit of heterotrimeric G proteins, cause epileptic encephalopathy. Am J Hum Genet. 2013

6. Saitsu H, Nishimura T, Muramatsu K, Kodera H, Kumada S, Sugai K, Kasai-Yoshida E, Sawaura N, Nishida H, Hoshino A, Ryujin F, Yoshioka S, Nishiyama K, Kondo Y, Tsurusaki Y, Nakashima M, Miyake N, Arakawa H, Kato M, Mizushima N, Matsumoto N. De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood. Nat Genet. 2013

7. Yoneda Y, Haginoya K, Kato M, Osaka H, Yokochi K, Arai H, Kakita A, Yamamoto T, Otsuki Y, Shimizu S, Wada T, Koyama N, Mino Y, Kondo N, Takahashi S, Hirabayashi S, Takanashi J, Okumura A, Kumagai T, Hirai H, Nabetani M, Saitoh S, Hattori A, Yamasaki M, Kumakura A, Sugo Y, Nishiyama K, Miyatake S, Tsurusaki Y, Doi H, Miyake N, Matsumoto N, Saitsu H. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Ann Neurol. 2013

8. Yoneda Y, Haginoya K, Arai H, Yamaoka S, Tsurusaki Y, Doi H, Miyake N, Yokochi K, Osaka H, Kato M, Matsumoto N, and Saitsu H. De novo and inherited mutations in COL4A2, encoding the type IV collagen α2 chain cause porencephaly. Am J Hum Genet. 2012

9. Saitsu H, Osaka H, Sasaki M, Takanashi J, Hamada K, Yamashita A, Shibayama H, Shiina M, Kondo Y, Nishiyama K, Tsurusaki Y, Miyake N, Doi H, Ogata K, Inoue K, Matsumoto N. Mutations in POLR3A and POLR3B Encoding RNA Polymerase III Subunits Cause an Autosomal-Recessive Hypomyelinating Leukoencephalopathy. Am J Hum Genet. 2011

10. Okada I, Hamanoue H, Terada K, Tohma T, Megarbane A, Chouery E, Abou-Ghoch J, Jalkh N, Cogulu O, Ozkinay F, Horie K, Takeda J, Furuichi T, Ikegawa S, Nishiyama K, Miyatake S, Nishimura A, Mizuguchi T, Niikawa N, Hirahara F, Kaname T, Yoshiura K, Tsurusaki Y, Doi H, Miyake N, Furukawa T, Matsumoto N, Saitsu H. SMOC1 is essential for ocular and limb development in humans and mice. Am J Hum Genet. 2011

11. Saitsu H, Tohyama J, Kumada T, Egawa K, Hamada K, Okada I, Mizuguchi T, Osaka H, Miyata R, Furukawa T, Haginoya K, Hoshino H, Goto T, Hachiya Y, Yamagata T, Saitoh S, Nagai T, Nishiyama K, Nishimura A, Miyake N, Komada M, Hayashi K, Hirai S, Ogata K, Kato M, Fukuda A, Matsumoto N. Dominant negative mutations in α-II spectrin cause West syndrome with severe cerebral hypomyelination, spastic quadriplegia, and developmental delay. Am J Hum Genet. 2010

12. Saitsu H, Kato M, Mizuguchi T, Hamada K, Osaka H, Tohyama J, Uruno K, Kumada S, Nishiyama K, Nishimura A, Okada I, Yoshimura Y, Hirai S, Kumada T, Hayasaka K, Fukuda A, Ogata K, Matsumoto N. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy. Nat Genet 40: 782-788, 2008.