Updated on 2023/09/29

写真a

 
NAKAZAWA Yuka
 
Organization
Research Institute of Environmental Medicine Division of Stress Adaptation and Protection Lecturer
Graduate School
Graduate School of Medicine
Title
Lecturer

Degree 1

  1. 博士 (医学) ( 長崎大学 ) 

Research Interests 4

  1. DNA repair, human genetics, nucleotide excision repair

  2. 転写共役修復

  3. ブロックオリゴ

  4. VUS

Research Areas 4

  1. Environmental Science/Agriculture Science / Radiation influence  / DNA修復

  2. Life Science / Molecular biology

  3. Environmental Science/Agriculture Science / Chemical substance influence on environment  / DNA修復

  4. Life Science / Pathological biochemistry

Research History 1

  1. 名古屋大学 環境医学研究所 生体適応・防御研究部門 発生・遺伝分野 講師

    2021.5

 

Papers 34

  1. Deep intronic founder mutations identified in the ERCC4/XPF gene are potential therapeutic targets for a high-frequency form of xeroderma pigmentosum. Reviewed International journal

    Chikako Senju*, Yuka Nakazawa*, Taichi Oso*, Mayuko Shimada, Kana Kato, Michiko Matsuse, Mariko Tsujimoto, Taro Masaki, Yasushi Miyazaki, Satoshi Fukushima, Satoshi Tateishi, Atsushi Utani, Hiroyuki Murota, Katsumi Tanaka, Norisato Mitsutake, Shinichi Moriwaki, Chikako Nishigori, Tomoo Ogi

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 120 ( 27 ) page: e2217423120   2023.7

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    Xeroderma pigmentosum (XP) is a genodermatosis defined by cutaneous photosensitivity with an increased risk of skin tumors because of DNA repair deficiency. The worldwide prevalence of XP is ~1 to 4 in million, with higher incidence in some countries and regions including Japan (1 in 22,000) and North Africa due to founder mutations and a high degree of consanguinity. Among XP, the complementation group F (XP-F), is a rare form (1% of worldwide XP); however, this is underdiagnosed, because the ERCC4/XPF gene is essential for fetal development and most of previously reported ERCC4/XPF pathogenic variants are hypomorphs causing relatively mild phenotypes. From the largest Japanese XP cohort study, we report 17 XP-F cases bearing two pathogenic variants, both identified in deep intronic regions of the ERCC4/XPF gene. The first variant, located in intron 1, is a Japanese founder mutation, which additionally accounts for ~10% of the entire Japanese XP cases (MAF = 0.00196), causing an aberrant pre-mRNA splicing due to a miss-binding of U1snRNA. The second mutation located in intron eight induces an alternative polyadenylation. Both mutations cause a reduction of the ERCC4/XPF gene expression, resulting in XP clinical manifestations. Most cases developed early-onset skin cancers, indicating that these variants need critical attention. We further demonstrate that antisense oligonucleotides designed for the mutations can restore the XPF protein expression and DNA repair capacity in the patients' cells. Collectively, these pathogenic variants can be potential therapeutic targets for XP.

    DOI: 10.1073/pnas.2217423120

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  2. Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair Reviewed International coauthorship

    Yuka Nakazawa, Yuichiro Hara, Yasuyoshi Oka, Okiru Komine, Diana van den Heuvel, Chaowan Guo, Yasukazu Daigaku, Mayu Isono, Yuxi He, Mayuko Shimada, Kana Kato, Nan Jia, Satoru Hashimoto, Yuko Kotani, Yuka Miyoshi, Miyako Tanaka, Akira Sobue, Norisato Mitsutake, Takayoshi Suganami, Akio Masuda, Kinji Ohno, Shinichiro Nakada, Tomoji Mashimo, Koji Yamanaka, Martijn S. Luijsterburg, Tomoo Ogi

    Cell   Vol. 180 ( 6 ) page: 1228 - +   2020.3

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    Authorship:Lead author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.cell.2020.02.010

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  3. Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair. Reviewed International coauthorship

    Nakazawa Y, Sasaki K, Mitsutake N, Matsuse M, Shimada M, Nardo T, Takahashi Y, Ohyama K, Ito K, Mishima H, Nomura M, Kinoshita A, Ono S, Takenaka K, Masuyama R, Kudo T, Slor H, Utani A, Tateishi S, Yamashita S, Stefanini M, Lehmann AR, Yoshiura KI, Ogi T§.

    Nature Genetics   Vol. 44   page: 586-592   2012.5

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    DOI: 10.1038/ng.2229.

  4. XRCC4 deficiency in human subjects causes a marked neurological phenotype but no overt immunodeficiency. Reviewed International coauthorship

    Guo C*, Nakazawa Y*, Woodbine L*, Bjorkman A, Shimada M, Fawcett H, Jia N, Ohyama K, Li TS, Nagayama Y, Mitsutake N, Pan-Hammarstrom Q, Gennery AR, Lehmann AR, Jeggo PA, Ogi T§.

    Journal of Allergy and Clinical Immunology   Vol. 136   page: 1007-1017   2015.10

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    DOI: 10.1016/j.jaci.2015.06.007.

  5. A rapid comprehensive assay system for DNA repair activity and cytotoxic effects of DNA damaging reagents by measuring unscheduled DNA synthesis and recovery of RNA synthesis after DNA damage. Reviewed International coauthorship

    Jia N*, Nakazawa Y*, Guo C, Shimada M, Sethi M, Takahashi Y, Ueda H, Nagayama Y, Ogi T§.

    Nature Protocols   Vol. 10   page: 12-24   2015.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nprot.2014.194.

  6. Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia. Reviewed International coauthorship

    Kashiyama K*, Nakazawa Y*, Pilz D*, Guo C*, Shimada M, Sasaki K, Fawcett H, Wing J, Lewin S, Carr L, Li TS, Yoshiura K, Utani A, Hirano A, Yamashita S, Greenblatt D, Nardo T, Stefanini M, McGibbon D, Sarkany R, Fassihi H, Takahashi Y, Nagayama Y, Mitsutake N, Lehmann AR§, Ogi T§.

    American Journal of Human Genetics   Vol. 92   page: 807-819   2013.5

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    DOI: 10.1016/j.ajhg.2013.04.007.

  7. Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.

    Tomita A, Sasanuma H, Owa T, Nakazawa Y, Shimada M, Fukuoka T, Ogi T, Nakada S

    Nature communications   Vol. 14 ( 1 ) page: 5607   2023.9

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    Language:English   Publisher:Nature Communications  

    CRISPR/Cas9-mediated gene editing has great potential utility for treating genetic diseases. However, its therapeutic applications are limited by unintended genomic alterations arising from DNA double-strand breaks and random integration of exogenous DNA. In this study, we propose NICER, a method for correcting heterozygous mutations that employs multiple nicks (MNs) induced by Cas9 nickase and a homologous chromosome as an endogenous repair template. Although a single nick near the mutation site rarely leads to successful gene correction, additional nicks on homologous chromosomes strongly enhance gene correction efficiency via interhomolog homologous recombination (IH-HR). This process partially depends on BRCA1 and BRCA2, suggesting the existence of several distinct pathways for MN-induced IH-HR. According to a genomic analysis, NICER rarely induces unintended genomic alterations. Furthermore, NICER restores the expression of disease-causing genes in cells derived from genetic diseases with compound heterozygous mutations. Overall, NICER provides a precise strategy for gene correction.

    DOI: 10.1038/s41467-023-41048-5

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  8. A case of Cockayne syndrome with unusually mild clinical manifestations

    Tsujimoto Mariko, Nakano Eiji, Nakazawa Yuka, Kanda Fumio, Ueda Takehiro, Ogi Tomoo, Nishigori Chikako

    JOURNAL OF DERMATOLOGY   Vol. 50 ( 4 ) page: 541 - 545   2023.4

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    Language:English   Publisher:Journal of Dermatology  

    We present a mild case of Cockayne syndrome that was referred to us with an extreme sunburn at the age of 3. In early teens, although her cutaneous symptoms alleviated without any medications, she developed tremor and dysarthria. Neurological examination and brain imaging suggested demyelination disorders. The patient's cells indicated a reduced recovery of RNA synthesis, which was partially restored by the introduction of CSB (Cockayne Syndrome B)-cDNA. In addition, her cells indicated a substantially reduced level of CSB protein. Despite the insidious progression of neurological symptoms, she gave birth to a child. Such mild cases of Cockayne syndrome may be misdiagnosed.

    DOI: 10.1111/1346-8138.16679

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  9. Aicardi-Goutières syndrome with SAMHD1 deficiency can be diagnosed by unscheduled DNA synthesis test. International journal

    Chikako Senju, Yuka Nakazawa, Mayuko Shimada, Dai Iwata, Michiko Matsuse, Katsumi Tanaka, Yasushi Miyazaki, Shinichi Moriwaki, Norisato Mitsutake, Tomoo Ogi

    Frontiers in pediatrics   Vol. 10   page: 1048002 - 1048002   2022.11

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    Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterised by progressive encephalopathy, involving microcephaly, intracranial calcification, and cerebrospinal fluid lymphocytosis with increased interferon-α concentrations. The clinical features of AGS overlap with fetal cerebral anomalies caused by congenital infections, such as TORCH (toxoplasmosis, other, rubella, cytomegalovirus, and herpes), or with those of other genetic disorders showing neonatal microcephaly, including Cockayne syndrome (CS) with transcription-coupled DNA repair deficiency, and Seckel syndrome (SS) showing aberrant cell-cycle checkpoint signaling. Therefore, a differential diagnosis to confirm the genetic cause or a proof of infection should be considered. In this report, we describe an individual who showed primordial dwarfism and encephalopathy, and whose initial diagnosis was CS. First, we conducted conventional DNA repair proficiency tests for the patient derived fibroblast cells. Transcription-coupled nucleotide excision repair (TC-NER) activity, which is mostly compromised in CS cases, was slightly reduced in the patient's cells. However, unscheduled DNA synthesis (UDS) was significantly diminished. These cellular traits were inconsistent with the diagnosis of CS. We further performed whole exome sequencing for the case and identified a compound heterozygous loss-of-function variants in the SAMHD1 gene, mutations in which are known to cause AGS. As SAMHD1 encodes deoxyribonucleoside triphosphate triphosphohydrolase, we reasoned that the deoxyribonucleoside triphosphate (dNTP) pool size in the patient's cells was elevated, and the labeling efficiency of UDS-test was hindered due to the reduced concentration of phosphorylated ethynyl deoxyuridine (EdU), a nucleoside analogue used for the assay. In conclusion, UDS assay may be a useful diagnostic tool to distinguish between AGS with SAMHD1 mutations and other related diseases.

    DOI: 10.3389/fped.2022.1048002

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  10. Dealing with transcription-blocking DNA damage: Repair mechanisms, RNA polymerase II processing and human disorders Reviewed International coauthorship

    Jia Nan, Guo Chaowan, Nakazawa Yuka, Heuvel Diana van den, Luijsterburg Martijn S., Ogi Tomoo

    DNA REPAIR   Vol. 106   page: 103192   2021.10

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:DNA Repair  

    Transcription-blocking DNA lesions (TBLs) in genomic DNA are triggered by a wide variety of DNA-damaging agents. Such lesions cause stalling of elongating RNA polymerase II (RNA Pol II) enzymes and fully block transcription when unresolved. The toxic impact of DNA damage on transcription progression is commonly referred to as transcription stress. In response to RNA Pol II stalling, cells activate and employ transcription-coupled repair (TCR) machineries to repair cytotoxic TBLs and resume transcription. Increasing evidence indicates that the modification and processing of stalled RNA Pol II is an integral component of the cellular response to and the repair of TBLs. If TCR pathways fail, the prolonged stalling of RNA Pol II will impede global replication and transcription as well as block the access of other DNA repair pathways that may act upon the TBL. Consequently, such prolonged stalling will trigger profound genome instability and devastating clinical features. In this review, we will discuss the mechanisms by which various types of TBLs are repaired by distinct TCR pathways and how RNA Pol II processing is regulated during these processes. We will also discuss the clinical consequences of transcription stress and genotype-phenotype correlations of related TCR-deficiency disorders.

    DOI: 10.1016/j.dnarep.2021.103192

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  11. Dealing with transcription-blocking DNA damage: Repair mechanisms, RNA polymerase II processing and human disorders.

    Nan Jia, Chaowan Guo, Yuka Nakazawa, Diana van, den Heuvel, Martijn S Luijsterburg, Tomoo Ogi

    DNA Repair     2021.10

  12. ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation. Reviewed International coauthorship International journal

    Yana van der Weegen, Klaas de Lint, Diana van den Heuvel, Yuka Nakazawa, Tycho E T Mevissen, Janne J M van Schie, Marta San Martin Alonso, Daphne E C Boer, Román González-Prieto, Ishwarya V Narayanan, Noud H M Klaassen, Annelotte P Wondergem, Khashayar Roohollahi, Josephine C Dorsman, Yuichiro Hara, Alfred C O Vertegaal, Job de Lange, Johannes C Walter, Sylvie M Noordermeer, Mats Ljungman, Tomoo Ogi, Rob M F Wolthuis, Martijn S Luijsterburg

    Nature cell biology   Vol. 23 ( 6 ) page: 595 - 607   2021.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)  

    Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. DNA damage-induced binding of the TCR-specific repair factor CSB to RNA polymerase II (RNAPII) triggers RNAPII ubiquitylation of a single lysine (K1268) by the CRL4CSA ubiquitin ligase. How CRL4CSA is specifically directed towards K1268 is unknown. Here, we identify ELOF1 as the missing link that facilitates RNAPII ubiquitylation, a key signal for the assembly of downstream repair factors. This function requires its constitutive interaction with RNAPII close to K1268, revealing ELOF1 as a specificity factor that binds and positions CRL4CSA for optimal RNAPII ubiquitylation. Drug-genetic interaction screening also revealed a CSB-independent pathway in which ELOF1 prevents R-loops in active genes and protects cells against DNA replication stress. Our study offers key insights into the molecular mechanisms of TCR and provides a genetic framework of the interplay between transcriptional stress responses and DNA replication.

    DOI: 10.1038/s41556-021-00688-9

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  13. Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome Reviewed

    Oka Yasuyoshi, Hamada Motoharu*, Nakazawa Yuka*, Muramatsu Hideki*, Okuno Yusuke*, Higasa Koichiro*, Shimada Mayuko, Takeshima Honoka, Hanada Katsuhiro, Hirano Taichi, Kawakita Toshiro, Sakaguchi Hirotoshi, Ichimura Takuya, Ozono Shuichi, Yuge Kotaro, Watanabe Yoriko, Kotani Yuko, Yamane Mutsumi, Kasugai Yumiko, Tanaka Miyako, Suganami Takayoshi, Nakada Shinichiro, Mitsutake Norisato, Hara Yuichiro, Kato Kohji, Mizuno Seiji, Miyake Noriko, Kawai Yosuke, Tokunaga Katsushi, Nagasaki Masao, Kito Seiji, Isoyama Keiichi, Onodera Masafumi, Kaneko Hideo, Matsumoto Naomichi, Matsuda Fumihiko, Matsuo Keitaro, Takahashi Yoshiyuki, Mashimo Tomoji, Kojima Seiji, Ogi Tomoo

    SCIENCE ADVANCES   Vol. 6 ( 51 )   2020.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Science Advances  

    DOI: 10.1126/sciadv.abd7197

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  14. Topoisomerase I -driven repair of UV -induced damage in NER-deficient cells Reviewed

    Saha Liton Kumar, Wakasugi Mitsuo, Akter Salma, Prasad Rajendra, Wilson Samuel H., Shimizu Naoto, Sasanuma Hiroyuki, Huang Shar-yin Naomi, Agama Keli, Pommier Yves, Matsunaga Tsukasa, Hirota Kouji, Iwai Shigenori, Nakazawa Yuka, Ogi Tomoo, Takeda Shunichi

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   Vol. 117 ( 25 ) page: 14412-14420   2020.6

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    DOI: 10.1073/pnas.1920165117

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  15. Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex. Reviewed

    Kato K, Okuno Y, Vasilev FF, Otomo T, Oishi H, Muramatsu H, Kawano Y, Oka Y, Nakazawa Y, Ogi T, Takahashi Y, Saitoh S.

    Journal of Medical genetics   Vol. 117 ( 25 ) page: 14412 - 14420   2020.4

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    DOI: 10.1136/jmedgenet-2019-106213

  16. Hailey-Hailey disease with oesophageal involvement due to a previously unreported ATP2C1 mutation.

    Kono M, Kodera M, Inasaka Y, Hasegawa I, Muro Y, Nakazawa Y, Ogi T, Akiyama M

    European journal of dermatology : EJD     2019.8

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    DOI: 10.1684/ejd.2019.3507

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  17. JAK/STAT3 and NF-κB Signaling Pathways Regulate Cancer Stem-Cell Properties in Anaplastic Thyroid Cancer Cells. Reviewed

      Vol. 29 ( 5 ) page: 674-682   2019.5

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    DOI: 10.1089/thy.2018.0212

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  18. A Japanese Case of Galli-Galli Disease due to a Previously Unreported POGLUT1 Mutation. Reviewed

    Kono M, Sawada M, Nakazawa Y, Ogi T, Muro Y, Akiyama M

    Acta dermato-venereologica   Vol. 99 ( 4 ) page: 458 - 459   2019.1

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    DOI: 10.2340/00015555-3119

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  19. Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome Reviewed International coauthorship

    Calmels Nadege, Botta Elena, Jia Nan, Fawcett Heather, Nardo Tiziana, Nakazawa Yuka, Lanzafame Manuela, Moriwaki Shinichi, Sugita Katsuo, Kubota Masaya, Obringer Cathy, Spitz Marie-Aude, Stefanini Miria, Laugel Vincent, Orioli Donata, Ogi Tomoo, Lehmann Alan Robert

    JOURNAL OF MEDICAL GENETICS   Vol. 55 ( 5 ) page: 329-343   2018.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1136/jmedgenet-2017-104877

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  20. Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations

    Doi Hiroshi, Koyano Shigeru, Miyatake Satoko, Nakajima Shinji, Nakazawa Yuka, Kunii Misako, Tomita-Katsumoto Atsuko, Oda Kayoko, Yamaguchi Yukie, Fukai Ryoko, Ikeda Shingo, Kato Rumiko, Ogata Katsuhisa, Kubota Shun, Hayashi Noriko, Takahashi Keita, Tada Mikiko, Tanaka Kenichi, Nakashima Mitsuko, Tsurusaki Yoshinori, Miyake Noriko, Saitsu Hirotomo, Ogi Tomoo, Aihara Michiko, Takeuchi Hideyuki, Matsumoto Naomichi, Tanaka Fumiaki

    JOURNAL OF HUMAN GENETICS   Vol. 63 ( 4 ) page: 417-423   2018.4

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    DOI: 10.1038/s10038-017-0408-5

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  21. An adolescent case of xeroderma pigmentosum variant confirmed by the onset of sun exposure-related skin cancer during Crohn's disease treatment

    Terada Aoi, Aoshima Masahiro, Tanizaki Hideaki, Nakazawa Yuka, Ogi Tomoo, Tokura Yoshiki, Moriwaki Shinichi

    JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY   Vol. 1 ( 1 ) page: 23-26   2018.4

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    DOI: 10.1002/cia2.12011

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  22. Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites Reviewed International coauthorship

    Yasuda Takeshi, Kagawa Wataru, Ogi Tomoo, Kato Takamitsu A., Suzuki Takehiro, Dohmae Naoshi, Takizawa Kazuya, Nakazawa Yuka, Genet Matthew D., Saotome Mika, Hama Michio, Konishi Teruaki, Nakajima Nakako Izumi, Hazawa Masaharu, Tomita Masanori, Koike Manabu, Noshiro Katsuko, Tomiyama Kenichi, Obara Chizuka, Gotoh Takaya, Ui Ayako, Fujimori Akira, Nakayama Fumiaki, Hanaoka Fumio, Sugasawa Kaoru, Okayasu Ryuichi, Jeggo Penny A., Tajima Katsushi

    PLOS GENETICS   Vol. 14 ( 3 ) page: e1007277   2018.3

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    DOI: 10.1371/journal.pgen.1007277

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  23. Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways Reviewed

    Okuda Masahiko, Nakazawa Yuka, Guo Chaowan, Ogi Tomoo, Nishimura Yoshifumi

    NUCLEIC ACIDS RESEARCH   Vol. 45 ( 22 ) page: 13043-13055   2017.12

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    DOI: 10.1093/nar/gkx970

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  24. ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair Reviewed

    Tsuda Masataka, Cho Kosai, Ooka Masato, Shimizu Naoto, Watanabe Reiko, Yasui Akira, Nakazawa Yuka, Ogi Tomoo, Harada Hiroshi, Agama Keli, Nakamura Jun, Asada Ryuta, Fujiike Haruna, Sakuma Tetsushi, Yamamoto Takashi, Murai Junko, Hiraoka Masahiro, Koike Kaoru, Pommier Yves, Takeda Shunichi, Hirota Kouji

    PLOS ONE   Vol. 12 ( 11 ) page: e0188320   2017.11

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    DOI: 10.1371/journal.pone.0188320

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  25. Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells

    Doi Ryoichiro, Tsuchiya Tomoshi, Mitsutake Norisato, Nishimura Satoshi, Matsuu-Matsuyama Mutsumi, Nakazawa Yuka, Ogi Tomoo, Akita Sadanori, Yukawa Hiroshi, Baba Yoshinobu, Yamasaki Naoya, Matsumoto Keitaro, Miyazaki Takuro, Kamohara Ryotaro, Hatachi Go, Sengyoku Hideyori, Watanabe Hironosuke, Obata Tomohiro, Niklason Laura E., Nagayasu Takeshi

    SCIENTIFIC REPORTS   Vol. 7 ( 1 ) page: 8447   2017.8

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    DOI: 10.1038/s41598-017-09115-2

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  26. An XPA gene splicing mutation resulting in trace protein expression in an elderly patient with xeroderma pigmentosum group A without neurological abnormalities. Reviewed

    Takahashi Y, Endo Y, Kusaka-Kikushima A, Nakamaura S, Nakazawa Y, Ogi T, Uryu M, Tsuji G, Furue M, Moriwaki S.

    Br J Dermatol   Vol. 177 ( 1 ) page: 253-257   2017.5

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    DOI: 10.1111/bjd.15051

  27. PCNA ubiquitylation ensures timely completion of unperturbed DNA replication in fission yeast. Reviewed International coauthorship

    Daigaku Y, Etheridge TJ, Nakazawa Y, Nakayama M, Watson AT, Miyabe I, Ogi T, Osborne MA, Carr AM.

    PLoS Genetics   Vol. 13 ( 5 ) page: e1006789   2017.5

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    DOI: 10.1371/journal.pgen.1006789.

  28. A ten-year follow up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole genome sequencing. Reviewed

    Ono R, Masaki T, Mayca Pozo F, Nakazawa Y, Swagemakers SM, Nakano E, Sakai W, Takeuchi S, Kanda F, Ogi T, van der Spek PJ, Sugasawa K, Nishigori C§.

    Photodermatology Photoimmunology & Photomedicine   Vol. 32   page: 174-180   2016.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/phpp.12240.

  29. Novel compound heterozygous DNA ligase IV mutations in an adolescent with a slowly- progressing radiosensitive-severe combined immunodeficiency. Reviewed

    Tamura S, Higuchi K, Tamaki M, Inoue C, Awazawa R, Mitsuki N, Nakazawa Y, Mishima H, Takahashi K, Kondo O, Imai K, Morio T, Ohara O, Ogi T, Furukawa F, Inoue M, Yoshiura K, Kanazawa N§.

    Journal of Clinical Immunology   Vol. 160   page: 255-260   2015.10

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    DOI: 10.1016/j.clim.2015.07.004.

  30. Hypomorphic PCNA mutation underlies a human DNA repair disorder. Reviewed International coauthorship

    Baple EL, Chambers H, Cross HE, Fawcett H, Nakazawa Y, Chioza BA, Harlalka GV, Mansour S, Sreekantan-Nair A, Patton MA, Muggenthaler M, Rich P, Wagner K, Coblentz R, Stein CK, Last JI, Taylor AM, Jackson AP, Ogi T, Lehmann AR, Green CM§, Crosby AH§.

    Journal of Clinical Investigation   Vol. 124   page: 3137-3146   2014.7

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    DOI: 10.1172/JCI74593.

  31. Identification of the First ATRIP-Deficient Patient and Novel Mutations in ATR Define a Clinical Spectrum for ATR-ATRIP Seckel Syndrome. Reviewed International coauthorship

    Ogi T§*, Walker S*, Stiff T, Hobson, E, Limsirichaikul S, Carpenter G, Prescott K, Suri M, Byrd PJ, Matsuse M, Mitsutake N, Nakazawa Y, Vasudevan P, Barrow M, Stewart GS, Taylor AMR§, O'Driscoll M§, Jeggo PA§.

    PLoS Genetics   Vol. 8   page: e1002945   2012.11

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    DOI: 10.1371/journal.pgen.1002945.

  32. Two unrelated patients with MRE11A mutations and Nijmegen breakage syndrome-like severe microcephaly. Reviewed

    Matsumoto Y, Miyamoto T, Sakamoto H, Izumi H, Nakazawa Y, Ogi T, Tahara H, Oku S, Hiramoto A, Shiiki T, Fujisawa Y, Ohashi H, Sakemi Y, Matsuura S§.

    DNA Repair   Vol. 10   page: 314-321   2011.3

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    DOI: 10.1016/j.dnarep.2010.12.002.

  33. A semi-automated non-radioactive system for measuring recovery of RNA synthesis and unscheduled DNA synthesis using ethynyluracil derivatives. Reviewed International coauthorship

    Nakazawa Y, Yamashita S, Lehmann AR, Ogi T§.

    DNA Repair   Vol. 9   page: 506-516   2010.5

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    DOI: 10.1016/j.dnarep.2010.01.015.

  34. Three DNA polymerases, recruited by different mechanisms, carry out NER repair synthesis in human cells. Reviewed International coauthorship

    Ogi T§, Limsirichaikul S*, Overmeer R*, Volker M*, Takenaka K*, Cloney R*, Nakazawa Y*, Niimi A, Miki Y, Jaspers N, Mullenders L*, Yamashita S*, Fousteri M*, Lehmann AR§.

    Molecular Cell   Vol. 37   page: 714-727   2010.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.molcel.2010.02.009.

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Books 2

  1. Molecular cloning and characterisation of UVSSA, the responsible gene for UV-sensitive syndrome.

    Ogi T§, Nakazawa Y, Sasaki K, Guo C, Yoshiura K, Utani A, Nagayama Y.( Role: Joint author)

    Seikagaku  2013 

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    Language:English

  2. 「紫外線高感受性症候群.」, 別冊日本臨床 新領域別症候群シリーズ No.19 先天代謝異常症候群(第2版)(上)

    荻朋男, 中沢由華, 吉浦孝一郎, 宇谷厚志, 永山雄二.( Role: Joint author)

    日本臨床社  2012 

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    Language:Japanese

MISC 1

  1. 長崎大学病院皮膚科・アレルギー科を受診した色素性乾皮症患者の解析と考察

    鍬塚 大, 岩永 聰, 宇谷 厚志, 室田 浩之, 富村 沙織, 郡家 佑美, 中沢 由華, 荻 朋男

    西日本皮膚科   Vol. 84 ( 6 ) page: 574 - 574   2022.12

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    Language:Japanese   Publisher:日本皮膚科学会-西部支部  

Presentations 17

  1. 転写共役修復機構の分子メカニズムとその破綻による生体影響の解明

    中沢由華, 岡泰由, 森永浩伸, 何予希, 荻朋男

    第45回分子生物学会年会  2022.12.2 

  2. Coordinated ubiquitination of RPB1-K1268 and UVSSA-K414 promotes transcription-coupled nucleotide excision repair

    Yuka Nakazawa

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    Event date: 2021.9

    Presentation type:Symposium, workshop panel (nominated)  

  3. 転写と共役したDNA修復機構にはRNAPIIのユビキチン化修飾が必須である

    中沢由華

    第 10 回名古屋大学医学系研究科・生理学研究所合同シンポジウム 

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    Event date: 2020.9

    Presentation type:Oral presentation (general)  

  4. Alterations in the RNA polymerase IIo ubiquitination cause TC-NER defect and Cockayne syndrome-like premature aging phenotype in mice

    Yuka Nakazawa, Yuichiro Hara, Yasuyoshi Oka, Okiru Komine, Diana van den Heuvel, Chaowan Guo, Yasukazu Daigaku, Mayu Isono, Yuxi He, Mayuko Shimada, Kana Katoh, Nan Jia, Satoru Hashimoto, Yuko Kotani, Yuka Miyoshi, Miyako Tanaka, Akira Sobue, Norisato Mitsutake, Takayoshi Suganami, Akio Masuda, Kinji Ohno, Shinichiro Nakada, Tomoji Mashimo, Koji Yamanaka, Martijn S. Luijsterburg, Tomoo Ogi

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    Event date: 2019.12

    Presentation type:Poster presentation  

  5. Alterations in RNA polymerase IIo ubiquitination cause Cockayne syndrome-like premature aging phenotype in mice due to TC-NER defect. International conference

    Yuka Nakazawa

    International Symposium on XP and other Nucleotide Excision Repair Didsorders 

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    Event date: 2019.3

    Language:English   Presentation type:Poster presentation  

    Country:United Kingdom  

  6. ゲノム不安定性を示す遺伝性疾患の分子病態.

    中沢由華

    第3回名大医薬系3部局交流シンポジウム〜岐阜薬科大学・岐阜大学G-CHAIN・ラクオリア創薬合同シンポジウム〜 

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    Event date: 2018.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋市   Country:Japan  

  7. ゲノム不安定性を示す遺伝性疾患群の疾患責任遺伝子変異の探索.

    中沢由華、千住千佳子、岡泰由、嶋田繭子、宮崎仁美、郭朝万、賈楠、荻朋男.

    第40回日本分子生物学会年会 

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    Event date: 2017.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:神戸   Country:Japan  

  8. ゲノム不安定性を示す遺伝性疾患群の病態解析と新規疾患責任遺伝子変異探索.

    中沢由華, 岡泰由, 郭朝万, 賈楠, 唐田清伸, 嶋田繭子, 宮﨑仁美, 千住千佳子, 荻朋男.

    第39回日本分子生物学会年会 

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    Event date: 2016.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:横浜   Country:Japan  

  9. Screening of microcephaly cases to identify pathogenic mutations in DNA repair genes. International conference

    Nakazawa Y, Oka Y, Karata K, Guo C, Lehmann AR, Ogi T.

    The 10th 3R Symposium 

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    Event date: 2016.11

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  10. A Screening of Cockayne syndrome like patients identified a new class of disease associated with mutations in the XRCC4 gene. International conference

    Nakazawa Y, Guo C, Woodbine L, Bjorkman A, Shimada M, Pan-Hammarstrom Q, Gennery AR, Lehmann AR, Jeggo PA, Ogi T.

    10th Quinquennial Conference on Responses to DNA damage: from molecule to disease, 

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    Event date: 2016.4

    Language:English   Presentation type:Poster presentation  

    Venue:Egmond aan Zee, The Netherlands   Country:Netherlands  

  11. ゲノム不安定性を示す難治性遺伝性疾患群の症例収集とゲノム・分子機能解析による病態解明研究

    中沢由華、荻朋男、唐田清伸、郭朝万、岡泰由、 賈楠、嶋田繭子、宮崎仁美、千住千佳子

    第38回日本分子生物学会年会 

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    Event date: 2015.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:神戸   Country:Japan  

  12. XRCC4 deficiency in human subjects causes a marked neurological phenotype but no overt immunodeficiency.

    Nakazawa Y, Ogi T, Guo C, Shimada M, Jia N.

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    Event date: 2015.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  13. ゲノム不安定性を示す難治性遺伝性疾患群の症例収集とゲノム・分子機能解析による病態解明研究

    中沢由華、荻朋男、郭朝万、唐田清伸、岡泰由、賈楠、嶋田繭子、宮崎仁美、千住千佳子

    DNA複製・組換え・修復ワークショップ 

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    Event date: 2015.10

    Language:Japanese   Presentation type:Poster presentation  

    Venue:焼津   Country:Japan  

  14. ERCC1/XPF deficiency causes three NER-deficient disorders: a patient with various symptoms of xeroderma pigmentosum, Cockayne syndrome, and Fanconi anemia. International conference

    Nakazawa Y

    The 9th 3R Symposium 

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    Event date: 2014.11

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  15. Characterization of new pathogenic mutations associated with radiation sensitivity and developmental abnormalities.

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    Event date: 2014.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  16. Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia. International conference

    Nakazawa Y

    11th International Conference on Environmental Mutagens 

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    Event date: 2013.11

    Language:English   Presentation type:Poster presentation  

    Venue:Brazil   Country:Brazil  

  17. RNA polymerase processing in nucleotide-excision-repair-deficient genetic disorders.

    Nakazawa Y

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    Event date: 2012.12

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

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Research Project for Joint Research, Competitive Funding, etc. 3

  1. ゲノム不安定性疾患に対するスプライシング異常を引き起こすVUSの人工核酸を用いた網羅的検証と創薬ターゲットの導出

    Grant number:20ak0101146  2020.12 - 2023.3

    創薬基盤推進研究事業 

    中沢由華

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    Authorship:Principal investigator  Grant type:Competitive

  2. ゲノム不安定性疾患群を中心とした超希少難治性疾患の原因究明・病態理解とマルチオミクス情報を活用した創薬基盤の構築・運営

    2023.9 - 2026.3

    難治性疾患実用化研究事業 

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    Authorship:Coinvestigator(s) 

  3. ゲノム不安定性疾患群を中心とした希少難治性疾患の次世代マルチオミクス解析拠点構築

    2020.4 - 2023.3

    難治性疾患実用化研究事業 

    荻朋男

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    Authorship:Coinvestigator(s)  Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 6

  1. 転写共役DNA修復の分子機構と老化関連疾患の分子病態解明

    2023.4 - 2030.3

    国立研究開発法人 科学技術振興機構 (JST)  創発的研究支援事業 

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    Authorship:Principal investigator 

  2. ゲノム不安定性疾患の新規疾患原因遺伝子変異同定法の確立と探索

    Grant number:21K19844  2021.7 - 2023.3

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    中沢 由華

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    Authorship:Principal investigator 

    Grant amount:\6370000 ( Direct Cost: \4900000 、 Indirect Cost:\1470000 )

    次世代ゲノム解析技術が普及し、各種疾患の発症原因となっている遺伝子変異同定が急速に進む一方で、意義が明らかでない変異 (Variants of Uncertain Significance: VUSs)のデータも大量に蓄積されてきている。本研究では、ゲノム不安定性を示す遺伝性疾患を対象に、マルチオミクス的アプローチによりVUSの病原性を評価し疾患原因変異を同定する新たな手法を確立するとともに、疾患治療薬候補の探索にも取り組む。
    次世代ゲノム解析技術が普及してきたことにより、各種疾患の発症原因となっている遺伝子変異の同定が急速に進んできた。しかし、同定される変異の多くは、疾患原因である事の確証が得られやすい、エキソン領域あるいはエキソンとイントロンの境界領域に生じたものである。一方、病的意義が明らかでない変異 (Variants of Uncertain Significance: VUSs)のデータも大量に蓄積されてきているが、これらVUSの疾患発症原因としての検証あるいは生物学的な意義付けについては、十分には行われていない。本研究ではゲノム不安定性を示す遺伝性疾患群を対象として、マルチオミクス的アプローチによりVUSの病原性について検討・評価し、疾患原因変異を同定する新たな手法の構築に取り組む。ゲノム不安定性疾患群は、DNA損傷応答やDNA修復機構の先天的な異常により発症する様々な遺伝性疾患を包括しており、多種類の希少な疾患も含まれる。一般的に、次世代ゲノム解析で疾患原因変異が同定されるのは、およそ30-40%程度と言われており、残りの60-70%は発症原因が不明なままである。そこで、次世代ゲノム解析のみでは疾患原因が特定できないゲノム不安定性疾患疑い症例について、VUSの病原性評価により新規疾患原因変異の特定を目指す。また、マルチオミクス的アプローチを応用して、疾患治療薬・緩和薬・予防薬の探索にも取り組む。本年度は、ゲノム不安定性疾患疑い症例の収集を実施したほか、次世代ゲノム解析で検出されたVUSに関してマルチオミクス的解析を実施し、病原性の検討と評価を進めた。その結果、いくつかの症例についてVUSの中から新規疾患原因変異を特定することができた。
    本研究計画をもとに、ゲノム不安定性を示す遺伝性疾患が疑われる症例で、次世代ゲノム解析のみでは疾患原因変異の同定が困難であったケースを対象に、ゲノム解析で抽出されたVUSについて、マルチオミクス的アプローチによりその病原性の検討と評価を実施した。その結果、いくつかの症例でVUSの中から新規の疾患原因変異を同定することが可能であり、本法の有効性が確認された。また、本解析方法は疾患治療薬・緩和薬・予防薬探索への応用が可能と考えられ、現在検討を進めているほか、ゲノム不安定性疾患疑い症例の収集も実施した。これらのことから、本研究課題は順調に進展していると考えられる。
    初年度、次世代ゲノム解析のみでは疾患原因変異が同定されなかったゲノム不安定性疾患疑い症例について、検出されたVUSを対象にマルチオミクス的アプローチによりその病原性の検討と評価を行ったところ、疾患原因変異の特定が可能であった。このことから引き続き、本解析方法を用いて、VUSの病原性検証を実施し、新規疾患原因変異の同定を進める。また、より精度の高い解析方法とするため、適宜改良と検証を実施する。さらに、疾患治療薬・緩和薬・予防薬の創出に向けて現在検討を進めている探索方法への応用について、より詳細な調査を実施し候補薬の特定を目指すほか、ゲノム不安定性疾患が疑われる症例の収集も継続して実施する。

  3. 転写共役修復 (TCR)の分子メカニズム解明とTCR欠損ヒト遺伝性疾患の分子病態

    Grant number:21H02399  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    中沢 由華

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    Authorship:Principal investigator 

    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

    転写と共役したDNA修復機構 (transcription coupled repair: TCR)は、転写が活発に行われている領域に生じたDNA損傷を効率良く修復するシステムであり、生体の恒常性維持に重要なメカニズムである。本研究では、DNA損傷箇所で停止したRNA合成酵素がユビキチン化修飾を受けてTCRを開始・制御する分子機構の詳細解明に取り組むとともに、TCRの破綻により発症するヒト疾患の病態を明らかにすることを目指す。

  4. DNA二本鎖切断修復機構に関与する機能未知の小頭症新規責任因子の分子機能解析

    Grant number:17H01877  2017.4 - 2020.3

    科学研究費助成事業  基盤研究(B)

    中沢由華

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    Authorship:Principal investigator 

  5. チェルノブイリ放射線誘発甲状腺がんの遺伝子バンク設立と分子遺伝疫学国際共同研究

    2020 - 2024.3

    科学研究費助成事業 

    光武範吏

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    Authorship:Coinvestigator(s) 

  6. 放射線誘発二重鎖切断損傷修復に関与する新規疾患責任遺伝子の分子機能解析

    Grant number:15H05333  2015.4 - 2017.3

    日本学術振興会  科学研究費助成事業  若手研究(A)

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    Authorship:Principal investigator 

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Industrial property rights 3

  1. 色素性乾皮症F群治療薬

    荻朋男、中沢由華、小泉誠、小路貴生

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    Application no:特願2019-218038  Date applied:2019.12

    Country of applicant:Domestic  

  2. 損傷DNA修復物質のスクリーニング方法

    荻朋男、リムシリチャイクルシリパン、中沢由華、山下俊一

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    Patent/Registration no:特許第5549908号  Date registered:2014.5 

    Country of applicant:Domestic  

  3. 日焼けの原因遺伝子

    荻朋男、中沢由華、吉浦孝一郎、佐々木健介

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    Patent/Registration no:特許第5800180号  Date registered:2015.9 

    Country of applicant:Domestic  

 

Teaching Experience (On-campus) 7

  1. 基礎医科学実習ベーシックトレーニング

    2023

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    ヒト細胞を用いたDNA損傷修復活性の測定

  2. 環境学入門

    2023

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    遺伝子検査とゲノム医学

  3. 基盤医科学実習ベーシックトレーニング

    2022

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    ヒト細胞を用いたDNA損傷修復活性の測定

  4. 自然環境と人間

    2021

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    本授業科目は、生命科学・医学系分野のテーマについて、学際的、総合的に分析,把握する能力を育むとともに、他の学問分野との関連性について理解することが目的である。本講義の前半は、人体を構成する臓器、細胞、ゲノムに焦点を当て「ゲノムと環境」「免疫・代謝と疾患」を、後半は、脳神経系による外環境の認知と適応に関して「脳科学と疾患」をテーマとして取り上げる。医学・生命科学に関するこれらのテーマについて基礎から最新の話題、最先端の研究まで幅広く学ぶ。

  5. 基盤医科学実習ベーシックトレーニング

    2021

     詳細を見る

    ヒト細胞を用いたDNA損傷修復活性の測定

  6. 基盤医科学実習ベーシックトレーニング

    2020

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    ヒト細胞を用いた転写共役DNA修復活性の測定

  7. 自然環境と人間

    2020

     詳細を見る

    本授業科目は、生命科学・医学系分野のテーマについて、学際的、総合的に分析,把握する能力を育むとともに、他の学問分野との関連性について理解することが目的である。本講義の前半は、人体を構成する臓器、細胞、ゲノムに焦点を当て「ゲノムと環境」「免疫・代謝と疾患」を、後半は、脳神経系による外環境の認知と適応に関して「脳科学と疾患」をテーマとして取り上げる。医学・生命科学に関するこれらのテーマについて基礎から最新の話題、最先端の研究まで幅広く学ぶ。

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