|
Affiliation |
Faculty of Medicine School of Medicine |
|
Title |
Associate Professor |
|
External Link |
|
UECHI Tamayo
|
|
|
Research Areas 【 display / non-display 】
-
Life Science / Hematology and medical oncology / 先天性貧血
Papers 【 display / non-display 】
-
Matsui H., Ito J., Matsui N., Uechi T., Onodera O., Kakita A.
Nature Communications 12 ( 1 ) 2021.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Communications
Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson’s disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis.
-
Prokaryotic ribosomal RNA stimulates zebrafish embryonic innate immune system Reviewed
Basu A., Yoshihama M., Uechi T., Kenmochi N.
BMC Research Notes 13 ( 1 ) 2020.1
Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Research Notes
Objectives: Cell-culture studies reported that prokaryotic RNA molecules among the various microbe-associated molecular patterns (MAMPs) were uniquely present in live bacteria and were categorized as viability-associated MAMPs. They also reported that specific nucleotide modifications are instrumental in the discrimination between self and nonself RNAs. The aim of this study was to characterize the in vivo immune induction potential of prokaryotic and eukaryotic ribosomal RNAs (rRNAs) using zebrafish embryos as novel whole animal model system. Additionally, we aimed to test the possible role of rRNA modifications in immune recognition. Results: We used three immune markers to evaluate the induction potential of prokaryotic rRNA derived from Escherichia coli and eukaryotic rRNAs from chicken (nonself) and zebrafish (self). Lipopolysaccharide (LPS) of Pseudomonas aeruginosa served as a positive control. E. coli rRNA had an induction potential equivalent to that of LPS. The zebrafish innate immune system could discriminate between self and nonself rRNAs. Between the nonself rRNAs, E. coli rRNA was more immunogenic than chicken rRNA. The in vitro transcript of zebrafish 18S rRNA gene without the nucleotide modifications was not recognized by its own immune system. Our data suggested that prokaryotic rRNA is immunostimulatory in vivo and could be useful as an adjuvant.
-
Abnormal development of zebrafish after knockout and knockdown of ribosomal protein L10a Reviewed
Palasin, K., Uechi, T., Yoshihama, M., Srisowanna, N., Choijookhuu, N., Hishikawa, Y., Kenmochi, N., Chotigeat, W.
Scientific Reports 2019.12
Language：English Publishing type：Research paper (scientific journal)
-
Zebrafish models of Diamond-Blackfan anemia: A tool for understanding the disease pathogenesis and drug discovery Reviewed
Uechi T, Kenmochi N
Pharmaceuticals 2019.10
Language：English Publishing type：Research paper (scientific journal)
-
A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS Reviewed
McMahon M, Contreras A, Holm M, Uechi T, Forester CM, Pang X, Jackson C, Calvert ME, Chen B, Quigley DA, Luk JM, Kelley RK, Gordan JD, Gill RM, Blanchard SC, Ruggero D
eLife 2019.9
Language：English Publishing type：Research paper (scientific journal)
DOI： 10.7554/eLife.48847
Books 【 display / non-display 】
-
The role of alternative mRNA splicing in heart development
Bittel D.C., Kibiryeva N., Kenmochi N., Patil P., Uechi T., Rongish B., Filla M., Marshall J., Artman M., Johnson R., O’Brien J.E.（ Role： Sole author）
Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension 2020.1 （ ISBN:9789811511844 ）
Language：Japanese
Research in the last 10 years has led to improved understanding of the genetic regulation of vertebrate heart development, but despite this effort, approximately 70% of all congenital heart defects (CHDs) still have an unknown etiology. Alternative splicing of mRNA has been documented to play roles in normal and abnormal development. Dysregulated splicing of mRNA has been shown to cause heart defects in mice, however a link between mRNA splicing and CHDs has not yet been shown in humans. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF) relative to the RV of normally developing infants. Moreover, there was a significant decrease in the level of 12 scaRNAs (small cajal body associated RNAs) in the RV from infants with TOF. These small noncoding RNAs guide the biochemical modification of specific nucleotides in spliceosomal RNAs that are critical for spliceosomal function. We used primary cells derived from the RV of infants with TOF to show a direct link between scaRNA levels and alteration in mRNA splicing of several genes that regulate heart development. We modified the expression of sets of scaRNAs and consequentially documented distinctive mRNA splicing, accompanied by corresponding protein isoform changes suggesting a unique contribution by each scaRNA. Furthermore, we knocked down two homologous scaRNAs in zebrafish and saw a disruption of heart development with an accompanying alteration in splice isoforms of cardiac regulatory genes. These combined results provide compelling evidence that scaRNAs contribute to the regulation of cardiac development by fine-tuning the fidelity of the spliceosome that adjusts exon retention as cell differentiation occurs. Importantly, our findings are consistent with the concept that disruption of mRNA splicing patterns during early embryonic development disturbs normal signaling pathways, resulting in conotruncal misalignment and TOF.
-
大・中・小動物実験プロトコル
宮崎大学動物実験プロトコール編集委員会（ Role： Sole author）
宮日文化情報センター 2016.3
Language：Japanese Book type：Scholarly book
MISC 【 display / non-display 】
-
Development of a zebrafish model of congenital anemia and drug screening
Kenmochi Naoya, Uechi Tamayo, Yoshihama Maki
The Japanese Journal of Pediatric Hematology / Oncology 56 ( 5 ) 402 - 406 2019
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution) Publisher：The Japanese Society of Pediatric Hematology / Oncology
Diamond–Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by diminished numbers of erythroid progenitors. Although it is known that the ribosome is involved in the DBA onset, the molecular pathogenesis of this disease remains unknown and there are no clinically effective treatments available. We developed a zebrafish model of DBA and analyzed the pathogenic mechanism of this disease using this model. Zebrafish has many advantages in studying disease mechanisms, including the fast development and transparency of its embryos and its features conserved in humans. In addition, <i>in vivo</i> chemical screenings enable us to efficiently identify drug candidates. In this review, we introduce our approach to understand the pathogenic mechanism of DBA and to discover drug candidates using zebrafish as an animal model.
-
リボソームタンパク質と翻訳制御
上地珠代, 剣持直哉
生体の科学：細胞の分子構造と機能－核以外の細胞小器官 63 ( 5 ) 362 - 363 2012.10
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution) Publisher：医学書院
-
上地 珠代, 剣持 直哉
遺伝子医学mook 15 79 - 84 2009.11
Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution) Publisher：メディカルドゥ
Presentations 【 display / non-display 】
-
Translational efficiency of mRNAs required for hematopoiesis were decreased in a zebrafish model of Diamond-Blackfan anemia
Tamayo Uechi, Mariko Nagatomo, Yukari Nakajima, Maki Yoshihama, Yutaka Suzuki, Naoya Kenmochi
MBSJ2023 2023.12.8
Event date： 2023.12.6 - 2023.12.8
Language：English Presentation type：Poster presentation
-
Translational efficiency of mRNAs required for hematopoiesis were decreased in a zebrafish model of Diamond-Blackfan anemia International conference
Tamayo Uechi, Mariko Nagatomo, Yutaka Suzuki, Naoya Kenmochi
Toward understanding of Mechanisms of human diseases: Challenges using model organisms 2023 2023.11.10
Event date： 2023.11.9 - 2023.11.10
Language：English Presentation type：Poster presentation
-
Depletion of ribosomal proteins and mRNA-specific translation control: studying the molecular pathogenesis of congenital anemia using zebrafish Invited
2022.12.1
Event date： 2022.11.30 - 2022.12.2
Language：Japanese Presentation type：Oral presentation (invited, special)
-
Exploring the molecular pathogenesis of ribosomopathies using zebrafish disease models Invited
2022.12.2
Event date： 2022.11.30 - 2022.12.2
Presentation type：Oral presentation (general)
-
リボソームの異常と疾患〜未知の翻訳機構の解明をめざす〜 Invited
上地珠代
慶應義塾大学先端研究セミナー 2022.10.18
Event date： 2022.10.18
Language：Japanese Presentation type：Public lecture, seminar, tutorial, course, or other speech
Grant-in-Aid for Scientific Research 【 display / non-display 】
-
J-RDMMによる小型モデル生物を用いた希少・未診断疾患のin vivo解析
Grant number：23ek0109650s0601 2023.09 - 2024.03
AMED AMED研究費 IRUD beyond分野
Authorship：Principal investigator
-
mRNA選択的な翻訳制御機構の解明 International coauthorship
Grant number：16KK0185 2017.11 - 2020.03
科学研究費補助金 国際共同研究加速基金（国際共同研究強化）
-
自己免疫とＲＮＡ修飾：全身性エリテマトーデス発症の分子機構 研究課題
Grant number：20200070 2008.04 - 2010.03
科学研究費補助金 新学術領域研究（研究課題提案型）
-
翻訳後修飾としてのチロシン硫酸化の空間および時間的制御機構の理解と機能解明
Grant number：22H02262 2022.04 - 2026.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
榊原 陽一、
Authorship：Coinvestigator(s)
-
病態脳における小胞体プロテオスタシス破綻によるコレステロール合成不全と脳委縮
Grant number：22H02954 2022.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(B)
Authorship：Coinvestigator(s)
Available Technology 【 display / non-display 】
-
ゼブラフィッシュを用いた先天性貧血の発症機序の解明
希少疾患のゼブラフィッシュモデルの作製と解析
創薬のためのin vivo化合物スクリーニングRelated fields where technical consultation is available：ゼブラフィッシュの疾患モデルの作製（遺伝子ノックダウン、ゲノム編集による変異体作出）
ゼブラフィッシュ胚を用いた化合物ライブラリーのスクリーニングMessage：ゼブラフィッシュを用いることで、様々な遺伝子のin vivoでの機能解析を手軽に始めることができます。