Stories

A Warm Welcome to Our New PhD Students!

August 14, 2019

New semester, new beginnings! – CSI Singapore warmly welcomed 8 new PhD students who joined our graduate program in Cancer Biology on 1st August 2019. The PhD program, offered by CSI Singapore, is designed to support graduate students working to advance discoveries in cancer research. These students will undergo a rigorous five-year academic and research program. […]

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Aug 14, 2019 Celine Tam 0 comments
Congratulations to the Class of 2019!

August 14, 2019

Congratulations to the graduates of the PhD Graduate Program in Cancer Biology! On 23rd July 2019, CSI Singapore organized a Graduate Tea Party in honour of the Class of 2019. After years of dedication and hard work, our graduates and their supervisors gathered to celebrate this significant milestone, which marks the end of their PhD journey […]

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Aug 14, 2019 Celine Tam 0 comments
SNAI1 recruits HDAC1 to suppress SNAI2 transcription during epithelial to mesenchymal transition. (Sci Rep, Jun 2019)

August 2, 2019

Sundararajan V1, Tan M1, Tan TZ1, Ye J1, Thiery JP2,3,4,5, Huang RY6,7,8,9. Author Information 1Cancer Science Institute of Singapore, National University of Singapore, Center for Translational Medicine, 14 Medical Drive, MD6 #12-01, 117599, Singapore, Singapore. 2Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, MD7, #02-03, Singapore, 117597, Singapore. 3Guangzhou Institute of Biomedicine […]

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Aug 02, 2019 Celine Tam 0 comments
Super-enhancers: critical roles and therapeutic targets in hematologic malignancies. (J Hematol Oncol, Jul 2019)

August 2, 2019

Jia Y1,2, Chng WJ1,3,4, Zhou J5,6. Author Information 1Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Centre for Translational Medicine, Singapore, 117599, Republic of Singapore. 2Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang, China. 3Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, […]

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Aug 02, 2019 Celine Tam 0 comments
Inflated performance measures in enhancer-promoter interaction-prediction methods. (Nat Genet, Jul 2019)

August 2, 2019

Cao F1, Fullwood MJ2,3,4. Author Information 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. mfullwood@ntu.edu.sg. 3School of Biological Sciences, Nanyang Technological University, Singapore, Singapore. mfullwood@ntu.edu.sg. 44Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. mfullwood@ntu.edu.sg.   […]

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Aug 02, 2019 Celine Tam 0 comments
A Heartfelt Thank You to Our Donor, Mr Sim Chee Meng

July 8, 2019

CSI Singapore would like to extend a heartfelt thank you to our donor, Mr Sim Chee Meng for his giving. The institute is devoted to fostering ground-breaking research and developing cancer therapies. Over the years, the generous support of our donors has been fundamental in supporting the institute in its mission to advance knowledge, foster […]

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Jul 08, 2019 Celine Tam 0 comments
CSI Student Receives Gold Award at the Singapore Science and Engineering Fair (SSEF) 2019 Ceremony

June 28, 2019

Congratulations to Shamill Amedot Udonwa, attachment student from Prof. Chng Wee Joo’s laboratory, who clinched the Gold Award at the Singapore Science and Engineering Fair (SSEF) 2019, held from 6th-7th March 2019 at the Community Auditorium, Our Tampines Hub. Organized by the Ministry of Education (MOE), the Agency for Science, Technology and Research (A*STAR) and […]

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Jun 28, 2019 Celine Tam 0 comments
DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells. (Nucleic Acids Res, Jun 2019)

June 28, 2019

Tan HK1,2, Wu CS1, Li J1,3, Tan ZH1, Hoffman JR4, Fry CJ4, Yang H1, Di Ruscio A5,6, Tenen DG1,6. Author Information 1Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599. 2National University of Singapore Graduate School for Integrative Sciences and Engineering, 21 Lower Kent Ridge, Singapore 119077. 3Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College […]

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Jun 28, 2019 Celine Tam 0 comments
[Review] Beginning of a New Era: Mapping the Bone Marrow Niche. (Cell, Jun 2019)

June 28, 2019

Nakamura-Ishizu A1, MacArthur BD2, Suda T3. Author Information 1Cancer Science Institute, National University of Singapore, 14 Medical Drive, MD6, 117599, Singapore; International Research Center for Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto City 860-0811, Japan. 2International Research Center for Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto City 860-0811, Japan; Mathematical Sciences, University of Southampton, Southampton […]

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Jun 28, 2019 Celine Tam 0 comments
FBXW5 Promotes Tumorigenesis and Metastasis in Gastric Cancer via Activation of the FAK-Src Signaling Pathway. (Cancers (Basel), Jun 2019)

June 28, 2019

Yeo MS1, Subhash VV2,3, Suda K4, Balc?o?lu HE5, Zhou S6, Thuya WL7, Loh XY8, Jammula S9, Peethala PC10, Tan SH11, Xie C12, Wong FY13, Ladoux B14,15, Ito Y16, Yang H17, Goh BC18,19, Wang L20, Yong WP21,22. Author Information 1Department of Haematology-Oncology, National University Hospital of Singapore, Singapore 119228, Singapore. e0222965@u.nus.edu. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore. vinod.v@unsw.edu.au. 3Lowy Cancer Research Centre, University of New South Wales, […]

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Jun 28, 2019 Celine Tam 0 comments
The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia. (Blood, May 2019)

May 22, 2019

Tan SH1, Leong WZ2, Ngoc PCT3, Tan TK4, Bertulfo FC5, Lim MC6, An O7, Li Z8, Yeoh AEJ8, Fullwood MJ9, Tenen DG10, Sanda T11. Author Information 1Cancer Science Institute, National University of Singapore, Singapore. 2Cancer Science Institute of Singapore, National Univeristy of Singapore, Singapore. 3Cancer Science Institute of Singapore, National University of Singapore, Sweden. 4Cancer Science Institute of Singapore, National University of Singapore. 5Cancer Science Institute […]

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May 22, 2019 Celine Tam 0 comments
LNK suppresses interferon signaling in melanoma. (Nat Comm, May 2019)

May 22, 2019

Ling-Wen Ding1, Qiao-Yang Sun1, Jarem J.Edwards2,3, Lucia Torres Fernández1, Xue-Bin Ran1, Si-Qin Zhou1, Richard A. Scolyer2,3,4, James S. Wilmott2,3, John F. Thompson2,3,4, Ngan Doan5, Jonathan W. Said5, Nachiyappan Venkatachalam1, Jin-Fen Xiao1, Xin-Yi Loh1, Maren Pein1, Liang Xu1, David W. Mullins6, Henry Yang1, De-Chen Lin7 & H. Phillip Koeffler 1,7 Author Information 1Cancer Science Institute of […]

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May 22, 2019 Celine Tam 0 comments
HNF4a pathway mapping identifies wild-type IDH1 as a targetable metabolic node in gastric cancer. (Gut, May 2019)

May 22, 2019

Xu C#1,2, Ooi WF#3, Qamra A3,4, Tan J5,6, Chua BY7, Ho SWT1,2, Das K2, Adam Isa ZF2, Li Z5, Yao X8, Yan T2, Xing M2,4, Huang KK2, Lin JS3, Nandi T3, Tay ST2, Lee MH2, Tan ALK2, Ong X2, Ashktorab H9, Smoot D10, Li S2,11, Ng SC7, Teh BT1,2,5,8,11, Tan P1,2,3,12,13,14. Author information 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. 2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore. 3Cancer Therapeutics and Stratified […]

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May 22, 2019 Celine Tam 0 comments
Congratulations to Our Long Service Award 2019 Recipients!

May 2, 2019

The Long Service Awards were presented to employees in recognition for their valued contributions and dedicated service to CSI. A total of 13 recipients have been conferred the Long Service Award for their 5 and 10 years of service respectively. CSI Singapore would like to congratulate the following recipients – Five Years of Service  Cao […]

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May 02, 2019 Celine Tam 0 comments
CSI Research Fellow Presents Advances in Cancer Research at AACR Annual Meeting 2019

May 2, 2019

Darren Tan, a recent graduate from the CSI Ph.D. Graduate Scholarship program who was under the mentorship of Prof. Toshio Suda, was given the honor to present his work on the impact of PRMT5 inhibition on blood stem cells at this year’s American Association for Cancer Research (AACR) Annual Meeting. Darren’s attendance at the 2019 […]

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May 02, 2019 Celine Tam 0 comments
Identification of a novel enhancer of CEBPE essential for granulocytic differentiation. (Blood, Apr 2019)

May 2, 2019

Shyamsunder P1, Shanmugasundaram M2, Mayakonda A3, Dakle P4, Teoh WW5, Han L6, Kanojia D7, Lim MC8, Fullwood M9, An O10, Yang H11, Jizhong S12, Hossain MZ13, Madan V3, Koeffler HP6. Author information 1Cancer Science Institute of Singapore, Singapore csips@nus.edu.sg. 2Cancer Science Institite of SIngapore. 3Cancer Science Institute of Singapore, Singapore. 4Cancer Science Institute of Singapore, National University of Singapore, Singapore. 5National University of Singapore, Cancer Science Institute of Singapore, […]

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May 02, 2019 Celine Tam 0 comments
Molecular pathogenic pathways in extranodal NK/T cell lymphoma. (J Hematol Oncol, Apr 2019)

May 2, 2019

de Mel S1, Hue SS2,3, Jeyasekharan AD1,4, Chng WJ5,6, Ng SB7,8,9. Author information 1Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, 1E Kent Ridge Rd, Singapore, 119228, Singapore. 2Department of Pathology, National University Health System, Singapore, Singapore. 3Agency for Science Technology and Research Singapore, Institute of Molecular and Cellular Biology, Singapore, Singapore. 4Cancer Science Institute of […]

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May 02, 2019 Celine Tam 0 comments
Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma. (Nat Commun, Mar 2019)

May 2, 2019

Chen Y1, Xu L2, Mayakonda A1, Huang ML1,3, Kanojia D1, Tan TZ1, Dakle P1, Lin RY1, Ke XY1, Said JW4, Chen J5, Gery S6, Ding LW1, Jiang YY1, Pang A7, Puhaindran ME7,8,9, Goh BC1,7,10, Koeffler HP1,6,7. Author information 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore. csixl@nus.edu.sg. 3School of Biology and Basic Medical Sciences, Soochow University, […]

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May 02, 2019 Celine Tam 0 comments
Prestigious STaR Award Renewed for Prof Toshio Suda

April 29, 2019

Find out more about Prof. Suda’s first STaR award in 2014 here: https://www.csi.nus.edu.sg/web/prestigious-star-award-for-translational-research-awarded-to-two-csi-pis   Find out more about the NMRC awards here: http://www.nmrc.gov.sg/grants/talent-development/stria

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Apr 29, 2019 Karol Chia 0 comments
PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells. (Cell Rep, Feb 2019)

April 1, 2019

Tan DQ1, Li Y1, Yang C1, Li J1, Tan SH1, Chin DWL2, Nakamura-Ishizu A1, Yang H1, Suda T3.

Author information

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
2Department of Medicine, Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
3Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

Abstract

Protein arginine methyltransferase 5 (PRMT5) is essential for hematopoiesis, while PRMT5 inhibition remains a promising therapeutic strategy against various cancers. Here, we demonstrate that hematopoietic stem cell (HSC) quiescence and viability are severely perturbed upon PRMT5 depletion, which also increases HSC size, PI3K/AKT/mechanistic target of rapamycin (mTOR) pathway activity, and protein synthesis rate. We uncover a critical role for PRMT5 in maintaining HSC genomic integrity by modulating splicing of genes involved in DNA repair. We found that reducing PRMT5 activity upregulates exon skipping and intron retention events that impair gene expression. Genes across multiple DNA repair pathways are affected, several of which mediate interstrand crosslink repair and homologous recombination. Consequently, loss of PRMT5 activity leads to endogenous DNA damage that triggers p53 activation, induces apoptosis, and culminates in rapid HSC exhaustion, which is significantly delayed by p53 depletion. Collectively, these findings establish the importance of cell-intrinsic PRMT5 activity in HSCs.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

KEYWORDS:
DNA damage; RNA; genomic integrity; hematopoietic stem cells; protein arginine methyltransferase 5; proteostasis; splicing

PMID: 30811983

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Apr 01, 2019 Karol Chia 0 comments