Stories

Reversing Cancer-Causing Faults in the Breast Cancer Gene BRCA2.

May 20, 2021

Inherited faults (‘mutations’) in the breast cancer gene, BRCA2, can lead to cancers of the breast, ovary or other organs. BRCA2 codes for a protein containing 3,418 building blocks (called ‘amino acids’) in human cells. Surprisingly, certain BRCA2 mutations that cause cancer affect just a single building-block out of over three thousand. Ashok Venkitaraman’s laboratory […]

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May 20, 2021 Celine Tam 0 comments
Congratulations to Dr. Polly Chen on her promotion to Associate Professor!

May 12, 2021

CSI Singapore is proud to announce the promotion of Dr. Polly Chen to Associate Professor! Dr. Chen joined CSI Singapore in 2014 as a Principal Investigator. Since then, she has received multiple awards in recognition of her outstanding research, including the EMBO Young Investigator Program (YIP) and the Yong Loo Lin School of Medicine Young Researcher Of the Year Award.

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May 12, 2021 Celine Tam 0 comments
Prolonged Maintenance of Hematopoietic Stem Cells that Escape From Thrombopoietin Deprivation. (Blood, Mar 2021)

April 27, 2021

Hematopoietic stem cells (HSC) rarely divide, rest in quiescence and proliferate only upon stress hematopoiesis. The cytokine thrombopoietin (Thpo) has been perplexingly described to induce quiescence and promote self-renewal divisions in HSCs. In order to clarify the contradictory effect of Thpo, we conducted a detailed analysis on conventional (Thpo-/-) and liver-specific (Thpofl/fl;AlbCre+/-) Thpo deletion models. Thpo-/- HSCs exhibited profound loss of quiescence, impaired cell cycle progression and increased apoptosis.

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Apr 27, 2021 Celine Tam 0 comments
Quantitative Imaging of RAD51 Expression as a Marker of Platinum Resistance in Ovarian Cancer. (EMBO Mol Med, Mar 2021)

April 27, 2021

Early relapse after platinum chemotherapy in epithelial ovarian cancer (EOC) portends poor survival. A-priori identification of platinum resistance is therefore crucial to improve on standard first-line carboplatin-paclitaxel treatment. The DNA repair pathway homologous recombination (HR) repairs platinum-induced damage, and the HR recombinase RAD51 is overexpressed in cancer. We therefore designed a REMARK-compliant study of pre-treatment RAD51 expression in EOC, using fluorescent quantitative immunohistochemistry (qIHC) to overcome challenges in quantitation of protein expression in situ.

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Apr 27, 2021 Celine Tam 0 comments
Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer. (Commun Biol, Apr 2021)

April 27, 2021

Lung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencing in aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer.

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Apr 27, 2021 Celine Tam 0 comments
USD 45M Series B Funding for UK-Based Biopharmaceutical Company’s Drug Discovery Programmes

April 19, 2021

The pathways that control the behaviour of cells are complex, non-linear and highly redundant. As such, identifying the right molecular target for the development of next-generation drugs is oftentimes akin to looking for a needle in a haystack. Ashok Venkitaraman’s laboratory developed a novel approach termed “Protein-interference” or “Protein-i” to hunt for new drug targets, which was spun out in 2016 by University of Cambridge into the biotech company PhoreMost, with Dr. Venkitaraman as co-founder.

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Apr 19, 2021 Celine Tam 0 comments
Novel First-in-Class Drug Discovery Approach is Breaking New Ground in Anti-Cancer Therapeutics

April 19, 2021

ATP-hydrolyzing enzymes like protein kinases are major drug targets for oncology. Drugs that inhibit these enzymes typically engage their ATP-binding (active) sites to inhibit catalysis. However, these active sites are structurally similar to one another, especially in enzymes belonging to the same family, making it difficult to develop drugs that are highly selective with reduced off-target effects. Ashok Venkitaraman’s laboratory has systematically developed a different approach to this problem – termed ‘allo-targeting’.

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Apr 19, 2021 Celine Tam 0 comments
Cancer drug may be able to treat inflammation caused by COVID-19 virus, Singapore-US study shows

April 13, 2021

CSI Principal Investigator, Dr. Anand Jeyasekharan, was recently involved in a pioneering study performed by the Icahn School of Medicine at Mount Sinai in the United States and the National University Cancer Institute, Singapore (NCIS). Findings from this study revealed that Topotecan, a chemotherapeutic drug, can reduce the severity and death rates of infection by SARS-CoV-2 and may potentially be used to treat patients with moderate to severe forms of Covid-19.

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Apr 13, 2021 Celine Tam 0 comments
Congratulations to Our Long Service Award 2021 Recipients!

April 8, 2021

The Long Service Awards were presented to employees in appreciation for their valued contributions and dedicated service to NUS. A total of 13 recipients have been conferred the Long Service Award for their 5, 10, 15 and 20 years of service respectively. CSI Singapore would like to congratulate and thank the following recipients for their […]

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Apr 08, 2021 Celine Tam 0 comments
CSI Research Fellow Receives International Myeloma Society (IMS) and Paula and Rodger Riney Foundation Career Development Award

April 7, 2021

Congratulations to Dr. Teoh Phaik Ju, Research Fellow from Prof. Chng Wee Joo’s lab, who has recently been awarded the prestigious International Myeloma Society (IMS) and Paula and Rodger Riney Foundation Career Development Award for her outstanding research proposal.

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Apr 07, 2021 Celine Tam 0 comments
Researchers Unravel Novel Insights on Hematopoietic Stem Cell (HSC) Maintenance and its Mechanism Under Thrombopoietin (Thpo) Deficiency

April 6, 2021

In this study, a team of researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS), the International Research Center for Medical Sciences (IRCMS) at the Kumamoto University and the Tokyo Women’s Medical University (TWMU) investigated the maintenance of HSCs in quiescence as well as its association with cytokine Thrombopoietin (Thpo).

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Apr 06, 2021 Celine Tam 0 comments
NUS Medicine Awards 2020

March 19, 2021

Dr. Chong Shu Yun Phyllis and Dr. Teoh Phaik Ju were awarded by A/Prof. Kevin Tan, Vice-Dean of Graduate Studies Congratulations to Dr. Teoh Phaik Ju and Dr. Chong Shu Yun Phyllis, who were honoured for their research achievements at the NUS Medicine Awards 2020 Ceremony. The award ceremony recognises and celebrates the success and […]

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Mar 19, 2021 Celine Tam 0 comments
Epigenetics in Cancer Symposium 2021

March 12, 2021

The Epigenetics in Cancer Symposium 2021 has concluded successfully! Jointly organized by the Cancer Science Institute of Singapore, NUS and the Université de Paris, the symposium drew an overwhelming turnout of 442 participants hailing from 32 countries. This inaugural symposium boasted an impressive line-up of speakers, including keynote speaker, Dr. Geneviève Almouzni from the Institut Curie, Paris.

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Mar 12, 2021 Celine Tam 0 comments
“3G” Trial: An RNA Editing Signature to Guide Gastric Cancer Chemotherapy. (Cancer Res, Feb 2021)

March 12, 2021

Gastric cancer (GC) cases are often diagnosed at an advanced stage with poor prognosis. Platinum-based chemotherapy has been internationally accepted as first-line therapy for inoperable or metastatic GC. To achieve greater benefits, selection of patients eligible for this treatment is critical. Although gene expression profiling has been widely used as a genomic classifier to identify molecular subtypes of GC and to stratify patients for different chemotherapy regimens, its prediction accuracy can be improved.

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Mar 12, 2021 Celine Tam 0 comments
H3K27me3-rich Genomic Regions Can Function as Silencers to Repress Gene Expression via Chromatin Interactions. (Nat Commun, Jan 2021)

March 12, 2021

The mechanisms underlying gene repression and silencers are poorly understood. Here we investigate the hypothesis that H3K27me3-rich regions of the genome, defined from clusters of H3K27me3 peaks, may be used to identify silencers that can regulate gene expression via proximity or looping. We find that H3K27me3-rich regions are associated with chromatin interactions and interact preferentially with each other.

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Mar 12, 2021 Celine Tam 0 comments
MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma. (Oncogene, Feb 2021)

March 12, 2021

Soft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E).

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Mar 12, 2021 Celine Tam 0 comments
Short H2A histone variants are expressed in cancer. (Nat Commun, Jan 2021)

February 4, 2021

Short H2A (sH2A) histone variants are primarily expressed in the testes of placental mammals. Their incorporation into chromatin is associated with nucleosome destabilization and modulation of alternate splicing. Here, we show that sH2As innately possess features similar to recurrent oncohistone mutations associated with nucleosome instability.

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Feb 04, 2021 Celine Tam 0 comments
Capitalizing on Synthetic Lethality of MYC to Treat Cancer in the Digital Age. (Trends Pharmacol Sci, Jan 2021)

February 4, 2021

Deregulation of MYC is among the most frequent oncogenic drivers of cancer. Developing targeted therapies against MYC is, therefore, one of the most critical unmet needs of cancer therapy. Unfortunately, MYC has been labelled as undruggable due to the lack of success in developing clinically relevant MYC-targeted therapies. Synthetic lethality is a promising approach that targets MYC-dependent vulnerabilities in cancer.

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Feb 04, 2021 Celine Tam 0 comments
ZNF143 mediates CTCF-bound promoter-enhancer loops required for murine hematopoietic stem and progenitor cell function. (Nat Commun, Jan 2021)

February 4, 2021

CCCTC binding factor (CTCF) is an important factor in the maintenance of chromatin-chromatin interactions, yet the mechanism regulating its binding to chromatin is unknown. We demonstrate that zinc finger protein 143 (ZNF143) is a key regulator for CTCF-bound promoter-enhancer loops. In the murine genome, a large percentage of CTCF and ZNF143 DNA binding motifs are distributed 37 bp apart in the convergent orientation.

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Feb 04, 2021 Celine Tam 0 comments
Iqgap3-Ras axis drives stem cell proliferation in the stomach corpus during homoeostasis and repair. (Gut, Dec 2020)

December 28, 2020

Tissue stem cells are central regulators of organ homoeostasis. We looked for a protein that is exclusively expressed and functionally involved in stem cell activity in rapidly proliferating isthmus stem cells in the stomach corpus. Results revealed that IQGAP3 is a major regulator of stomach epithelial tissue homoeostasis and repair. The upregulation of IQGAP3 in gastric cancer suggests that IQGAP3 plays an important role in cancer cell proliferation.

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Dec 28, 2020 Celine Tam 0 comments