Latest Happenings

CSI Principal Investigator and Senior Research Scientist Receive Awards at the Asian Fund for Cancer Research’s (AFCR) 2021 BRACE Award Venture Competition

May 5, 2022

Congratulations to A/Prof. Edward Kai-Hua Chow and Dr. Bee Hui Liu, who have recently won awards at the Asian Fund for Cancer Research’s (AFCR) 2021 BRACE Award Venture Competition, a first-of-its-kind program for early-stage oncology technology companies focused on Asian-prevalent cancers.

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May 05, 2022 Celine Tam 0 comments
Phase Ib/II Dose Expansion Study of Lenvatinib Combined with Letrozole in Post-Menopausal Women with Hormone Receptor Positive Breast Cancer (Clin Cancer Res, Apr 22)

May 5, 2022

RET is an estrogen response gene with preclinical studies demonstrating cross talk between RET and estrogen receptor (ER) pathways. We investigate the role of lenvatinib, a multi-kinase inhibitor with potent activity against RET, in patients with metastatic breast cancer.

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May 05, 2022 Celine Tam 0 comments
Non-Coding RNA LEVER Sequestration of PRC2 Can Mediate Long Range Gene Regulation (Commun Biol, Apr 22)

May 5, 2022

Polycomb Repressive Complex 2 (PRC2) is an epigenetic regulator required for gene silencing during development. Although PRC2 is a well-established RNA-binding complex, the biological function of PRC2-RNA interaction has been controversial. Here, we study the gene-regulatory role of the inhibitory PRC2-RNA interactions. We report a nuclear long non-coding RNA, LEVER, which mapped 236 kb upstream of the ?-globin cluster as confirmed by Nanopore sequencing.

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May 05, 2022 Celine Tam 0 comments
Multilayered Control of Splicing Regulatory Networks by DAP3 Leads to Widespread Alternative Splicing Changes in Cancer. (Nat Commun, Apr 22)

May 5, 2022

The dynamic regulation of alternative splicing requires coordinated participation of multiple RNA binding proteins (RBPs). Aberrant splicing caused by dysregulation of splicing regulatory RBPs is implicated in numerous cancers. Here, we reveal a frequently overexpressed cancer-associated protein, DAP3, as a splicing regulatory RBP in cancer.

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May 05, 2022 Celine Tam 0 comments
CSI Singapore Researchers Uncover Role of ADARs and its Implications in Cancer Development

May 4, 2022

In a novel step forward, A/Prof. Polly Chen and her team embarked on a study to better understand the role of crosstalk between RNA editing machinery (ADAR proteins) and circRNA biogenesis machinery in cancer. Findings from this interesting study will provide new insights that can contribute to the development of effective therapeutic approaches utilizing ADARs-regulated circRNAs, given their high stability and diverse functions.

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May 04, 2022 Celine Tam 0 comments
PLK1 Inhibition Selectively Induces Apoptosis in ARID1A Deficient Cells Through Uncoupling of Oxygen Consumption from ATP Production. (Oncogene, Mar 22)

April 6, 2022

Inhibitors of the mitotic kinase PLK1 yield objective responses in a subset of refractory cancers. However, PLK1 overexpression in cancer does not correlate with drug sensitivity, and the clinical development of PLK1 inhibitors has been hampered by the lack of patient selection marker. Using a high-throughput chemical screen, we discovered that cells deficient for the tumor suppressor ARID1A are highly sensitive to PLK1 inhibition.

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Apr 06, 2022 Celine Tam 0 comments
Clinical Translation of Patient-Derived Tumour Organoids- Bottlenecks and Strategies. (Biomark Res, Mar 22)

April 6, 2022

Multiple three-dimensional (3D) tumour organoid models assisted by multi-omics and Artificial Intelligence (AI) have contributed greatly to preclinical drug development and precision medicine. The intrinsic ability to maintain genetic and phenotypic heterogeneity of tumours allows for the reconciliation of shortcomings in traditional cancer models. While their utility in preclinical studies have been well established, little progress has been made in translational research and clinical trials. In this review, we identify the major bottlenecks preventing patient-derived tumour organoids (PDTOs) from being used in clinical setting.

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Apr 06, 2022 Celine Tam 0 comments
ADARs act as potent regulators of circular transcriptome in cancer (Nat Commun, Mar 2022)

April 6, 2022

Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function.

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Apr 06, 2022 Celine Tam 0 comments
CSI Singapore Researchers Discover Achilles Heel of High-Risk Multiple Myeloma (MM) Patients

April 6, 2022

Chromosomal abnormalities are found in most multiple myeloma (MM) patients. While myeloma patients have generally benefited from the advancement of treatment modalities over the years, the treatment outcome for patients having 2 or more high-risk prognostic events remains poor. In a novel step forward, researchers from Prof. Chng Wee Joo’s laboratory embarked on a study which aims to address the unmet clinical need in this group of patients.

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Apr 06, 2022 Celine Tam 2 comments
MYC overexpression leads to increased chromatin interactions at superenhancers and MYC binding sites. (Genome Res, Feb 2022)

March 7, 2022

The MYC oncogene encodes for the MYC protein and is frequently dysregulated across multiple cancer cell types, making it an attractive target for cancer therapy. MYC overexpression leads to MYC binding at active enhancers, resulting in a global transcriptional amplification of active genes. Since superenhancers are frequently dysregulated in cancer, we hypothesized that MYC preferentially invades into superenhancers and alters the cancer genome organization.

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Mar 07, 2022 Celine Tam 0 comments
p53-NEIL1 co-abnormalities induce genomic instability and promote synthetic lethality with Chk1 inhibition in multiple myeloma having concomitant 17p13(del) and 1q21(gain). (Oncogene, Feb 2022)

March 7, 2022

17p13(del) and 1q21(gain) are critical and independent high-risk cytogenetic markers, however, the biological significance underlying the poor outcome in MM patients having co-occurrence of both these chromosomal aberrations has never been interrogated. Herein, we identified that patients harbouring concomitant 17p13(del) with 1q21(gain) demonstrated the worst prognosis as compared to patients with single- (either 17p13(del) or 1q21(gain)) and with no chromosomal events (WT for both chromosomal loci); and they are highly enriched for genomic instability (GI) signature.

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Mar 07, 2022 Celine Tam 0 comments
Global analysis of RNA-binding proteins identifies a positive feedback loop between LARP1 and MYC that promotes tumorigenesis. (Cell Mol Life Sci, Feb 2022)

March 7, 2022

In addition to genomic alterations, aberrant changes in post-transcriptional regulation can modify gene function and drive cancer development. RNA-binding proteins (RBPs) are a large class of post-transcriptional regulators that have been increasingly implicated in carcinogenesis. By integrating multi-omics data, we identify LARP1 as one of the most upregulated RBPs in colorectal cancer (CRC) and demonstrate its oncogenic properties.

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Mar 07, 2022 Celine Tam 0 comments
Uncover the Mysterious, Culpable “Super-Enhancers” in Aggressive Blood Cancer

February 9, 2022

Multiple myeloma (MM) is the second most common blood cancer and remains an incurable disease. In a novel step forward, Prof. Chng Wee Joo’s group identified the mysterious and culpable “super-enhancers” in MM. By performing epigenomic enhancer profiling, findings established HJURP as an SE-associated gene of t(4;14)-positive multiple myeloma. This study highlights the potential of super enhancer profiling as an efficient platform to stamp out MM as well as other types of cancer.

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Feb 09, 2022 Celine Tam 0 comments
ChIP-AP: An Integrated Analysis Pipeline for Unbiased ChIP-seq Analysis. (Brief Bioinform, Jan 2022)

February 3, 2022

Chromatin immunoprecipitation coupled with sequencing (ChIP-seq) is a technique used to identify protein-DNA interaction sites through antibody pull-down, sequencing and analysis; with enrichment 'peak' calling being the most critical analytical step. Benchmarking studies have consistently shown that peak callers have distinct selectivity and specificity characteristics that are not additive and seldom completely overlap in many scenarios, even after parameter optimization. We therefore developed ChIP-AP, an integrated ChIP-seq analysis pipeline utilizing four independent peak callers, which seamlessly processes raw sequencing files to final result.

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Feb 03, 2022 Celine Tam 0 comments
A Point Mutation R122C in RUNX3 Promotes the Expansion of Isthmus Stem Cells and Inhibits Their Differentiation in the Stomach. (Cell Mol Gastroenterol Hepatol, Jan 2022)

February 3, 2022

RUNX3R122C missense mutation is associated with the continuous cycling of isthmus stem/progenitor cells, maturation arrest and development of a precancerous state. This work highlights the importance of RUNX3 in prevention of metaplasia and gastric cancer.

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Feb 03, 2022 Celine Tam 0 comments
MiR-138 is a Potent Regulator of the Heterogenous MYC Transcript Population in Cancers. (Oncogene, Dec 2021)

February 3, 2022

In this study, we demonstrate that the MYC 3'UTR is shortened in colorectal cancer (CRC). Using unbiased computational and experimental approaches, we identify and validate microRNAs that target the MYC coding region. In particular, we show that miR-138 inhibits MYC expression and suppresses tumor growth of CRC and hepatocellular carcinoma (HCC) cell lines.

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Feb 03, 2022 Celine Tam 0 comments
NUS researchers identify novel pathways responsible for liver cancer

January 28, 2022

In this ground-breaking study helmed by Prof. Daniel Tenen and Dr. Yvonne Tay, the identification of new molecular pathways responsible for liver cancer could open up avenues for the development of novel therapeutic approaches for HCC patients.

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Jan 28, 2022 Celine Tam 0 comments
A Heartfelt Thank You to Our Donor, the late Mdm Chee Ung Ha

January 5, 2022

  CSI Singapore would like to express a heartfelt thank you to our donor, the late Mdm Chee Ung Ha for her generous gift of SGD200,000 for cancer research. This contribution, made in memory of Mdm Chee, will go towards supporting research projects that will help shape the next generation of innovative cancer research. We […]

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Jan 05, 2022 C K Sangamitha 0 comments
Immunohistochemistry Study of Tumor Vascular Normalization and Anti-Angiogenic Effects of Sunitinib Versus Bevacizumab Prior to Dose-Dense Doxorubicin/Cyclophosphamide Chemotherapy in HER2-Negative Breast Cancer. (Breast Cancer Res Treat, Dec 2021)

December 24, 2021

Tumor angiogenesis controlled predominantly by vascular endothelial growth factor and its receptor (VEGF-VEGFR) interaction plays a key role in the growth and propagation of cancer cells. However, the newly formed network of blood vessels is disorganized and leaky.

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Dec 24, 2021 Celine Tam 0 comments
Super enhancer-mediated upregulation of HJURP promotes growth and survival of t(4;14)-positive multiple myeloma (Cancer Res, Dec 2021)

December 24, 2021

Multiple myeloma (MM) is an incurable malignancy with marked clinical and genetic heterogeneity. The cytogenetic abnormality t(4;14) (p16.3;q32.3) confers aggressive behavior in MM. Recently, essential oncogenic drivers in a wide range of cancers have been shown to be controlled by super-enhancers (SE).

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Dec 24, 2021 Celine Tam 0 comments