2019

11th Hope Meeting with Nobel Laureates Inspires CSI PhD Student

March 7, 2019

Organized by the Japan Society for the Promotion of Science (JSPS), the 11th Hope Meeting with Nobel Laureates was held in Okinawa, Japan from 4-8 March 2019. Shreya Kar, Presidents’ Scholar PhD student from Dr. Alan Prem Kumar’s group, was privileged to be selected to attend this meeting.At the Hope Meetings each year, outstanding graduate students are selected from countries and areas in the Asia-Pacific and Africa to converge for a time of dynamic discussions and the opportunity to learn from a lineup of distinguished Nobel Laureates. The annual symposium aims to foster the next generation of researchers and enhance their research capabilities.

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Mar 07, 2019 Karol Chia 0 comments
CSI Research Fellow Nominated to Attend Global Young Scientists’ Summit

February 27, 2019

Congratulations to Dr Xianning Lai, a research fellow in Dr Alan Prem Kumar’s group for being successfully nominated to attend the Global Young Scientists’ Summit (GYSS) @one-north from 20 to 25 January. She was one of the highly motivated and passionate PhD students and postdoctoral associates under 35 chosen from all over the world to […]

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Feb 27, 2019 Karol Chia 0 comments
2018 Year in Review: Research Highlights

February 26, 2019

From identifying candidate targets for treatments of Glioblastoma (GBM) to developing a computational platform to facilitate drug combination design, 2018 has been an exciting year for the cancer research field. Here is a look back on some of our research highlights in 2018:

1. ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis.

Image result for T-cell leukemogenesisThe research team led by Dr Takaomi Sanda found a new interaction in the cell that leads to the development of T-cell leukemia.The group discovered that the TAL1 complex directly acts on AT-rich interactive domain 5B (ARID5B) and positively regulates the ARID5B gene in T-cell acute lymphoblastic leukemia (T-ALL) cells. Results from the study reveal an oncogenic function for ARID5B and indicate that the ARID5B overexpression supports the survival of TAL 1-positive T-ALL cells. Their insightful findings have elucidated the role of ARID5B as a critical transcriptional regulator controlled by TAL 1 in T-ALL.

Genes & Development, 2018

2. Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer.

Image result for non-small cell lung cancerIn a study on Non-Small Cell Lung Cancer (NSCLC), Dr Azhar Ali and his team found a new signalling pathway in cells that involves fatty acid molecules. Fatty Acid Synthase (FASN) mediates Epidermal Growth Factor Receptor (EGFR) palmitoylation and supports tumour growth in EGFR mutated NSCLC. The inhibition of FASN hinders tumour growth in both the cell culture systems and in vivo models. By testing an anti-obesity drug, Oristat, the group identified FASN as a candidate target for future therapeutic treatments.

EMBO Molecular Medicine, 2018

3. The basic helix-loop-helix transcription factor SHARP1 is an oncogenic driver in MLL-AF6 acute myelogenous leukemia.

Image result for acute myelogenous leukemia.An exciting study led by Prof Daniel G. Tenen identified SHARP1 as a novel oncogenic target in MLL-AF6 AML Results showed an overexpression of SHARP1 in MLL-AF6 AML patients. Through a series of knockdown experiments, the team concluded that SHARP1 plays a critical role in maintaining clonogenic growth and preventing apoptosis in MLL-AF6 AML cells. This study provided important insights for understanding the role of SHARP1 to define targeted therapeutic modality for AML patients.

Nature Communications, 2018

4. Targetable BET proteins- and E2F1-dependent transcriptional program maintains the malignancy of glioblastoma.

Image result for glioblastomaIn the most common primary adult brain tumour, Glioblastoma (GBM), GBM cells develop insensitiveness to BET bromodomain inhibitors (BBIs) yet develop persistent reliance on BET protein. Prof H. Phillip Koeffler’s team used a next-generation chemical degrader of BET proteins (dBET6) and induced a targeted degradation of BET proteins in GBM. The group demonstrated that the dBET6 induces efficient degradation of BET proteins and represses the proliferation, self-renewal, and tumourigenic ability of GBM cells. Results from this research reveals crucial functions of BET proteins and indicates that targeted degradation of BET proteins in GBM has therapeutic merits.

Proceedings of the National Academy of Sciences of the United States of America, 2018

5. Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer.

Image result for DEAH box helicase 9The research team led by Dr. Polly Chen elucidated the regulatory role of DHX9 as a bidirectional regulator in A-to-I editing. Results from the study suggest that DHX9 catalyzes active remodelling of the ADAR substrates into distinct structural signatures, exerting opposing regulatory effects which are dependent on the ADAR1 specificity of editing sites. Most importantly, the team demonstrated the functional importance of DHX9 in tumourigenicity, which will contribute to a better understanding of A-to-I editing.

Nucleic Acids Research, 2018

6. Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide.

Image result for liver cancerFFW, a peptide drug has been found to be effective in disrupting the activity of SALL4 – a protein related to tumour growth in Hepatocellular Carcinoma(HCC), or primary liver cancer. Developed by Prof Daniel G Tenen’s group; results from their study suggest that FFW inhibits the transcription-repressor function of SALL4 and causes a significant up-regulation of transcripts that are favourable to patient survival. By identifying the SALL4-NuRD complex as a drug target and FFW as a viable drug candidate, results from this study could pave the way for the treatment of HCC.

Proceedings of the National Academy of Sciences of the United States of America, 2018

7. TIP60 represses activation of endogenous retroviral elements.

Image result for endogenous retroviral elementsIn many cancer types, primarily in breast and colorectal cancers, TIP60 (a lysine acetyltransferase) has been observed to be downregulated. In this study, Dr Sudhakar Jha’s team explored the role of TIP60 in tumour progression regulation and demonstrated that TIP60 is responsible for the silencing of endogenous retroviral elements (ERVs). The group identified a unique mechanism of ERV regulation in cancer cells mediated by TIP60 and BRD4 through the regulation of histone H3 K9 trimethylation, and a new tumour suppressive role of TIP60 in vivo.

Nucleic Acids Research, 2018

8. Optimizing drug combinations against multiple myeloma using a quadratic phenotypic optimization platform (QPOP).

Image result for Optimizing drug combinations against multiple myeloma using a quadratic phenotypic optimization platform (QPOP).In a multidisciplinary research team led by Dr Edward Chow, the group developed a computational platform, the Quadratic Phenotypic Optimisation Platform (QPOP), which aims to facilitate drug combination design and identify the most effective combinations for individual patients. Using quadratic surfaces, QPOP models the biological effects of drug combinations to identify effective drug combinations. The team applied QPOP to bortezomib-resistant multiple myeloma cell lines and identified the drug combinations for the most optimal treatment of multiple myeloma. Their landmark innovation could be a potential avenue for the treatment of multiple myeloma.

Science Translational Medicine, 2018

9. Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression.

Image result for squamous cell carcinomasProf H. Phillip Koeffler’s team carried out epigenomic profiling of squamous cell carcinomas (SCCs) and found a molecular pathway that promotes tumor growth in SCC. The group provided a comprehensive overview of transcription dysregulation in cancer biology mediated by master transcription factors and super-enhancers. With no effective targeted regimens being established for SCC, these new findings establish a new possibility for its treatment.

Nature Communications
, 2018

10. Aberrant hyper editing of myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis.

Recent research has shown that RNA abnormalities are associated with different cancers such as gastric cancer and liver cancer. In this study, Prof Chng Wee Joo and his team established an association between RNA abnormalities and Multiple Myeloma (MM) development. The abnormally modified state of MM RNA has been found to be responsible for the overexpression of ADAR1, an RNA-editing enzyme as well as the irregular RNA editing of NEIL1, a gene associated with lung carcinoma and colorectal cancer. Their novel findings unraveled novel insights into multiple myeloma molecular pathogenesis at the global RNA level, allowing the development of novel treatment options for MM patients.

Blood, 2018

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