News

Congratulation to Associate Professor Gautam Sethi from the Department of Pharmacology at the Yong Loo Lin School of Medicine, who led a team of international researchers, at the National University of Singapore (NUS), has found that nimbolide, a bioactive terpenoid compound derived from Azadirachta indica or more commonly known as the neem plant, could reduce the size of prostate tumour by up to 70 per cent and suppress its spread or metastasis by half.

• NUS News
• Channel NewsAsia, 28 September 2016
• Vasantham News, 28 September 2016
• Oli 96.8FM, 28 September 2016
• Tamil Murasu, 29 September 2016, p9
• Lianhe Zaobao, 15 October 2016, p13

Congratulation to Ms Cai Wanpei, PhD student of Dr Alan Prem Kumar, for receiving an EMBO Travel Grant (€500) based on her abstract to present her work at the annual international Wnt Meeting in Brno, Czech Republic 14-17 September 2016. She’s the only one in Singapore who got this Travel Grant.

Congratulation to Ms Wang Chao, PhD student of Dr Alan Prem Kumar, for winning of the McDonnell International Scholars Academy 6th International Symposium in Brisbane, Australia (22-25 Sept 2016) – People’s Choice Award for the Population Aging and Global Health 3MT competition.

The MV Arunachalam Oration is organised annually to provide public education and to raise awareness on complex neurological disease and disability. The program is curated by Dr. Ennapadam S. Krishnamoorthy, Neuropsychiatrist and supported by the Vellayan Chettiar Trust represented by Mr. A Vellayan, Trustee, Director of Murugappa Group and son of Shri. MV Arunachalam.

Hydrogen sulphide, a gas known for its rotten egg smell, may be able to help men improve the quality of their sperm and thus their fertility, if an NUS study on animals is translatable to humans. Published in the journal Nitric Oxide, the new findings can potentially give rise to new approaches in treating male infertility.

In experiments conducted on mice, researchers from the Yong Loo Lin School of Medicine discovered that hydrogen sulphide protected the male spermatozoa from heat-related damage which can result in infertility. The work was co-led by Professor P C Wong from the Department of Obstetrics and Gynaecology and Associate Professor Bian Jinsong from the Department of Pharmacology.

The stinky gas, which is produced naturally in small quantities by the body, protects the heart, brain, and cells due to its antioxidant effect, said Assoc Prof Bian. When facing oxidative stress — a situation when the body is overwhelmed by harmful free radicals — cells can be damaged or even killed.

Hydrogen sulphide can produce antioxidative effect to counter oxidative stress, but its efficacy decreases with falling levels. The team’s animal model study showed that heat reduced levels of the gas, leading to lower sperm activity. If sufficient gas is provided to balance the internal deficiency in the body, the level can be corrected, Assoc Prof Bian explained. However, determining the right concentration of the gas is a challenge, he admitted, and further tests will be needed.

Hydrogen sulphide is widely studied for its antioxidative properties, but the NUS investigation represents the first on male reproductive cells.

Prof Wong pointed out that sperm can be affected by factors such as ageing, smoking, drugs, alcohol, heat, stress, toxins, infection and others. Current treatments for male infertility include oral drugs, male hormone products and injections, but they do not succeed in all patients.

Although their findings are exciting, Prof Wong underscored that many steps are required to ensure the same experiments work for humans, before figuring out how to administer the gas. “We hope this can transform into something we can treat people with,” he said, but cautioned that “we must not jump the gun”.

Read the press release and media article.

Congratulation to Associate Professor Christopher Chen, first person on the right, winning the Faculty Research Excellence Award 2016. The Faculty Research Award recognizes staff members for their continued excellence and leadership in research.

Congratulation to Peh Hong Yong, PhD student of A/P Wong Wai-Shiu Fred, for winning the Best Oral Presentation Award.

Congratulation to the following PhD students for winning the Best Poster Presentation Award:

1. Chan Tze Khee, student of A/P Wong Wai-Shiu Fred
2. Dong Jinrui, student of A/P Wong Wai-Shiu Fred
3. Malavika Srikanth, student of Dr Deron Raymond Herr
4. Wang Chao, student of Dr Alan Prem Kumar

The Department of Pharmacology is proud to have Ms Wang Chao, a PhD student in Dr Alan Prem Kumar’s group, selected to participate in the 8th HOPE Meeting to be held in Japan in March 2016. She will be joining 74 other carefully selected Asian-Pacific and African participants to attend this meeting.

Since 2008, the Japan Society for the Promotion of Science has been organizing HOPE Meetings annually with an aim of advancing science and technology within the Asia-Pacific and Africa region. The title “HOPE” signifies the promise held for young scientists and optimism for a bright science and technology future in the Asia-Pacific and Africa region. It provides opportunities for excellent doctoral students and young researchers to engage in interdisciplinary discussions with Nobel laureates and other distinguished scientists.

Congratulations to Ms Cai Wanpei, a PhD student from Dr Alan Prem Kumar’s group for receiving the prestigious Avon-AACR International Scholar-in-Training Travel Award in the amount USD$2,000 to attend and present her PhD work at the above conference. Her abstract was chosen for this award because the work is highly rated by the Abstract Selection Committee.

DEAD-box RNA helicase DP103 as a Novel Regulator of Wnt/β-catenin Signaling Pathway and Promotes Cancer Stem Cell-like Behavior in Triple Negative Breast Cancers

Wanpei Cai^1,2, Jit Kong Cheong⁵, Edison⁵, Arindam Banerjee^1,8, Tuan Zea Tan¹, Einas M. Yousef⁹, Louis Gaboury⁹, Jean Paul Thiery^1,3, Peter E. Lobie1,², David M. Virshup^3,5, Celestial T. Yap⁴, Alan Prem Kumar^1,2,6,7

¹Cancer Science Institute of Singapore, National University of Singapore; Departments of ²Pharmacology and ³Biochemistry, ⁴Physiology Yong Loo Lin School of Medicine, National University of Singapore; ⁵Cancer & Stem Cell Biology Program, Graduate Medical School, Duke-NUS; ⁶School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Western Australia; ⁷Department of Biological Sciences, University of North Texas, Denton, TX, USA; ⁸Somers Cancer Research Building, Cancer Research UK Centre, Faculty of Medicine, University of Southampton; ⁹Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal

Despite recent advances in breast cancer therapeutics, mortality of metastatic triple negative breast cancer (TNBC) subtype remains high; due to their lack of hormone receptors expression for targeted therapy. Aberrant activation of Wnt/β-catenin signaling has been associated with breast cancers; where 40% of total breast cancers have elevated β-catenin levels with increased Wnt activity. Recently, we identified DEAD-box RNA helicase DP103 as a novel prognostic biomarker and metastasis-driving oncogene; highly expressed in TNBC subtype. Interestingly, we found high DP103 expression to be positively correlated with high β-catenin expression in clinical specimens (n=400). This led us to hypothesize a possible role of DP103 in modulating the Wnt/β-catenin pathway in TNBCs. Depletion of DP103 in metastatic TNBC cells decreases Wnt/β-catenin activity and expression of downstream Wnt target genes, while overexpression of DP103 increases Wnt activity. Depletion of DP103 also decreases phosphorylation of LRP6 and several important Wnt modulators required for downstream Wnt activation. Moreover, induction of Wnt/β-catenin signaling in Wnt responsive TNBC cells also significantly increased DP103 expression, indicating a possible positive feedback loop. Both canonical and non-canonical Wnt signaling is known to independently promote stem cell growth in mammospheres. Herein, we will also provide evidence on the role of DP103 in promoting breast cancer stem cell-like properties. Collectively, our data show a novel regulatory role of DP103 in the Wnt/β-catenin signaling pathway and in promoting breast cancer stem cell-like behavior, presenting itself as a potential drug target in TNBC patients.

The Asian Society Against Dementia Conference was held in Colombo Sri Lanka from 14th-16th November, 2014. Dr. Summer Xin Xu was selected to present on “The utility of the Mini-Mental State Examination in identifying dementia and non-demented cases in a memory clinic in Singapore” in the research forum free paper poster presentation and won the best poster presenter prize from her work which is part of the Memory Aging and Cognition Centre’s (MACC) at Department of Pharmacology and National University Health System (NUHS) research programme.