Heartiest congratulations to 5 of our PhD students on their achievements at the annual Graduate Scientific Congress 2014! Held on 11 March 2014 and organised by the Yong Loo Lin School of Medicine, the congress offers graduate students a fantastic opportunity to exhibit their exciting research to nearly 400 participants comprising of fellow peers, academic staff and related companies.
Best Poster Presentation
Desmond Chin (PI: A/Prof Motomi Osato)
Title: Cbfb deficiency results in differentiation blocks and stem cell/progenitor expansion in hematopoiesis.
Lau Wai Hoe (PI: Prof Peter Lobie)
Title: Trefoil factor 3 promotes angiogenesis in mammary carcinoma
Mammary carcinoma (MC) cells produce various growth factors that stimulate endothelial cells to promote angiogenesis in MC. Among these growth factors, Trefoil Factor 3 (TFF3) is a small secreted protein which is involved in mucosal protection and repair of gastrointestinal tract. Our laboratory has previously identified TFF3 as an orthotopically expressed oncogene in MC. However, the potential functional role of TFF3 in MC angiogenesis has not been determined. Herein, we demonstrated that TFF3 secreted from MC cells promoted human umbilical vein endothelial cells (HUVEC) monolayer cell cycle progression and proliferation, survival, migration, invasion, and in vitro tubule formation. Hence, TFF3 is a promoter of tumor angiogenesis, which may co-coordinate with the growth promoting and metastatic actions of TFF3 in MC to enhance tumor progression.
Best Research Publication Award
Xu Liang (PI: Prof Phillip Koeffler)
Title: Genomic and functional characterizations of phosphodiesterase subtype 4D in human cancer.
Phosphodiesterase subtype 4D (PDE4D) gene was homozygously deleted in 198 cases of 5,569 primary solid tumors, with most being internal microdeletions. Unexpectedly, the microdeletions did not result in loss of their gene products. IHC staining revealed that its protein levels were up-regulated in primary tumors. Importantly, depletion of endogenous PDE4D caused apoptosis and growth inhibition of cancer cells while ectopic expression of PDE4D isoform2, enhanced the cell proliferation. Moreover, treatment of cancer cells with PDE4D inhibitor, 26B, triggered massive cell death and growth retardation. Our results suggest that although targeted by genomic homozygous microdeletions, PDE4D functions as a tumor-promoting factor and represents a unique targetable enzyme of cancer cells.
Best International Graduate Research Publication and Oral Presentation Award-FY2013/2014
Phyllis Chong (PI: A/Prof Chng Wee Joo)
Jolene Ho (PI: Prof Lorenz Poellinger)
Title: Hypoxia mediates tumourigenesis epigenetically via the H3K9 methylation regulators G9a and Jmjd1a
Hypoxia promotes tumour progression but it remains unclear how It regulates long-term adaptation toward these processes. We reveal a striking downregulation of the hypoxia-inducible histone H3 lysine 9 (H3K9) demethylase Jmjd1a as a hallmark of clinical human germ cell-derived tumours. Jmjd1a plays a crucial role as a tumour suppressor in opposition to the oncogenic H3K9 methyltransferase G9a. Investigating the hypoxia-driven epigenetic regulation of tumourigenesis by G9a and Jmjd1a, we found that anti-angiogenic genes were epigenetically dysregulated during hypoxia, corresponding with changes in promoter H3K9 dimethylation and H3K4 trimethylation mediating transcriptional repression and activation respectively. Importantly, this led to opposing tumour phenotypes where loss of Jmjd1a resulted in increased tumour growth and loss of G9a produced smaller tumours. Pharmacological inhibition of G9a resulted in inhibition of tumour growth, offering a novel therapeutic strategy for germ cell-derived tumours. Thus, we demonstrate a novel mechanistic link where hypoxia-regulated epigenetic changes are instrumental for the control of tumour growth and suggest that the targeting of G9a in cancer cells may offer a potential avenue for therapeutic intervention.