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Bek Chai Heah Laboratory of Cancer Genomics

​Research head:​Professor Kam Man HUI
​Research team:

Hongping XIA
Amudha DEIVASIGAMANI
Muthukumar RAJASEKARAN
Clara Kai Ting KOH

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and presents a great public health and social burden. HCC is an epithelial cancer originating from hepatocytes and has been postulated to result from a series of genetic alterations attributable to a diverse range of causes. HCC is a highly therapyresistant cancer. Surgical treatments, including hepatic resection and orthotopic liver transplantation, provide the best option for cure in selected patients; yet, the long-term, disease-free survival rate remains unsatisfactory. Tumour recurrence and metastases are the major complications in more than two-thirds of these patients, with a poor prognosis and no proven effective survival-prolonging treatment modality available. There is indeed a great unmet need for new effective therapies for HCC. To tackle HCC, our laboratory employs unbiased, genome-wide strategies to identify key genes/regulatory pathways that are altered in relevant human HCC tissues. Further, we seek to understand how these changes affect the carcinogenesis of HCC, with the aim to modulate these regulatory pathways against the disease. We have systematically gathered molecular evidence and, through clinical corroboration of the data, have discovered molecular biomarkers that can provide clinically meaningful avenues for designing strategies independently from clinical risk factors. This, in turn, can be used to decipher the underlying molecular networks leading to HCC recurrence and identify reliable diagnostic and prognostic molecular biomarkers to develop novel therapeutics for HCC (Figure 1).

Selected publications:

1. Hypoxia-induced modulation of glucose transporter expression impacts 18F-fluorodeoxyglucose PET-CT imaging in hepatocellular carcinoma. Xia H, Chen J, Gao H, Kong SN, Deivasigamani A, Shi M, Xie T, Hui KM. Eur J Nucl Med Mol Imaging. 2020; 47:787-797.
2. Genome-wide CRISPR knockout screens identify NCAPG as an essential oncogene for hepatocellular carcinoma tumor growth. Yu Wang, Bin Gao, Peng Yang Tan, Yohana Ayupriyanti Handoko, Karthik Sekar, Amudha Deivasigamani, Veerabrahma Pratap Seshachalam, Han-Yue OuYang, Ming Shi, Chan Xie, Brian Kim Poh Goh, London Lucien Ooi, and Kam Man Hui. FASEB J. 2019; 33:8759-8770.
3. Clinical and metabolomics analysis of hepatocellular carcinoma patients with diabetes mellitus. Xia H, Chen J, Sekar K, Shi M, Xie T, Hui KM. Metabolomics. 2019; 15(12):156.
4. CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling. Chen J, Rajasekaran M, Xia H, Kong SN, Deivasigamani A, Sekar K, Gao H, Swa HL, Gunaratne J, Ooi LL, Xie T, Hong W, Hui KM. EMBO J. 2018; 37(20); e99395.
5. Nguyen AT, Chia J, Ros M, et al. Organelle-specific O-glycosylation drives MMP14 activation, tumor growth, and metastasis. Cancer Cell. 2017;32:639–653.e6.
6. Chen J, Rajasekaran M, Xia H, et al. The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/β-catenin signalling pathway. Gut. 2016; 65:1522–1534.
7. Xia H, Li F, Hu X, et al. pH-Sensitive Pt nanocluster assembly overcomes cisplatin resistance and heterogeneous stemness of hepatocellular carcinoma. ACS Central Sci. 2016; 2:802–811.
8. Xia H, Kong SN, Chen J, et al. MELK is an oncogenic kinase essential for early hepatocellular carcinoma recurrence. Cancer Lett. 2016; 383:85–93.

Lab Unit of Paediatric Brain Tumour Research Office

​Research head:​Asst Professor Wan-Yee TEO (Recipient of National Medical Research Council Transition Award and National Medical Research Council Clinician Scientist Award)
​Research team:

Shiying Huang
JieLing Pan
Huixin Lau
Jung Yi ONG
Joshua WEE Aik Liang

The laboratory unit for the Paediatric Brain Tumour Research Office (PBTRO), SingHealth Duke-NUS Academic Medical Centre was established in 2015, with competitive grants secured. We are a dynamic laboratory unit and have steadily expanded our team and international collaborations over the past few years. Our goal in research is to derive findings that enable a reflective change in the practice of medicine in brain tumours. Our team (PBTRO) shares a common dream to present globally competitive research findings in the field of neurooncology, addressing these areas in the practice of medicine through science. We work on several types of brain tumours, both in paediatric and adult populations. One major research focus of our group is in the brain tumour microenvironment, translating research findings in tumour biology and genomics to bedside benefits for patients with brain tumours. Our research combines genomic methodologies and mouse models to study the complex regulation and developmental biology of brain tumours. We place a large emphasis on the preclinical development of therapeutics for brain tumours that currently have no cures, drawing from various strengths in genomics, high throughput functional assays optimised in our laboratory, and a large, unique cohort of patient-derived orthotopic mouse models of brain tumours developed for preclinical testing.

EXCERPT FROM PBTRO TEAM MEMBERS & INTERN STUDENTS

“Our work focuses on cell culture and utilises molecular techniques to unravel the cell biology behind the drug effects on brain tumours; this is in line with our team goal to discover effective and novel treatments for the benefit of patients.”

“The most important insight I learnt from this internship was realising the tenacity of character required to become a successful researcher. Their passion for their work, and their grit and perseverance constantly inspire me to work hard in my studies knowing that my study now is not as challenging as the lives of these researchers.”

Our Work at Laboratory 609-T, Laboratory Unit of Pediatric Brain Tumour Research Office, SingHealth Duke-NUS Academic Medical Centre

Selected publications:

1. Teo WY, Elghetany MT, Liu D, et al. Therapeutic implications of CD1d expression and tumor infiltrating macrophages in pediatric medulloblastomas. J Neurooncol. 2014;120:293–301. *
2. Teo WY, Ross J, Bollo RJ, et al. Atypical location and clinical behavior of nonteratomatous intracranial germ cell tumors in children. J Neurosurg Pediatr. 2014;25:1–8. * (Podcast highlight by the journal)
3. Teo WY, JMF Su, Shen JS, et al. Implications of tumor locations on subtypes of medulloblastoma (Priority Report with Commentary Highlight). Pediatr Blood Cancer. 2013;60:1408–1410.
4. Teo WY, Sekar K, Seshachalam P, Shen J, Chow WY, Lau CC, Yang H, Park J, Kang SG, Li X, Nam DH, Hui KM. Relevance of a TCGA-derived Glioblastoma Subtype Gene-Classifier among Patient Populations. Sci Rep. 2019 May 15;9(1):7442.* Top 100 Most Downloaded Cancer Articles in Scientific Reports in 2019. Metrics: Article downloaded 2031 times (19 March 2020)
5. Qi L, Kogiso M, Du Y, Zhang H, Braun FK, Huang Y, Teo WY, Lindsay H, Zhao S, Baxter P, Zhao X, Yu L, Liu Z, Zhang X, Su JM, Adesina A, Yang J, Chintagumpala M, Perlaky L, Tsz-Kwong Man C, Lau CC, Li XN. Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors. Cancer Lett. 2020 Sep 3:S0304-3835(20)30449-3. doi: 10.1016/j.canlet.2020.08.035. Online ahead of print
6. Teo WY. Implications for border containment strategies when COVID-19 presents atypically. Public Health. 2020 Jul 24;186:193-196. doi: 10.1016/j.puhe.2020.07.019.*


*Denotes publications where Teo WY is a corresponding author