Joint Appointments:
Associate Professor, Duke NUS Graduate Medical School
Group Leader, Genome Institute if Singapore
Program Leader (Genomic Oncology), Cancer Sciences Institute of Singapore
Research Staff
Heidi CHENG
Veena GOPALAKRISHNAN
Tatiana IVANOVA
Junhao KOO
Ming Hui LEE
Dianne POH
Qin LUO
Hue Kian OH
Chia Huey OOI
Angie L.K. TAN
Jiong TAO
Hannah Z.A. WANG
Jeanie WU
Yonghui WU
Shenli ZHANG
Zhijiang ZHANG
Yansong ZHU
Hermioni ZOURIDIS
Selected Publications
Chia Huey Ooi, Tatiana Ivanova, Jeanie Wu, Minghui Lee, Iain Beehuat Tan, Jiong Tao, Lindsay Ward, Jun Hao Koo, Veena Gopalakrishnan, Yansong Zhu, Lai Ling Cheng, Julian Lee, Sun Young Rha, Hyun Cheol Chung, Kumaresan Ganesan, Jimmy So, Khee Chee Soo, Dennis Lim, Weng Hoong Chan, Wai Keong Wong, David Bowtell, Khay Guan Yeoh, Heike Grabsch, Alex Boussioutas, and Patrick Tan (2009)
Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer. PLOS Genetics doi:10.1371/journal.pgen.100676.
Yu K, Ganesan K, Tan LK, Laban M, Wu J, Zhao XD, Li H, Zhu Y, Wei CL, Hooi SC, Miller L, Tan P
A Precisely Regulated Gene Expression Cassette Potently Modulates Metastasis and Survival in Multiple Solid Cancers.
PLoS Genet. (2008) 4(7): e1000129.
Hou Q, Wu YH, Grabsch H, Zhu Y, Leong SH, Ganesan K, Cross D, Tan LK, Tao J, Gopalakrishnan V, Tang BL, Kon OL, Tan P
Integrative Genomics Identifies RAB23 as an Invasive Mediator Gene in Diffuse Gastric Cancer.
Cancer Res. (2008) 68: 4623-4630.
Ganesan K, Ivanova T, Wu YH, Rajasegaran V, Wu J, Lee MH, Yu K, Rha SY, Chung HC, Ylstra B, Meijer G, Kon OL, Grabsch H, Tan P
Inhibition of Gastric Cancer Invasion and Metastas is by PLA2G2A, a Novel β-catenin/TCF Target Gene. Cancer Res. (2008) 68(11):4277-4286.
Aggarwal A, Guo DL, Hoshida Y, Yuen ST, Chu KM, So S, Boussioutas A, Chen X, Bowtell D, Aburatani H, Leung SY, Tan P
Topological and Functional Discovery in a Gene Co-expression Meta-Network of Gastric Cancer.
Cancer Res. (2006) 66, 232-241 (cited on journal cover).
Cancers between individual patients often display strikingly different types of clinical behaviour including disease aggressiveness and responsiveness to treatment. Many of these differences are currently not predictable using conventional techniques for cancer classification, such as light microscopy and immunohistochemistry. Our laboratory employs genome-profiling technologies to identify molecular features of tumours that will enable such predictive classification, and to ultimately provide personalised cancer care.
Research Focus
Our group focuses on the application of genome-scale technologies to address biological questions in cancer. We are also intrigued by the rapid mutability and genetic plasticity of the cancer genome and believe that developing whole genome cartographies of tumours will enable us to better understand the molecular basis of cancer and to identify cellular pathways and molecular nodes for intervention. A major disease focus for our group is gastric cancer, which is the second leading cause of global cancer mortality. Despite this clinical importance, relatively little is known about the specific oncogenic pathways that regulate different aspects of the gastric cancer phenotype. We hope to identify and understand these pathways and ultimately use this knowledge to define rational therapeutic strategies for gastric cancer patients.
For example, using a novel computational approach, we showed that gastric cancers can be subdivided into different subtypes with differing patterns of oncogenic pathway activity and clinical outcomes. To achieve a better understanding of gastric cancer at the levels of systems topology, functional modules, and constituent genes, we formed an international Gastric Cancer Consortium comprising members from Australia, Hong Kong, Japan and Singapore, to pool expression data from more than 300 human samples profiled at various histological stages of gastric tumorigenesis, ranging from normal gastric tissue, chronic gastritis, intestinal metaplasia, to overt carcinoma. Using this combined database, we were able to show a conserved interaction between PLA2G2A, a gene whose expression was previously correlated with patient prognosis, and the EphB2 receptor, raising the possibility that signalling through this receptor may contribute to gastric carcinogenesis. We further extended this work to show that PLA2G2A is a novel target of the Wnt signalling pathway that functions to inhibit gastric cancer metastatasis.
In addition to our focus on gastric cancer, we have also actively participated in numerous projects involving lung, liver, and breast cancers.
Figure 1: Systems-Map of Gastric Cancer – Each circle represents a collection of genes that are tightly co-regulated across more than 300 gastric tissues. For more details see Aggarwal et al., (2006).
