IGSP Faculty

Patrick, Tan, MD, PhD

Associate Research Professor

We thought that since the tumors were spending costly cellular resources and energy to control the expression of these particular genes, they must have functional importance in cancer.

Dr. Patrick Tan, MD, PhD is an associate professor of Duke-NUS Graduate Medical School in Singapore. He received his B.A. from Harvard University in 1992, and attended Stanford University School of Medicine from 1992-2000 where he received his MD PhD degree. Dr. Tan is also a Group Leader at the Genome Institute of Singapore, and in 2008 was appointed a Program Leader in Genomic Oncology at the Cancer Sciences Institute of Singapore.

Other positions include being a Principal Investigator (Adjunct) at the National Cancer Centre of Singapore, and a Senior Research Fellow (Adjunct) at Defence Medical and Environmental Research Institute, Defence Science Organization (DMERI@DSO), Singapore. All of these positions have been held since 2004. Dr. Tan is also a member of Bioethics Advisory Committee (BAC) to the Government of Singapore.

Research Statement

Our group focuses on the application of genome and proteome-level targeted technologies to address biological questions in cancer and infectious disease. Although these two scientific domains may appear quite separate, a number of common cancers are have been shown to possess infectious etiologies, including hepatitis viruses in hepatocellular carcinoma, and Helicobacter pylori in gastric cancer. We are also intrigued by the rapid mutability and genomic plasticity of the cancer genome, as such features are frequently observed in pathogens as well. Thus, we believe that insights and principles from one domain are likely to shed light on problems encountered in the other. Our specific ongoing projects include:

1) Genomic and Proteomic Discovery of Biomarkers in Breast Cancer

Breast cancer is the most common malignancy for females in Singapore. In comparison to the US and Europe, breast cancers in Asia tend to present in women at an earlier age. The current reason for this epidemiological difference is not known. A central challenge in the current management of breast cancer lies in the selection of appropriate treatment regimens for individual breast cancer patients, so as to maximize therapeutic benefit while minimizing adverse drug-related outcomes. Our breast cancer program focuses on the identification of molecular biomarkers, such as genetic variants, expression signatures, and proteomic patterns, which could aid an oncologist in providing personalized treatment options to individual breast cancer patients. For breast cancer, we have used DNA microarrays to establish a genomic database comprising hundreds of Asian breast cancer samples, and used this information to identify several expression signatures that can accurately predict various clinical parameters (eg normal vs malignant, estrogen receptor status, response to tamoxifen) associated with an unknown breast sample. To evaluate the efficacy of these signatures in a busy clinical setting, we are currently conducting a prospective trial using customized microarrays carrying these signatures in patients treated at the National Cancer Centre of Singapore.

2) Discovery of oncogenic pathways and processes in gastric cancer.

Gastric cancer is the second leading cause of global cancer mortality. Despite this, 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. Using a combination of array-based comparative genomic hybridization and expression profiling strategies, we have shown that gastric cancers can be subdivided into distinct molecular subtypes which distinct clinical outcomes. To achieve a better understanding of gastric cancer at the levels of systems topology, functional modules, and constituent genes, we have formed an international Gastric Cancer Consortium comprising members from Australia, Hong Kong, Japan, and Singapore, to pool expression data from >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 signaling through this receptor may contribute to gastric carcinogenesis. We are currently extending these studies to larger cohorts of gastric cancers to further investigate this possibility.

3) Host-pathogen Interactions in Burkholderia pseudomallei (in collaboration with the Genome Institute of Singapore).

The Gram-negative microbe Burkholderia pseudomallei (Bp) is a tropical pathogen and potential biowarfare agent, being the causative agent of the often-fatal human disease melioidosis. The molecular mechanisms regulating Bp biology and virulence are poorly understood. We are undertaking a research programme designed to systematically generate, characterize, and integrate comprehensive genomic and transcriptional information for this bacterium, and to interpret this molecular information in the context of specific microbial phenotypes and the factors modulating the host-pathogen encounter. Using microarrays and proteomics, we have described the patterns of molecular variation in various Burkholderia species, and the extent of genomic, transcriptional, and proteomic variability in different isolates of Bp. We have also used the transcriptional alterations exhibited by Bp during growth to identify novel virulence factors used by Bp to cause meliodosis. We are currently using C. elegans as a host model to identify potential genetic factors in hosts that can provide enhanced susceptibility or resistance to infection.

Recent Publications