My research interests are focused on the molecular genetics and genomics of gastric and colorectal cancers. We have performed genomics studies on large series of gastric and colorectal cancers using next-generation sequencing, expression microarray and DNA SNP chip. Our study revealed the genomic landscape of gastric cancer and first identified frequent mutation of ARID1A, a chromatic remodeling gene, in gastric cancer. Our study of gene expression have revealed novel modules reflecting intrinsic properties of tumour and normal cells, tumour-stroma interaction, host immune response and pathways of stem cell regulation. This information have led to the identification of new tumour suppressor genes frequently silenced in gastrointestinal cancers, genes that can modify tumour aggressive behaviour and patient outcome, and genes that contribute to maintenance of stem cell niche.

Our team has extensively characterized the genetic basis for the exceptionally high incidence of early-onset colorectal cancer (CRC) in Hong Kong. We have uncovered the mutation spectrum of germline DNA mismatch repair gene, and revealed a founder mutation that is common in the Southern Chinese population which originated between 22 and 103 generations ago. We have described the first example of heritable germline methylation of MSH2 gene promoter as a cause of hereditary colon cancer, and uncovered a novel mechanism of methylation induction and gene silencing through abrogation of transcriptional termination signal in an upstream neighbouring gene named EPCAM (TACSTD1). These findings have resulted in incorporation of EPCAM deletion into the standard genetic diagnosis protocol for Lynch Syndrome worldwide. Our laboratory is now applying the research findings to patient care, by providing a charitable genetic diagnosis service including genetic testing and referral for prophylactic screening for early-onset or familial colorectal cancer patients and their families. We have also studied in depth the role of the BRAF mutation in colorectal cancers, and discovered an interesting relationship between the BRAF mutation and various pathways of colorectal carcinogenesis.

The long term goal of our laboratory is to utilise genomics technology to identify novel pathways of carcinogenesis and hereditary predisposition for colorectal and gastric cancers, and to identify biomarkers for early detection, patient stratification, prognostication or drug targets.