Bio
My research has made major contributions in the areas of bioinformatics, genomics, human genetics, and cancer genomics. My early career focused on developing bioinformatics for the then-new field of genomics. I played important roles in ground-breaking genomics studies, including: (i) mapping the locations of human genes, which in general were not known at that time, (Deloukas et al., 1998, Schuler et al., 1996), (ii) generation of infrastructure for sequencing the human genome in the form of tiling paths of bacterial artificial chromosomes (Hudson et al., 1995), and (iii) the first proof-of-concept showing that DNA microarrays could be used for massively parallel, genome-wide genotyping of single-nucleotide polymorphisms (the first "SNP chips", Wang et al., 1998). This laid the groundwork for two decades of microarray-based genome-wide association studies (GWAS). I also released the widely used Primer3 software and website for PCR primer design (Rozen and Skaletsky, 2000, Untergasser et al., 2012). Primer3 remains extremely useful, with > 12,900 Google Scholar citations for the initial publication, including > 8,500 citations since 2009. I continue to maintain Primer3 as an open source project, and it has been downloaded > 120,000 times since 2009. Furthermore, Primer3 was recently incorporated into the NCBI PRIMER-BLAST service (http://www.ncbi.nlm.nih.gov/tools/primer-blast/, Ye et al., 2012), enabling it to serve an even wider research community. After working on bioinformatics for genomics, I changed focus to the genetics and genomics of the human and mammalian Y chromosomes. My research centered on understanding the genomic details of genetic lesions in human Y chromosomes, the underlying mutational mechanisms, and the phenotypic and population-genetic consequences of these mutations. This research led to publications in Nature Genetics and Nature (Kuroda-Kawaguchi et al. 2001, Tilford et al., 2001; Skaletsky et al., 2003; Rozen et al., 2003) as well as two papers in Nature Genetics on which I was senior author (Repping et al., 2003, Repping et al., 2006), plus additional, highly cited articles on which I was senior author (Repping et al., 2002, 331 citations in Google Scholar; Repping et al., 2004, 159 citations in Google Scholar). Other work that I did during this period has continued to underpin high-profile publications in the American Journal of Human Genetics (Rozen et al., 2009; Rozen et al., 2013) and Nature (Bellott et al., 2010; Hughes et al., 2010; Hughes et al., 2012; Bellott et al., 2014; Soh et al., 2014).
Since moving to Duke-NUS in 2008, I have made contributions in cancer genomics, human genetics, and in founding and directing the Duke-NUS Centre for Computational Biology. My work in cancer genomics has involved bioinformatics for finding somatic mutations in tumors and inferring possible consequences. This work led to multiple papers, including three in Nature Genetics, on which I am corresponding author (Ong et al, 2012; Zang et al., 2012, Chan-On et al., 2013). This work also led to Singapore being named the lead country for biliary-tract cancers and T-cell and NK-cell lymphomas in the International Cancer Genome Consortium. My laboratory’s analysis of an additional 100 to 200 bile-duct cancer genomes and a similar number of lymphomas will make important contributions to our understanding of these tumors. Another area of particular interest is analysis of physical mutations signatures in tumors to identify likely carcinogenic exposures. In a recent study of the mutation signatures caused by a carcinogenic herbal remedy, my laboratory unexpectedly found evidence that it contributed to liver cancers, in which this carcinogen was not previously implicated (Poon et al., 2013; Poon et al., 2014). Based on this and my role in the International Cancer Genome Consortium (ICGC), I am now co-leader of the ICGC Pan-Cancer Analysis Working Group on Mutation Signatures. The goals of this working group are to computationally extract the signatures and estimate signature contributions to each of > 2,000 tumor genomes and > 10,000 tumor exomes and to determine an optimal set of mutation classes for a collection of genomes at this scale. The working group will search for the endogenous processes and exogenous exposures responsible for these signatures through correlation to mutations of cancer genes and to exogenous exposures, including smoking, alcohol, pathogens, and so forth. Importantly, we will estimate the proportion of driver mutations caused by each signature across many types of tumors, and we will classify cancers according to the mutation signatures in their genomes. Cancer classification is an additional important focus of my laboratory. We recently showed the existence of three robust subtypes of gastric adenocarcinomas, based on their global gene-expression profiles. This research was published in Gastroenterology (Lei et al., 2013) and was also featured in a journal editorial. My work in the genetics of autism spectrum disorders (ASD) identified possibly causal mutations in ~10 genes. I began collaborations with Hongyan WANG, Eyleen GOH and Shawn JE to experimentally determine the neurobiological functions of these genes, and in particular, to determine if the variants identified in ASD patients have phenotypes in in vivo or in vitro model systems. At Duke-NUS, I founded and now direct the Duke-NUS Centre for Computational Biology (CCB). CCB faculty work in three areas: research, collaboration, and education. CCB faculty carry out research that depends heavily on computational biology and bioinformatics and pursue methodological research in these fields. CCB faculty also collaborate broadly with Duke-NUS and SingHealth investigators. Finally, CCB faculty advance bioinformatics education, including supervision of PhD students, contributing to coursework for the Duke-NUS PhD Program, and one-to-one mentoring of faculty, postdoctoral fellows, research staff, and students. I recently recruited two additional outstanding tenure track faculty to CCB. One is an expert in systems genetics, i.e. integrating genetic data with high-throughput systems biology data to understand functional pathways in human genetics. The other is an expert in the quantitative modeling of biological processes at the cellular, tissue, and organ levels. Recruitment of these two faculty brings the total number of Duke-NUS Office-of-Research faculty in CCB to four; together, these faculty have published > 100 peer-reviewed papers since 2011.
Education
Doctor of Philosophy
New York University, United States
Master of Science
New York University, United States
Bachelor of Arts
University of California, Riverside, United States