With continuing advances in high-throughput sequencing technologies, the amount of genomic and epigenetic data is increasing exponentially, giving us a great opportunity to boost our understandings of complex biological systems.
Genomic rearrangements, also known as structural variations (SVs), are large scale alterations that changes the DNA structure. They include deletions, duplications, insertions, and other forms that are accompanied by copy number changes as well as inversions, translocations, and other copy-neutral forms. They are an important type of variation, affecting an order of magnitude more base pairs than single nucleotide variations (SNVs) in normal human population. In cancer, several chromosomal translocations have been identified and subsequently became targets of successful treatments. However, the functional impact of genomic rearrangements and their roles in treatment response are largely unexplored. We are developing new computational methods and exploring large scale cancer omics data to infer the mutational mechanisms leading to these alterations, to identify potential disease-driving events, and to study how they affect treatments.
We are also interested in the evolutionary process of cancer. Cancer cells often harbor tens of thousands of genetic alterations in various forms that are accumulated over a long period of time. Not all cells have the same alterations since alterations may occur during each cell division. These cells cooperate with each other and compete with each other, as well as with the normal cells surrounding them. We are developing methods to dissect the clonal and subclonal structures of solid tumors and to investigate how they evolve over time.