Research

Our laboratory is interested in the genetics of cancer and in particular, how genetic alterations affecting processes such as RNA splicing drive cancer and expose potential therapeutic vulnerabilities.

Alternative splicing is an essential mode of gene regulation that greatly diversifies the coding potential of the transcriptome. However, this process is often dysregulated in human cancer. Recent large-scale genomic surveys of multiple cancer types have also identified somatic alterations in splicing factors and other RNA-binding proteins, demonstrating that global changes in RNA processing can play a significant role in tumorigenesis. Despite our ability to comprehensively detect the landscape of alternatively spliced transcripts through next-generation sequencing, it has remained difficult to predict much of the functional impact of aberrant splicing.

Our group aims to decipher how patterns of alternative splicing control cellular processes, and when perturbed, can lead to pathogenic states such as cancer. We are particularly interested in characterizing RNA-binding proteins known to be mutated in cancer and their functional role in alternative splicing and other steps in RNA processing. We are also interested in understanding how the expression of specific isoforms may regulate fundamental processes such as cell division and cell death. To tackle these questions, we make extensive use of genome editing, high-throughput screening and a variety of genomic approaches.