Discovering novel drivers and pathways in CLL. Leveraging the availability of NGS technologies, Dr. Wang has identified and assessed the potential functional effects of genetic mutations within CLL cells (Wang L et al NEJM 2011, editorial commentary). This initial work was extended from 91 to 160 CLL samples (Landau D et al Cell 2013), leading to increased sensitivity in detecting novel CLL-associated genes and pathways. Recently, she discovered novel private driver mutations with integrated DNA and RNA level single-cell approaches and confirmed the prevalence of convergent evolution in CLL (Wang L et al Genome Res 2017).
Defining the impact of non-recurrent mutations on CLL biolog. Utilizing innovative nano-scale delivery methods, Dr. Wang demonstrated that Wnt pathway mutations affect CLL tumor cell survival and contribute to CLL pathogenesis (Wang et al Blood 2014, cover image). This led to the discussion about how non-recurrent somatic mutations could impact cancer biology (Wang et al Blood 2014, editorial commentary).
Dissecting RNA splicing factor mutations in CLL. One of the surprising findings from the cancer genome sequencing of CLL is the discovery of high frequency mutations in the RNA splicing factor SF3B1. The presence of these mutations is associated with fast disease progression, an overall poor survival rate, and chemotherapy refractoriness in CLL patients. With an integrated RNA-sequencing and functional interrogation approach using primary CLL cells and cell lines, Dr. Wang demonstrated how these splicing factor mutations impact RNA splicing and resulted in functional changes on multiple CLL-associated pathways (Wang L et al Cancer Cell 2016, cover image).