Quantitative Translation of the Cancer Genome to Proteome

Monitoring and Manipulating the Genome to Drive Cancer Pathogenesis and Changes in Protein-level Abundance and Signaling

In many hematologic malignancies, canonical genomic alterations represent important diagnostic and prognostic markers. Yet in many cases, it is unclear what role these individual alterations play in driving and maintaining tumorigenesis. We aim to use CRISPR/Cas9 genome engineering to generate in vitro models of cancers from the “ground up” in normal B-lymphocytes. We will characterize global changes in protein abundance and signaling caused by these isolated genomic alterations using quantitative proteomics and phosphoproteomics. These studies will reveal the critical building blocks of tumorigenesis as well as demonstrate how isolated genome-level changes lead to functional changes at the level of the cancer proteome.