Technological advances have revolutionized the genome-scale profiling of DNA copy number and sequence, DNA and chromatin modification, and gene expression and have substantially enhanced our understanding of the molecular changes that underlie many cancers. However, functionalizing these findings in a systematic manner remains a challenge. To address this challenge I, and others, developed experimental strategies for the discovery and elucidation of gene function by exploiting the RNA interference (RNAi) gene silencing mechanism to generate loss-of-function (LOF) phenotypes. My research interests build on my experience in the nucleic acid delivery/gene therapy research field, my work on the RNAi mechanism (including studies establishing the existence of RNAi in mammalian cells), and my independent and collaborative endeavors developing RNAi based analysis and screening approaches for the study of gene function.

My laboratory uses functional genetic approaches induced by RNAi and other DNA or RNA-based technologies to interrogate specific aspects of the genetic, transcriptional, and cell-signaling alterations observed in cancer cells. Current research is focused on the development of new treatment strategies for cancers driven by fusion oncoproteins. Fusion or chimeric oncoproteins represent a unique vulnerability as they are only expressed within tumor cells. However, little is known about how tumor cells co-opt cellular processes to express, from rearranged DNA, an in-frame fusion transcript encoding a chimeric functional protein and so we are using functional genetic approaches to identify genes required for the expression or activity of fusion oncoproteins. This work will further our understanding of how the expression of this important class of cancer oncogenes is regulated and how they may be optimally targeted.