Abstract IA11: Combinatorial screens in Drosophila cells

Our laboratory is combining a number of omics approaches (Mass Spec, RNAi, phosphoproteomics, and transcriptomics) to expand our understanding of the structure of signaling networks. Applying these approaches has allowed us to identify additional components of a number of signaling networks including the MAPK/ERK, AKT/PI3K, Hippo, Insulin and autophagy pathways (Friedman et al., 2011; Vinayagam et al., 2013; Neumüller et al., 2013; Kwon et al., 2013; Zirin et al., 2015; Vinayagam et al., 2016). An important finding from large-scale studies is that we could only functionally validate about half of the network components using single-gene loss of function studies, suggesting a high level of functional redundancy within network. For example, using Mass Spec we generated an Insulin pathway interactome of about 560 proteins and only 50% were found to affect pathway output as measured using phospho-specific antibodies (Vinayagam et al., 2016). To interrogate redundancy, we established a robust platform for performing combinatorial screens and used it to identify synthetic lethal (SL) interactions with a number of tumor suppressors such as TSC1 and TSC2 (Housden et al., 2015). Importantly, almost all the SL interactions we discovered in the fly screens turned out to be conserved in mammalian cells (collaboration with Alex Valvezan and Brendan Manning). These studies have led to identification of promising drug targets, and, as some of these are known targets of FDA approved ...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Model Organisms to Identify Synthetic Lethal Interactions: Oral Presentations - Invited Abstracts Source Type: research