Unbiased Combinatorial Genomic Approaches to Identify Alternative Therapeutic Targets within the TSC Signaling Network
Abstract
The goal of this project was to identify robust synthetic lethal interactions between TSC and kinases and phosphatases by taking advantage of the evolutionary conservation of the pathway. We first identified such interactions in Drosophila cells and tested the candidates in TSC human patient cells. We identified three hits (mRNA-Cap, Pitslre and CycT) that scored as synthetic lethal with both TSC1 and TSC2 mutations in Drosophila and validated the mammalian orthologs of the three hits as having synthetic lethal relationships with TSC2 in both mouse and human cells, as their depletion selectively decreases the viability of TSC2 null cells. These candidates are now strong drug candidates for TSC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- ADA624180
Entities
People
- Brendan D Manning
- Norbert Perrimon
Organizations
- Harvard University