Unbiased Combinatorial Genomic Approaches to Identify Alternative Therapeutic Targets within the TSC Signaling Network
Annual rept. 1 Jun 2013-31 May 2014
HARVARD COLL CAMBRIDGE MA PRESIDENT AND FELLOWS
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The long-term goal of this project is geared toward further defining the regulatory mechanisms impinging on the TSC-Rheb circuit and revealing therapeutic strategies to target this signaling network in genetic tumor syndromes and cancer. Specifically, we aim to establish a robust synthetic lethal screening method applied to the study of the TSC network, validate synthetic lethal pairs in an in vivo intestinal stem cell system, and determine whether synthetic lethal combinations found in Drosophila are relevant to mammalian networks. In the second year of funding we have made significant progress and generated the required mutant cell lines and performed a combinatorial screen that has led to some exciting leads that we are in the process of being validated in mammalian cells.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research