Unbiased Combinatorial Genomic Approaches to Identify Alternative Therapeutic Targets within the TSC Signaling Network

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2014
Accession Number
ADA610958

Entities

People

  • Brendan D Manning
  • Norbert Perrimon

Organizations

  • Harvard College

Tags

DTIC Thesaurus Topics

  • Cell Line
  • Cell Physiological Processes
  • Cell Size
  • Cells
  • Computer Programming
  • Culture Media
  • Culture Techniques
  • Cultured Cells
  • Diptera
  • Drosophila
  • Engineering
  • Genetic Engineering
  • Genetics
  • High Resolution
  • Protein-Protein Interactions
  • Statistical Analysis
  • Stem Cells

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology