Genetic screen using RNAi and CRISPR/Cas9 libraries is a powerful approach to interrogate the cancer genome for functional vulnerabilities. We have developed technologies to conduct rapid and cost-effective shRNA and sgRNA library screens. PURPOSE. In this project we aim to carry out loss-of-function and gain-of-function genetic screens using RNAi and CRISPR/Cas9 libraries to study genetic vulnerabilities in cancer cells and identify mechanisms of drug resistance. We will also collaborate with other investigators (primarily investigators in the NIH Intramural Program) to enable them to conduct screens in cancer cell lines. SIGNIFICANT MATERIALS AND METHODS. Pooled shRNA and CRISP/Cas9 library targeting most annotated human genes. ACCOMPLISHMENT. We have completed several screens in a number of different cancer disease areas. We are studying candidate genes from these screens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011438-06
Application #
9556575
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Jossé, Rozenn; Zhang, Yong-Wei; Giroux, Valentin et al. (2015) Activation of RAF1 (c-RAF) by the Marine Alkaloid Lasonolide A Induces Rapid Premature Chromosome Condensation. Mar Drugs 13:3625-39
Kessler, Jessica D; Kahle, Kristopher T; Sun, Tingting et al. (2012) A SUMOylation-dependent transcriptional subprogram is required for Myc-driven tumorigenesis. Science 335:348-53
Zhao, Jie; Jitkaew, Siriporn; Cai, Zhenyu et al. (2012) Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci U S A 109:5322-7
Weng, Meng-Tzu; Lee, Jih-Hsiang; Wei, Shu-Chen et al. (2012) Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells. Proc Natl Acad Sci U S A 109:E3659-67