Viral-based insertional mutagenesis as a tool to discover chemotherapy-resistance genes

Description of projects available to graduate students:
Background: Chemotherapeutic agents such as DNA alkylating agents and PARP inhibitors are used alone and in combination in cancer therapy yet in many cases, resistance limits efficacy. Selective, personalized therapy would provide an opportunity to utilize chemotherapeutic agents strategically. However, not all genes involved in resistance to these agents are currently known.

Project Description: This project will use a lentiviral-based selection tool to identify genes that provide resistance to chemotherapies such as the alkylating agent temozolomide and inhibitors of the DNA repair protein PARP1. Transduced cells are selected and genes that confer resistance will be identified by deep sequencing and validated using select shRNA and cellular response analyses.

Techniques graduate student will learn:
Human cell culture, lentiviral transduction, gene identification by deep sequencing and cell sensitivity assays.