Genome-Wide RNA Interference Screens to Identify Factors Involved in Cancer Initiation and Progression
Our lab has a broad interest in understanding the mechanisms that regulate gene expression in eukaryotes and the role of gene expression in various human disease states. We are particularly interested in how transcriptional regulation plays a role in cancer initiation and progression. For example, some oncogenes and tumor-suppressor genes are themselves transcription factors; inactivation of genes critical for cancer development often occurs by epigenetic silencing; some genes involved in cellular growth control and apoptosis (programmed cell death) are selectively transcribed in cancer or normal cells; and some apoptotic pathways are transcriptionally regulated.
We are using a variety of molecular biological, genetic, and biochemical approaches to (1) study these transcription-based processes, (2) delineate the relevant regulatory pathways, and (3) identify the components in these pathways. Currently, we are performing a series of genome-wide RNA interference (RNAi) screens to identify factors involved in oncogene-induced epigenetic silencing, oncogene-induced senescence, transcriptional regulation of tumor-suppressor genes, and the induction of apoptosis by chemotherapeutic agents. We are also using genome-wide RNAi screens to identify new tumor-suppressor genes and genes that regulate metastasis. The EXROP student will learn the principles of designing an effective RNAi-screening procedure and gain experience in a variety of biochemical and molecular biology techniques (e.g., recombinant DNA cloning, DNA sequencing, qualitative and quantitative PCR and RT-PCR, RNAi, immunoblotting, and chromatin immunoprecipitation) and/or cell biology protocols (e.g., mammalian tissue culture, apoptosis assays, cell proliferation assays, in vitro metastasis assays).