The project supported by the Outstanding Investigator Award to the Unit Director, Dr. Peter K. Vogt, focuses on the transcriptional aspects of oncogenesis mediated by PI 3-kinase and by MYC. The starting points for this research are two discoveries made by the applicant: (1) MYC controls the majority of the long non-coding RNAs and (2) knock-in of the oncogenic PI 3-kinase mutation, H1047R, induces vast changes in the transcriptome that cannot be linked to PI 3-kinase activity. In pursuing this research, extensive use of NGS (next generation sequencing), RNAseq, design of CRISPR libraries to be used for gene activation and gene repression and analysis of complex proteomic data sets are required. The applicant is an expert in bioinformatics and computational biology and therefore is deeply involved in the analysis of the massive data sets generated by these approaches. He creates tools for the automated design of CRISPR-dCas9 guide RNAs, examines CCLE (Cancer Cell Line Encyclopedia) and TCGA (The Cancer Genome Atlas) data for long non-coding RNA expression and establishes new gene signatures associated with disease-relevant long non-coding RNA expression. The role of the applicant in the research of the unit director is critical and indispensable. The ultimate goal of this work is to contribute to an understanding of the unexplored and unexpected transcriptional activities of oncogenic MYC and oncogenic PI 3-kinase.
Long non-coding RNAs experience larger shifts in expression than coding genes. These shifts can result in changes to the expression of other cancer-specific genes. This work focuses on understanding the regulation of non-coding RNAs, their effects on cancer cells and their use as potential biomarkers.