Projects

Expanded Clinical Application of RNA Sequencing

Approximately 95% of clinical molecular oncology tests assess DNA, with only 5% being RNA based. However, RNA-based testing has the potential to both complement and dramatically expand upon DNA-based testing. RNA testing has a higher yield in identification of clinically relevant gene fusions, and it allows examination of splice alterations, gene expression changes, and gene expression profiling signatures. Similar to the shift toward broader DNA-based molecular oncology assays, we expect that over time, we will see a shift from RNA-based assays focusing on a single gene or indication to more comprehensive transcriptome sequencing. Our group, in collaboration with many others at UNC, is drawing upon the extensive institutional experience with RNA sequencing and analysis, from projects such as The Cancer Genome Atlas, to the long-term goal of applying comprehensive transcriptome sequencing in the clinical setting.

Gene Expression Features and Signatures Predicting Tumor Behavior and Response to Therapies 

One of our initial projects related to the expanded clinical application of RNA sequencing involves development and application of gene expression features and signatures that predict tumor biology and response to therapies, initially immunotherapies. While immunotherapy regimens generally have a favorable side-effect profiles, they can result in significant treatment-related adverse events, more commonly when given in combinations. Current biomarkers used to guide selection of immunotherapy in clinical practice have limitations, and recently developed RNA sequencing-based gene signatures are promising biomarkers to guide use of immunotherapy in patients with advanced cancer. In collaboration with Drs. Kim, Perou, and Vincent, we are applying existing and novel immune signatures that have been modeled for clinical FFPE tissues. Development efforts are focused broadly on solid tumors with an emphasis on breast and endometrial cancers. Predictive signatures will be evaluated in a retrospective and then prospective clinical trial setting to evaluate clinical validity and utility.