Applying Molecular and Functional Genomics to Identify Biomarkers for Diagnosing and Treating Cancer

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SUMMARY This application will support an exceptional Research Specialist who is essential to the scientific direction, operation, and enhancement of a productive research group. The Research Specialist and Unit Director have worked together since 2009, closely since 2017. The major goal of the Unit Director’s group is to develop inexpensive, non-invasive methods that can identify individuals who are at risk of non-small cell lung cancer and use the information obtained to improve therapy. As part of this effort, the Research Specialist is responsible for collecting and maintaining The Wistar Institute biorepository of 3,350 non-small cell lung cancer patient samples, including PBMC, PAXgene, and plasma. The Director’s group also manages Genomics and Bioinformatics Cores, which support ~15 NCI-funded research projects. Last, the Unit Director and Research Specialist collaborate with other Wistar investigators and industry to: identify a gene expression signature that can subclassify glioblastoma, characterize a potential new tumor antigen generated by the fusion of 2 LNC- RNAs, and understand the role of A-to-I RNA editing in metastasis. The Research Specialist has expertise in cell and molecular biology and extensive experience in multiple genomics and cell biology techniques. She also has a strong interest in translational research and has been able to apply the knowledge generated to design more effective therapies for lung cancer and glioblastoma. She is first author on 17 of the 26 papers she has published and on 9 of the 17 papers published during her 12-year tenure at Wistar. Many are in highly ranked journals including Nature Cell Biology, PNAS, EMBO, and Cell. She is listed on 5 U.S. patents. The Research Specialist’s expertise in a wide variety of molecular biology techniques is critical for the success of all main projects. It makes her ideally suited to conduct the studies on developing lung cancer genetic and biomarker signatures using genomic based assays; it also enables her to identify areas where improvements/changes are needed and independently develop protocols to improve the variety of assays employed. Since the Showe lab has been the primary developer of new genomics technologies for adoption by the Genomics Core, the Research Specialist’s background is essential for being able to develop these new platforms, including TCR-seq, the assessment of various platforms for single cell genomics, and the implementation of various NanoString technologies. For most work, the Research Specialist is the primary interface with Bioinformatics, ensuring that genomic data is correctly interpreted for analysis. The Research Specialist is essential not only for completing the proposed work of the next five years, but also for identifying new directions and new research and clinical collaborations. In summary, this award will allow the Research Specialist to continue making significant contributions to identifying circulating biomarkers for early cancer detection and to understanding the mechanisms of metastasis and oncogenesis. It will advance the identification of circulating biomarkers for lung cancer, support multiple NCI-funded groups via the Genomics Core, and enhance novel collaborations.