Utilizing Multi-omics to Facilitate Cancer Biology Research

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Project Summary As a member of the E. Alejandro Sweet-Cordero laboratory my efforts are directed at executing the computational aspects of the grants, manuscripts, and the general goals of the lab as well as mentoring other lab members. The goals of our projects are to study the mechanism of cancer progression and obtain clinically relevant insights for pediatric and adult solid tumors. The R50 NCI Research Specialist Award would provide me with the necessary funds to continue to further develop my computational tools and ongoing support for the following NCI-funded projects: (1) Development of Advanced Preclinical Models for Pediatric Solid Tumors (R01CA243555). There are three main goals to this project: a) verify that matched patient tissue and patient- derived xenografts (PDX) or PDX-derived cell lines are transcriptionally and molecularly similar; b) utilize high- throughput analyses to nominate drug targets for testing, and c) study drug resistance using single-cell RNAseq technologies. (2) Development of Novel Protein-based Therapeutics for Lung Cancer (R01CA225103). The main goals of this grant are to understand the biology of CLCF1-CNTFR as it relates to adult lung cancer and evaluate the synergistic outcomes of the engineered “decoy” CNTFR receptor (eCNTFR) with other compounds (e.g., eCNTFR+ PDL1 checkpoint inhibitor). (3) Investigate the Role of Long Non-coding RNAs (lncRNA) in Sarcoma Pathogenesis (R01CA211657). The goals of this grant are to elucidate the role of lncRNA EWSAT1/2 in chromatin remodeling at EWS-FLI repressed enhancer sites, utilizing ChIRP-Seq and ATACseq. Other lncRNAs revealed from a prior lncRNA CRISPR-mediated interference screen will also be investigated for their role in Ewing Sarcoma using both in vitro and in vivo models. My ongoing efforts to develop software and computational pipelines will not only go toward the goals of these NCI grants but also align with my long-term career goals and benefit the broader cancer research community.