Interdisciplinary Initiatives Program Round 9 - 2018

Aaron Newman, Biomedical Data Science
Michael Clarke, Medicine (Oncology)

Just as normal cell types and tissues are ultimately derived from stem cells, increasing evidence suggests that human tumors may also arise from cancer stem cells, which have been implicated in tumor initiation, metastasis, and resistance to therapy. Despite their fundamental importance, our understanding of these "tumor initiating cells" (TICs) remains incomplete. For example, while previous studies have defined genetic markers that enrich for TICs, many markers are nevertheless non-specific, hindering the development of TIC-directed therapies. We hypothesize that an unbiased genomics approach for studying tumor cellular heterogeneity can improve the identification and characterization of clinically relevant tumor cell subsets, including TICs. To address this hypothesis, we are proposing a novel interdisciplinary framework for high-throughput cellular analysis. Our approach will allow us to interrogate tumor cellular heterogeneity in an unbiased and data-driven manner to identify and prioritize the most promising TIC candidates for functional validation. Although we will initially focus on breast cancer, which is the leading cause of new cancer cases and second most common cause of cancer-related deaths in females in the United States, the proposed approach will be generalizable to any malignancy, and in future work, we anticipate interrogating additional solid tumor types. The proposed interdisciplinary project, if successful, will accelerate the systematic identification and characterization of TICs, opening up new avenues of research for this critical, yet poorly understood component of tumor cellular ecosystems.