(6da) Engineering Approaches to Elucidate Mechanisms of Physiologically Relevant Cellular Behaviors in Cancer

Approximately 90% of cancer related deaths worldwide occur because of metastasis of the primary tumor to other organs. The tumor microenvironment plays a key role in metastatic disease progression; however the associated mechanisms are far from being unraveled. The goal of my research program is develop tools to systematically study these processes and dissect relevant mechanisms in vitro and in vivo. During my doctoral research at the Ohio State University, I developed brain mimetic biomaterial systems (e.g., hydrogels, electrospun nanofibers) that mimic several features of the in vivo tumor microenvironment for investigating migration of patient derived human glioblastoma multiforme (GBM) tumor cells. These three dimensional (3D) cell culture systems recapitulate in vivo like morphology, migration, and molecular signatures of GBMs as opposed to traditionally studied 2D cell culture systems. Such biomimetic cell culture models will allow for patient tailored bioassays where patient tumor biopsies can be examined and several drug combinations can tested for personalized medicine, thereby guiding patient care and treatment decisions with the potential to transform current cancer treatment. During my postdoctoral research at Northwestern University, I developed microporous poly(ε-caprolactone) (PCL) biomaterial scaffolds for early detection and treatment of breast cancer metastasis. I also discovered and demonstrated the efficacy a novel therapeutic combination of cyclin dependent kinase-2 (CDK2) inhibitors and Eribulin for the treatment of triple negative breast cancer. To investigate the mechanism of drug action, I utilized a live cellular array that provides high-throughput analysis of dynamic transcription factor activities. This poster will highlight the application of these tools in vitro and in vivo, which will provide a foundation to elucidate mechanisms of tumor progression and subsequently develop early detection and therapeutic strategies.