Investigating the role of metabolism in metastasizing breast cancer cells

Preliminary data from the Fendt lab showed that pretreating mice with tumor-conditioned media (TCM) increased metastasis formation and aspartate levels in the pre-metastatic niche.  Thus, I hypothesize that inhibiting aspartate metabolism would target disseminated cancer cells in distant organs.  With this project I will deliver 1) the biochemical role of aspartate in supporting the disseminated cancer cells; 2) the mechanism by which secreted factors elevate aspartate levels in the lung pre-metastatic niche 3) how these mehanisms can be exploited as a therapateutic strategy against disseminated cancer cells.  Methodologically, I will use breast cancer cell lines, syngeneic, xenograft, and PDX mouse models, metabolomics, 13C trancer analysis, immunoblotting, IHC, single-cell RNA sequencing, genetic engineering, and pharmacologic interventions.  Ultimately, I will provide an understanding of metabolic dependencies of metastasis which can be translated into novel therapeutic concepts.