The Ellis laboratory is a dedicated translational oncology research program, rich with individual expertise and collaborative studies, which focuses on generating new and optimizing current treatment strategies for patients across the breast cancer spectrum. In order to develop precision diagnostics, the Ellis lab is interested in delineating mechanisms of resistance to standard-of-care therapeutics and metastasis for each breast tumor subtype. Ongoing studies are investigating the underlying mechanisms and therapeutic strategies to treat ESR1 (gene encoding estrogen receptor alpha) mutations and translocations, NF1 loss, DNA damage repair defects, and HER2 mutations. In addition to utilizing standard in vitro and in vivo xenograft animal models, research data is complemented through the use of cutting-edge patient-derived “Washington Human in Mouse” (WHIM) xenograft models (Li et al., Cell Rep., 2013). These WHIM models enables us to have experimental models at the bench that link clinical responses seen in patients, allow more accurate studies on breast cancer mechanisms, and identify new drug treatments.
The Ellis laboratory also engages in frontier-level approaches that integrate big data science (“omics”) to gain a better overall understanding of how genetic aberrations in breast cancer cells influence disease characteristics and therapeutic response. The journey from gene to gene expression to protein expression to protein activation is an extremely complex process under precise regulatory control. Our pioneering collaborative studies have revealed a more complete “picture” of how gene copy number aberrations affects protein activation through the use of combinatorial “omics” analyses (Mertins et al., Nature, 2016). Such proteogenomic (linking proteins and genes) analysis continues to be of intense interest. We are now extending this approach to our patient-derived xenograft models, thereby, supporting the development of tailored therapeutic approaches.