Dana M. Brantley-Sieders, PhD
1161 21st Avenue South, Medical Center North, Room / Suite T-3113, Nashville, TN 37232-2681
Assistant Professor of Medicine
Our research program focuses on molecular mechanisms that regulate breast tumor growth, tumor angiogenesis, and host-tumor interactions. Members of the Eph family of receptor tyrosine kinases regulate cell growth/survival, motility, and angiogenic remodeling during embryogenesis. More recently, several members of this family have been linked to tumor progression and neovascularization, including breast cancer.
Overexpression of one family member in particular, EphA2, correlates negatively with overall and recurrence-free survival in breast cancer patients. Our laboratory along with others has linked EphA2 signaling to Erk-dependent growth and Rac-dependent invasion in cell culture and animal models of breast cancer, as well as neovascularization and Herceptin-resistance. Moreover, EphA2 physically and functionally interacts with EGF receptor family members, including EGFR and HER2, in the context of breast cancer. More recently, we found EphA2 expression levels are highest within the Triple negative/basal-like subtype of breast cancer. Thus, EphA2 represents a new molecular target for cancer therapy, especially given its simultaneous influence on both tumor cells and the blood vessels within the surrounding microenvironment.
More recently, we have initiated an exciting collaboration with Biomedical Engineering to couple advanced nanocarrier siRNA delivery platforms to targeting conventionally undruggable molecular drivers of cancer in our clinically relevant models of breast cancer. Recent studies have validated one nanoparticle platform in targeting rictor/mTORC2 in breast cancer.
Ongoing studies in the laboratory focus on:
1. The role of EphA2 ligand-independent signaling in lipid metabolism in the context of breast cancer
2. The role of EphA2 signaling in Triple Negative/basal-like breast cancer growth and invasion
3. The role of EphA2 in angiocrine-mediated breast cancer growth and invasion
4. Targeting conventionally undruggable molecular drivers of cancer using advanced nanocarrier siRNA delivery systems