Suzanne D. Conzen, MD
Defining anti-apoptotic signaling pathways in epithelial malignancies is essential for developing rational approaches to cancer therapy. The Conzen lab has identified an important role for activation of the glucocorticoid receptor (GR) in anti-apoptotic signaling of normal and malignant breast epithelial cells. The lab's overall goal is to define the specific molecular pathways initiated following GR activation in breast and other epithelial cancer cells in order to better understand anti-apoptotic signaling in a broader context, with the long term objective of targeting these novel pathways for tumor therapy. To this end, Dr. Conzen has analyzed serial gene expression profiles following GR activation as well as used traditional molecular biology and animal models to identify the molecular determinants of GR-initiated mammary epithelial cell survival. These approaches have demonstrated direct cross-talk between GR activation and the PI3-K and MAPK pathways via glucocorticoid-mediated transcriptional regulation of kinases and phosphatases. Using global gene expression data, the laboratory has developed software based on Dynamic Bayesian Network analysis to identify regulatory relationships between genes whose expression patterns change over time following GR activation. These predicted "gene-gene" relationships are investigated as components of downstream GR-mediated signaling pathways and are undergoing validation in more traditional in vitro and in vivo models of breast cancer; validated molecular determinants of cell survival signaling are also being investigated as markers of chemotherapy resistance in samples from patients enrolled on clinical trials.