Anthony M.C. Brown, Ph.D.

Research

Research in my laboratory centers on basic mechanisms of Wnt signaling, and understanding how altered Wnt signaling contributes to cancer. The role of stem-like cells in tumorigenesis is of particular interest and a long-term goal is to develop novel strategies for cancer prevention and treatment. Recently, we have focused on the determinants of Wnt signaling specificity (canonical versus non-canonical), the role of individual receptor components in signal transduction, and the role of Dishevelled (Dvl) proteins in Wnt signaling pathways. We have found that phosphorylation of Dvl is a manifestation of non-canonical signaling but is also induced by Wnts that activate the canonical pathway. This implies that many Wnts consistently activate both signaling mechanisms in the same cells. Dvl phosphorylation now provides a robust biochemical assay for further investigation of non-canonical Wnt signaling. Our in vivo studies focus on mouse models of breast cancer. We are manipulating specific aspects of Wnt signaling in the mammary gland to elucidate the functions of these pathways in normal development and cancer.