Our lab is interested in the ways in which cells break symmetry, and initiate and maintain spatial asymmetries. Asymmetries can form as cells polarize, or can occur within cells, for instance during mitosis. Gradients of proteins or other molecules can create asymmetries that the cell uses to specify orientations and subcellular locations. Carcinomas arise from epithelial cells, and tumor progression involves a loss of polarity, so an understanding of cell polarity is important in the identification of novel therapeutic approaches to cancer. Cell polarity is usually lost early during tumor progression, and several polarity proteins have been identified as tumor suppressors.
We have four major programs ongoing a?? on the mechanisms that determine the polarization of mammalian epithelial cells; on the control of mammary gland morphogenesis and breast cancer initiation and metastasis; on the role of septins in cell polarity and in DNA repair; and on RNA localization.
We use a range of approaches to study these cell processes, including a new mammary gland regeneration model in which mammary stem cells are transduced with lentivirus then transplanted into the cleared fat pads of recipient mice, where the cells regenerate an entire new mammary ductal tree. We have also developed new methods to purify RNA binding proteins, and to study miRNA function in mammary gland morphogenesis. In vitro studies include 3D culture of mammary gland organoids, human breast tissue organotypic cultures, and renal epithelial cysts. We are using these systems to explore the mechanisms that control spindle orientation during mitosis; the roles of small GTPases in cell polarization; and the mechanisms underlying asymmetric cell divisions of mammary stem cells.