Ian G. Macara, PhD
Small GTPases in nuclear transport and cell polarity
The Macara laboratory is interested in the mechanisms by which mammalian cells polarize, and how this polarization is lost during cancer progression. Carcinomas arise from epithelial cells, which during metastasis invade the basement membrane, migrate into blood vessels and extravasate to distant sites in the body. Invasion and migration require detachment of cells from the epithelial sheet, and loss of the normal apical/basal polarity. This process is called the epithelial-mesenchymal transition (EMT). The group identified a conserved polarity protein complex (the Par-6/Par-3/aPKC/Cdc42 complex) that is required for normal epithelial cell polarization. Recently, it discovered an unexpected link between this complex and the Rac GTPase, which is a key regulator of cell migration. The lab is also investigating a polarity protein called Scribble, which is a tumor suppressor in flies and which is targeted for destruction by the E6 protein of oncogenic human papillomavirus. Other polarity proteins under investigation include the septins, which have been implicated in leukemias. This work makes extensive use of the Advanced Microscopy Facility, for live-cell imaging, and the Biomolecular Research Facility, for molecular and proteomics analysis.
In collaboration with Dr. Deborah Lannigan, studies are underway to develop a lentivirus shRNA system to determine the role for polarity proteins in mammary gland development and breast cancer. This new technology will provide a powerful, cost-effective approach to testing gene function in a biologically and clinically relevant setting. The lab has also collaborated extensively with Dr. Todd Stukenberg, in studies on asymmetric cell division and cell polarity.