Wnt signaling in development, stem cells, and cancer
F.M.Kirby Neurobiology Center
Children's Hospital Boston
3 Blackfan Circle
We are interested in the signaling mechanisms by the Wnt family of secreted molecules. It has become clear that Wnt proteins are one of about half a dozen major families of conserved signaling proteins that guide embryonic development and adult homeostasis. We primarily focus on Wnt signaling in early vertebrate embryonic patterning, in cell polarity regulation (planar cell polarity and neuronal polarity), and in stem cell and cancer biology. We employ molecular, biochemical, embryological and genetic approaches in several experimental systems, including Xenopus embryos, mammalian and Drosophila cell cultures, and knockout mice.
Wnt/beta-catenin signaling: The canonical Wnt/beta-catenin signaling regulates beta-catenin phosphorylation/degradation and thus beta-catenin-dependent gene expression program. We are interested in understanding the molecular logic of this key developmental signaling pathway, including its dual-receptor system (the Frizzled family and LDL receptor-related proteins, LRP5 and LRP6), the dual-kinase system (CKI and GSK3) for both beta-catenin and the LRP5/6 coreceptors, and the connection from the receptors to beta-catenin regulation. Wnt signaling in cell polarity: Wnt signaling controls cell polarity, movements and tissue separation during vertebrate gastrulation via distinct signaling pathways, including Rho and Rac GTPases. These pathways are sometimes referred to as planar cell polarity signaling. Wnt/Frizzled signaling also regulates neuronal axon growth/polarity in mice. We are interested in understanding the molecular basis for these perhaps related phenomena. Wnt signaling in stem cell biology, cancer and diseases: The canonical Wnt/beta-catenin signaling is involved in stem cell regulation, cancer and other diseases such as osteoporosis, as hyperactive beta-catenin signaling leads to tumorigenesis and loss of function of LRP5 results in familial osteoporosis. We are interested in how Wnt signaling interfaces with the self-renewal property of stem cells, and the molecular links between Wnt signaling and human diseases.