Research Interests:

My laboratory studies mechanisms underlying cell survival and migration during embryogenesis and disease. We are particularly interested in embryonic signaling pathways that are re-activated in tumors to promote cancer metastasis. An excellent model of cell migration during development is the neural crest, a multipotent cell population that migrates extensively in the vertebrate embryo to generate a variety of cell types, including pigment cells, neurons, glia and elements of the craniofacial skeleton. Neural crest progenitors are initially generated in the neuroepithelium of the neural tube, so they must first undergo an epithelial-mesenchymal transition (EMT) to form premigratory neural crest cells. These cells then divide and navigate through a number of embryonic tissues that secrete potential pro-apoptotic signals, before arriving at their final destination to differentiate. Thus, neural crest cells have evolved mechanisms to coordinate a number of cellular processes that involve regulation of cell survival, proliferation and migration, as well as modifications of cell-cell adhesion that involve dynamic interactions with the extracellular matrix. Disrupting these processes during human development causes a number of congenital diseases (neurocristopathies), and cancers, such as melanoma and neuroblastoma. Importantly, recent studies have shown that ‘re-activation’ of neural crest transcription factors in primary tumors promotes tumor invasiveness and metastasis.
To study neural crest migration and metastasis, we use the zebrafish model because the optically clear embryos and adult pigment mutants allow fluorescently labeled cells and tumors to be monitored using real-time imaging techniques. In addition, the molecular pathways underlying mammalian embryonic development are highly conserved in zebrafish, and a number of zebrafish models of human diseases are now established, including neural crest-derived cancers. Also, cell transplantation experiments can be performed in embryos and adult fish, allowing cell autonomous and non-autonomous mechanisms of cell migration and metastasis to be investigated. Thus, the attributes of the zebrafish system provide a unique opportunity to determine how developmental mechanisms that control cell migration during development are subverted in pediatric diseases and cancer metastasis.