High-throughput screening for pollutants that lead to mis-regulation of Hh signaling and cancer Research tool for studying how mis-regulation of H signaling pathway leads to cancer


Technology Mis-regulation of Hedgehog (Hh) signaling is implicated in a large number of human diseases such as skin cancer and brain cancer, as well as in a number of relatively common birth defects. In addition, Hh signaling plays a major role in regulating stem cell proliferation and growth in adults. The current invention provides new genetic tools for understanding Hh signaling in living vertebrate embryos and adults. These tools include proprietary hedgehog-pathway transgenic zebrafish lines that allow inducible activation, inactivation, and monitoring of Hh signaling within responding cells at any time in the life cycle of this vertebrate species. In addition to the temporal manipulation of Hh signaling, regulation of Hh signaling can also be controlled spatially within the whole organism through the use of a local heatshock device. Advantages Model Organism of Choice: The zebrafish is a model organism of choice for studying human development and diseases as well as for drug screening. It is a small vertebrate animal whose development is very similar to that of higher vertebrates including humans; it has a short generation time (~3 months), a transparent embryo that develops externally, and a large number of offspring. Cell-Autonomous Hh Manipulation: Hh signaling can be turned on or off within responding cells of the intact organism. Temporal and Spatial Hh Manipulation: Hh signaling can be activated or inactivated at any stage and place in the life history of the intact organism. Real-Time Monitoring by Fluorescence: The transgenic zebrafish Hh reporter lines allow real-time, fluorescence-mediated monitoring of Hh signaling in living embryos and adults under normal and various manipulated conditions.  

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