TI-3D Research Highlights : Edward Marcotte : Neural Tube Defects
Directed identification of ciliogenic genes impacting neural tube defects
In collaboration with John Wallingford
Neural tube defects, including spina bifida, are among the most common and debilitating human birth defects, affecting ~1 in 1000 pregnancies. This project’s goal was to apply new computational methods for discovering candidate genes involved in neural tube birth defects, then to test those genes in a vertebrate model of neural tube closure (the frog Xenopus laevis). At the end of our year of TI-3D funding, we have already successfully found 2 new genes whose inactivation can induce neural tube birth defects in a vertebrate, as shown by us for the first time. With these data, we successfully applied for a federal grant from the National Institutes of Health, leveraging our TI-3D grant moneys by >14-fold. We have filed a patent on the new computational methods for identifying candidate disease genes and are moving towards licensing the technology. Our computational methods also revealed candidate genes in diverse other diseases and disease-relevant processes, including Waardenburg syndrome (characterized by craniofacial, hearing, and pigmentation abnormalities), breast cancer, and angiogenesis. We confirmed one gene as a new regulator of angiogenesis in animals and human in vitro cell-based angiogenesis assays, serving as a possible target for angiogenesis inhibitors suitable for anti-tumor chemotherapy.
Ryan S. Gray, Phil B. Abitua, Bogdan J. Wlodarczyk, Otis Blanchard, Insuk Lee, Greg Weiss, Edward M. Marcotte, John B. Wallingford and Richard H. Finnell. The planar cell polarity effector protein Fuzzy is essential for targeted membrane trafficking, ciliogenesis, and mouse embryonic development. Nature Cell Biology 11, 1225 – 1232 (2009).