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The mechanisms that establish pattern and polarity in development have been the focus of our research for many years. In Drosophila, the axes of the egg and embryo are laid down during oogenesis. We have found that signaling between oocyte and follicle cells plays an important role in this process, and restricted EGF receptor activation is crucial in establishing both the AP and the DV axis of the egg. The EGF receptor pathway plays a determining role in several human diseases, notably, activating mutations in the receptor, or its downstream effectors, can lead to various forms of cancer. We have also found that the interaction of the EGFr pathway with the Notch pathway can lead to specific cell differentiation outcomes, where loss of either function results in complex phenotypes.
More recently, in collaboration with the laboratories of Stas Shvartsman and Rebecca Burdine at Princeton University, we have begun to model so called Rasopathy mutations that cause a specific syndrome in humans, by creating the identical mutations in Drosophila. Rasopathy is caused by germline mutations in Ras pathway components and is associated with a set of human developmental abnormalities, including cardiac defects and neurocognitive delays. We used quantitative assays to measure the signaling changes caused by specific mutations in MEK, a core component of the Ras pathway, which have been found in human patients. This study has given important insights into the effects of such mutations, and can be used to inform future drug treatments.
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