Drosophila Development and Homeostasis Laboratory
We are using the fruit fly, Drosophila melanogaster, as a model of organ remodeling during development, homeostasis and disease. Fruit flies have an extensive tubular network called trachea that functions as both their lungs and their blood vessels, and transports gases and oxygen throughout their bodies via terminal tracheal cells. Similar to human lungs and blood vessels, the Drosophila tracheal system arises from epithelial progenitors that proliferate, differentiate, migrate and ramify to generate a complex network of interconnected tubes. Furthermore, the tracheal system undergoes remodeling in response to developmental and environmental signals, such as secreted growth factors and tissue hypoxia that activate conserved cellular programs. If these remodeling programs fail or become hyperactive, disease occurs and viability is compromised, similar to humans.
Our laboratory uses genetic, molecular and biochemical methods, as well as state-of-the art microscopy to study the Drosophila trachea aiming to identify novel genes and signalling pathways that control development and remodelling of mammalian lungs and blood vessels. We have established a model of developmental tracheal remodeling with similarities to lung development, as well as, a model of disease-induced tracheal remodeling with similarities to cancer angiogenesis. Using microarray profiling we identified the conserved Notch and Wingless/Wnt signaling pathways as key regulators of developmental remodeling through their action on the conserved transcription factor Cut. In addition, we characterized the tracheal system of the adult Drosophila intestine and found extensive tracheal remodeling in response to bacterial infection, inflammation and cancer. This "neotracheogenesis" process is driven by the conserved Hif1a/FGF/FGFR pathway and shares striking similarities with cancer-induced neoangiogenesis.
Our current efforts in the lab aim to:
1. Identify novel regulators of proliferation, differentiation and migration of tracheal progenitors during developmental remodeling.
2. Identify novel regulators of hypoxia-induced tracheal terminal cell remodelling
3. Identify regulators of intestinal neotracheogenesis during inflammation and cancer.
4. Assess the effect of tumor genetics in tracheal remodeling and cancer progression.