Molecular Mechanisms of TGF-ß Signaling In Embryonic Development

 

A fundamental aspect of embryonic development is the ability of cells to communicate with one another and influence cell fate through the use of inter-cellular signaling. Such interactions are also crucial for regulated cell proliferation and differentiation in adult organisms. The Transforming Growth Factor-ß (TGF-ß) superfamily of secreted proteins represents an important class of signaling molecules that are involved in development and disease, in organisms ranging from hydra to humans. For example TGF-ß ligands such as Bone Morphogenetic Proteins (BMPs) and activins regulate cell proliferation (tumor suppression), bone differentiation, immune response, neuronal function, endocrine activity, and embryonic development.

 

My lab is interested in the molecular mechanisms by which cells perceive TGF-ß signals, integrate information from multiple pathways, and respond by regulating the transcription of appropriate target genes. Our aim is to understand how the activity of these ligands is regulated and transduced, particularly in the context of embryonic and nervous system development in Drosophila. Despite the evolutionary distance, fundamental aspects of the TGF-ß/BMP signaling pathway show remarkable conservation from flies to humans. We anticipate that our studies will lead not only to understanding embryonic development and growth, but also provide crucial insights into the basis of human diseases such as pancreatic and colon cancers, as well as fibrodysplasia ossificans progressiva, and hereditary hemorrhagic telangiectasia, that are caused by misregulation of TGF-ß signaling. We are taking a variety of approaches including classical and molecular genetics, biochemistry, tissue culture, imaging, and cross-species studies. Some of the questions we are currently focusing on are:

 

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