Research Summary: Growth Factor Signaling in Development and Cancer

Secreted signaling proteins in the Transforming Growth Factor-beta (TGF-beta) family perform a myriad of tasks during development and adult homeostasis while mutations that disrupt TGF-beta pathways can lead to disease. We have shown that the human genome encodes 33 TGF-beta family members, the fly 7 and the nematode 5. Transgenic studies, including in our lab, have shown that TGF-beta family members and other signaling pathway components can function across species, supporting the use of model organisms to understand human biology.

Employing the fruitfly Drosophila melanogaster we have identified numerous new roles for TGF-beta proteins, characterized how TGF-beta signal transduction works in responsive cells, and discovered numerous regulators of TGF-beta signal transduction. The central thread in our studies is Smad signal tranducers that I discovered years ago as a postdoc with colleagues at Harvard.  Studies showing that mutations in human Smad genes are associated with roughly 140,000 new cancer cases in the US each year kept our attention on the role of Smads as tumor suppressors. The adjacent journal covers are associated with papers from those investigations.

In 2012 we discovered a novel Smad regulatory protein called dCORL that is only expressed in neurons. It appears to interact with Smads in at least two different neurons and at different developmental stages. Given the fact that neurons do not divide, the specific role of dCORL and Smads in neurons remains elusive but we have recently connected these proteins to insulin signaling. The Science Talk below describes our studies of dCORL function in insulin producing neurons of the adult brain. The TPA Talk below describes my strategy for revising the science curriculum during my community service on the Board of Directors at a classical liberal arts high school.

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