Stuart J. Newfeld, Ph.D.

Associate Professor
School of Life Sciences
Arizona State University

Tempe, AZ 85287-4501
Phone: (480)965-6042 / 965-0382
Email: newfeld [at] asu.edu

Newfeld Smad Family cover
Cover Illustration for the first book on the Smad Family. Click on image for PDF view.

Newfeld Genetics cover
November 2006 cover of Genetics. Click on image for PDF view.

Research Summary: Growth Factor Signaling in Development and Cancer

In multicellular organisms, communication between cells is required for embryonic development and to prevent tumors in adults. Signaling molecules of the Transforming Growth Factor-β (TGF-β) and Wingless/int-1 (Wnt) families regulate developmental events in many species. Some events require combinatorial input from both pathways but how TGF-β and Wnt signals are integrated is not well known. Two important signaling proteins in Drosophila are Decapentaplegic (Dpp, TGF-β family) and Wingless (Wg, Wnt family). We have shown that combinatorial signaling by these two pathways regulates embryonic cardio-pulmonary development. Dpp expression in a medial region of the dorsal ectoderm is required for Heart development and expression in the posterior dorsal ectoderm is required for Posterior Spiracle development (these will become larval airways). Interestingly, each site of Dpp expression is regulated by a distinct mechanism of combinatorial signaling involving the Wg and Dpp pathways. Alternatively, many components of the TGF-β and Wnt pathways are tumor suppressors in adults. For example, mutations in TGF-β signal transducers (Smad genes) are involved in 140,000 new cancer cases in the US each year. Using a transgenic assay system we discovered that a subset of Smad tumor mutations generate ectopic activation of the Wg pathway. Our strategy of conducting complementary studies of normal embryonic and aberrant tumorigenic interactions between the TGF-β and Wnt pathways has provided considerable new information on molecular mechanisms involved in development and cancer.