My lab works on the Wnt/beta-catenin signaling pathway, which is conserved in all metazoans, where it plays many important roles during development, adult tissue homeostasis and regeneration. In addition, misregulation of the pathway is linked to several human pathologies, most notably cancer. Wnt signaling promotes the nuclear accumulation of beta-catenin, which binds to transcription factors of the TCF family to regulate Wnt target gene expression. All TCFs bind to DNA through a High Mobility Group (HMG) domain. Drosophila and C. elegans each contain a single TCF gene, and we have found that in addition to the HMG domain, they possess a second DNA binding domain called the C-clamp. We favor a model where the fly and worm TCFs recognize DNA through a combination of HMG and C-clamp binding to their respective DNA sites. Vertebrates contain four TCF genes encoding numerous isoforms, but most of these TCF isoforms do not contain a C-clamp. We are exploring the mechanism by which these TCFs locate their target genes in Xenopus embryos and human cell culture. A major goal of our research is to identify new Wnt targets in a variety of biological contexts. Dr. Cadigan received his Ph.D. degree from Dartmouth University in 1989 and has been a postdoctoral fellow at the University of Basel, Switzerland and Stanford University.
Field(s) of Study
- Signal Transduction and Transcriptional Regulation in Drosophila, C. elegans, Xenopus and human cells