The Home Page of Angela Barth, Ph.D.

Postdoctoral fellow in the laboratory of Dr. W. James Nelson, Stanford University

Department of Molecular and Cellular Physiology

Beckman Center B109/ 300 Pasteur Drive

Stanford University School of Medicine

Stanford, CA 94305-5426

Tel: (650) 723 9788, Fax: (650) 498 5286



Summary of Research Interests

Current Research





Summary of Research Interests

I am interested in understanding how epithelial cells coordinate basic processes such as adhesion, migration, proliferation and differentiation in response to extracellular signals during organogenesis. The morphogenesis of organs, such as the mammary gland, the lung, the intestine and the kidney, requires the outgrowth of epithelial cells into highly structured and functionally specialized tissues. Kidney development is an excellent example for the complexity of epithelial morphogenesis. During kidney development, epithelial cells undergo tubulogenesis, a growth factor-regulated process of complex morphogenetic rearrangements, to form the tubular systems of the collecting duct and nephrons. In my postdoctoral work with Dr. James Nelson at the Stanford University School of Medicine, I have used hepatocyte growth factor (HGF)-induced tubulogenesis of Madin-Darby canine kidney (MDCK) cells as an in vitro system to study the molecular mechanisms of epithelial morphogenesis. My studies suggest that the adherens junction and signaling protein beta-catenin has key functions in epithelial morphogenesis.

The goal of my future research is to define the mechanism(s) by which beta-catenin regulates epithelial morphogenesis. beta-catenin has important structural as well as signaling functions. It is essential for the adhesion function of cadherins, a family of Ca2+-dependent homophilic cell-cell adhesion proteins, by linking them to alpha-catenin and the actin cytoskeleton. It is part of the Wnt signaling pathway which is important for pattern formation during embryonic development. beta-catenin modifies gene expression in response to the Wnt signal by interacting with transcription factors of the T cell factor/Lymphoid enhancer-binding factor family. Furthermore, beta-catenin binds to the adenomatous polyposis coli (APC) protein, the product of a tumor suppressor gene mutated in most colorectal adenomas. APC protein has been shown to downregulate the beta-catenin/transcription factor complex by stimulating beta-catenin degradation, and defects in this regulation have been associated with cancer formation. The results of my postdoctoral work suggest that the APC protein/beta-catenin complex has an additional function in regulating microtubule dynamics during the morphogenetic movements of epithelial cells. The association of beta-catenin with structural components involved in adhesion and in motility, and its role in regulating gene expression, suggest that it may be involved in coordinating these basic cellular processes in response to extracellular signals. My future research will combine methods of molecular biology and biochemistry with specialized cell biological and microscopical techniques, to characterize the functions of the E-cadherin/beta-catenin and APC protein/beta-catenin complexes, and to investigate the role of beta-catenin in regulating gene expression during epithelial morphogenesis.