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
email: angelab@leland.stanford.edu
Summary of Research Interests
Current Research
Movies
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.