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General Research Interests
My research seeks to understand the basic principles of
how vertebrate
embryos develop. Understanding embryonic development is of fundamental
importance to general biological knowledge and to medicine. Many basic
principles of biochemistry and cellular biology have been revealed by
embryology, and very often these principles have proven relevant to
understanding the mechanisms of disease. The causes of a variety of birth
defects, which are obviously of embryonic origin, have been uncovered
through the study of “model” animals such as mice, flies,
worms and frogs. The molecular origins of diseases such as cancer, which
is characterized by uncontrolled growth and abnormal differentiation, are
also much better understood today through the efforts of molecular
embryology.
Research Projects
Amphibian Development
We study molecular mechanisms of animal development, with
primary emphasis on cell fate specification and pattern formation by
inductive (cell-to-cell) signaling. We use the frogs Xenopus laevis and Xenopus
tropicalis in our investigations, and our broad focus is on
regulation of early development by the two principal branches of TGFβ
signaling pathways: Vg1/nodal/activin and BMP. Present efforts seek to
identify and understand the biochemical and embryonic functions of
modulators of TGFβ signal transduction, such as Smad-interacting
factors and ubiquitin ligases. We also study the more general question of
how ubiquitin-mediated protein degradation regulates early development.
Our basic experimental approach is to study the effects of gain and loss
of function in embryos and cultured cells, on gene candidates selected
from our own protein-protein interaction (PPI) screens, as well as PPI and
differential expression information from systems biology studies. We also
select candidate genes based on potential functions revealed in other
animal systems.
Lab Members working on These Projects: Jerry, Yasuno, Bill, Lidia, Youngja, Mary, and Gina,
Anemone Development and Regeneration
While Xenopus has been the
traditional study organism in the lab, our scope is expanding to include
studies of the sea anemone Nematostella
vectensis. Sea anemones belong to the phylum Cnidaria, which also
includes corals, jellyfish and hydroids (e.g. Hydra). We are interested in
sea anemones because they are an ancient group among the metazoa and are
considered “basal” to nearly all other animals except sponges
and ctenophores. The last time cnidarians and vertebrates shared a common
ancestor was about 700 million years ago. Therefore, by comparing the
developmental programs of frog and sea anemone embryos we will gain new
insights into the evolution and deployment of genetic and biochemical
pathways that govern development. Furthermore, sea anemones and frogs
can regenerate missing parts, and sea anemones in particular are robust
regenerators. We have begun to study fundamental aspects of sea anemone
regeneration and will compare our findings with findings made with other
regenerating model systems, such as limbs, organs or specific cell types
(including stem cells). These comparisons will help reveal principals that
are common, as well as unique, to different regeneration situations.
- Transcriptome of regenerating N.
vectensis
- Contribution of signaling pathway members to N. vectensis regeneration
Lab Members working on This Project: Jerry, Bill, Lidia, Matt, and Gina,
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