Digestive diseases affect millions of Americans each year, and a significant number will die
from them. The main culprits of these diseases are disrupted cellular mechanisms for
homeostatic control and deficient repair mechanisms. Repair mechanisms play an important
role in healing after natural events that damage the digestive tract and also after gastrointestinal
surgery. Accordingly, the ability to regenerate intestinal tissue could be an important therapeutic
tool. Although advances have been made on the regeneration of the luminal layer of the
vertebrate digestive tract, little is known about the regeneration of other cells and tissue layers
or of the organ as a whole. Part of the problem is that in vertebrates, these cells or tissue layers
have limited regenerative capacity.
This proposal uses a novel model system, an echinoderm, to study intestinal regeneration.
Among deuterostomes, echinoderms comprise some of the closest relative to vertebrates that
have amazing regenerative capacities. One of these organisms, the sea cucumber Holothuria
glaberrima, possesses the innate ability to regenerate their entire digestive tract after it is self-
The present proposal searches to establish the role of cellular mechanisms and their
underlying molecular bases on the regeneration of H. glaberrima intestine. Cellular proliferation,
cell death and injury activation of oxidative stress and inflammation will be probed
pharmacologically to determine whether they in fact are involved in intestinal regeneration and
whether they act in the triggering of the regeneration response as inducers of other events or as
downstream effectors. Additional experiments will compare the gene expression profile of
normal, non-regenerating and regenerating mesenteries. These experiments will serve to further
identify the genes associated with the early regenerative events in intestinal regeneration.
Our results, could serve as the basis for the development of new therapeutics/drugs that
modulate regenerative processes. They will also provide important information to other fields of
research, including wound healing, immunology, cell biology, genomics and phylogenetics.
Finally, the outcome of these experiments will bring us closer to a better understanding of
regenerative processes in general.