The exocrine portion of the pancreas accounts for more than 90% of this organ's mass and its functions derive from acinar cells, which are highly specialized factories dedicated to synthesizing, storing, and secreting abundant amounts of digestive enzymes. The exocrine pancreas is highly relevant from a human health perspective, because it can be afflicted with debilitating and often fatal diseases, such as pancreatitis and pancreatic cancer. This application is built upon novel exciting information from our past studies on the role of the homeobox gene Prox1 in pancreas development, and more recent discoveries from my laboratory supporting that Prox1 is a novel regulator of acinar plasticity, oncogenic transformation, and inflammatory responses in the postnatal pancreas. Upon addressing various outstanding questions indicated in this proposal, the role of Prox1 in the gene regulatory network that establishes the identity of acinar cells will be determined, novel key players required for exocrine development and homeostasis will be identified, and new information on processes that regulate inflammatory responses in the pancreas will be disclosed. My ultimate goal is that through these investigations we generate knowledge that helps to improve the diagnosis, prevention, and cure of pancreatic diseases, and assists the production of human exocrine cells to be used in the clinic.
The exocrine pancreas produces and transports secretions that digest the food into components to be easily handled and absorbed by the intestine. Defects in exocrine pancreas development or function can lead to malabsorption and malnutrition. However, in more severe cases these defects can cause very debilitating and sometimes fatal diseases, for example pancreatitis and pancreatic cancer. Understanding the molecular and cellular bases of exocrine pancreas development is necessary to efficiently produce in vitro cell types that can be used in the clinic to replace tissue lost or altered during the course of a disease. Designing better protocols to treat some of the most serious pancreatic illnesses also requires better knowledge of processes that preserve the integrity and proper function of the mature exocrine pancreas. The studies proposed in this application are directed towards achieving these goals, as well as generating valuable tools that can help other researchers in the field.
