Proinflammatory Epithelial Cells as a Therapeutic Target in Chronic Pancreatitis
Abstract
This proposal focuses on the topic area of pancreatitis, a prevalent and debilitating disease. Because it is often caused by alcohol use and Service personnel have an elevated rate of heavy drinking compared to the civilian population, pancreatitis is expected to have a particularly high impact on Service personnel, Veterans, and their beneficiaries. Moreover, pancreatitis is a risk factor for diabetes and pancreatic cancer. This proposal aims to understand – at a detailed molecular level – how normal cells within the pancreas change their behavior during pancreatic injury and how those changes promote persistent inflammation that changes pancreatitis from an acute to a chronic disease. Specifically, we hypothesize that chronic pancreatitis is perpetuated by cells that have undergone a process known as “metaplasia,” in which they lose their normal identity and adopt an alternative, abnormal identity. In this case, we are studying acinar cells, which ordinarily are dedicated to making the enzymes that digest food in the intestine, but which can undergo “acinar-ductal metaplasia” (ADM) to become more like duct cells, a less common cell that normally channels enzymes from the pancreas into the intestine. Based on published and unpublished studies, we hypothesize that cells undergoing ADM are responsible for the persistent injury that occurs in chronic pancreatitis and that by reversing the ADM process, we might reverse inflammation and injury. A potential route to this goal involves treatment with a protein, FGF21, which is being investigated as a therapeutic drug in other human diseases but has not been studied in chronic pancreatitis. In addition, we will better characterize the changes that occur in ADM, under the hypothesis that understanding these changes in detail will be required for progress against this untreatable disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810124
Entities
People
- Lewis Murtaugh
Organizations
- United States Army
- University of Utah