Mechanisms and Treatment Development for Pancreatitis Resulting from Alcohol Abuse and Smoking
Abstract
Pancreatitis and the progressive and chronic forms of the disease cause significant patient suffering, for which there are currently no approved treatments or preventative measures. The proposed work has the potential to make significant gains in understanding the risk factors and behaviors that contribute to pancreatic diseases and developing lifestyle recommendations for prevention and potential therapeutics for treatment. Discovering preventative strategies and potential treatments for alcoholic pancreatitis is of particular importance for military personnel and Veterans, as they suffer disproportionately from pancreatitis compared to the general population and engage more frequently in the behaviors (alcohol use and smoking) that can increase risk of pancreatitis. There are a variety of factors that contribute to pancreatitis development, including genetic and environmental, and disease severity can be varied. Acute pancreatitis is an isolated event caused by sudden inflammation of the pancreas that causes severe abdominal pain and usually requires hospitalization. Though an isolated incident in some, acute pancreatitis can sensitize a patient to develop recurrent pancreatitis, chronic pancreatitis, pancreatogenic diabetes, referred to as Type 3c diabetes, and, ultimately, pancreatic cancer. In all these forms, pancreatitis is a leading cause of hospitalizations for gastrointestinal disorders and represents a substantial cost of more than 2 billion dollars per year in the U.S. Consistent with the goals of the Fiscal Year 2018 Peer Reviewed Medical Research Program Pancreatitis Topic Area of Interest, the proposed program of research aims to prevent the progression of pancreatitis to a chronic state and determine how lifestyle factors, such as alcohol use and smoking, influence disease progression and the underlying mechanisms of damage that perpetuate and worsen disease. Researchers at Cedars-Sinai Medical Center, Stanford Medical Center, the Public Health Institute, University of Pittsburgh, University of California, Los Angeles, University of New South Wales, Veterans Administration Greater Los Angeles Healthcare System, and VA Pittsburgh Healthcare System will combine efforts across four projects aimed at gaining a better understanding of the risk factors and behaviors that contribute to pancreatic diseases, the molecular mechanisms that underlie the effects of alcohol and smoking on disease risk and progression, and the molecular steps in disease progression that can be targeted by combinations of agents to halt and reverse the pancreatitis disease continuum. In Project 1, Drs. Jeon and Yadav will perform clinical research, referred to as a case-crossover study, to determine the associations between the patterns of drinking alcoholic beverages and smoking with episodes of pancreatitis. With expertise in population studies of gastroenterology, pancreatology, and alcohol research that can be translated from bench to bedside, this multidisciplinary project has the potential to identify triggers of pancreatitis that can be further studied in the other projects and used as a basis for updating lifestyle recommendations for patients with pancreatitis. This study will also provide human samples for investigation in Projects 2-4 to validate findings in the animal models and to suggest treatments that can be first tested in the animal models. In Project 2, Drs. Lugea, Gukovskaya, and Pandol will study human samples and animal models to determine the effects of alcohol and smoking on the cells of the pancreas and substructures within those cells. In Project 3, Drs. Habtezion and Apte will use human samples and animal models to determine the involvement of the immune system and inflammatory responses in acute and chronic pancreatitis and test potential therapeutics that may stop or reverse disease progression. In Project 4, Drs. Piplani, Pandol, and Gottlieb will use animal models and human samples to fu
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910888
Entities
People
- Stephen J Pandol
Organizations
- Cedars-Sinai Medical Center
- United States Army