The first objective of the proposed application is to allow me the protected time for advanced training in clinical biostatistics, biomarker development, research study design, and epidemiology through completion of the Masters in Public Health program. After the rigorous training program outlined in this application, I will be in an excellent position to transition to an independent clinical research career. The second objective of the proposed studies is to develop a predictive model of disease progression in alcohol induced CP based on the expression of inflammatory and fibrogenic cytokines in the pancreatic secretome. The central hypothesis to be tested is that the 'Activation of inflammatory and fibrogenic pathways in the pancreas, as reflected in the cytokine profile in pancreatic secretions, predicts disease progression in CP and can be modulated by alcohol consumption, clinical and behavioral factors'. This hypothesis will be tested by two inter-related specific aims;(1) To develop a model using pancreatic juice pro-inflammatory cytokine levels as biomarkers to predict the development of organ failure and progression of disease stage in subjects with CP and, (2) specific behavioral factors including diet and patterns of alcohol consumption versus pancreatic juice cytokine profiles respectively. We expect to show that patterns of cytokine expression predict the development of exocrine failure, endocrine failure, pseudocyst and/or biliary stricture. We further expect to confirm that the more the number of outcomes, the greater the risk of mortality in subjects with CP. The rationale for these studies is that they will provide a way to capture outcomes in a quantifiable, yet clinically meaningful, way in CP which is not currently available. Moreover, it will allow development of a predictive model based on biomarkers in the pancreatic secretome that will allow quantification of the likelihood of developing one or more of the outcomes noted above. They will also set the stage for prospective validation of the model in subsequent years. By these innovative studies of biomarker discovery based on the pancreatic secretome in subjects with alcohol related CP, these studies are directly aligned with the priorities of the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
Chronic pancreatitis (CP) is a common and critical end-organ effect of alcoholism;there are no robust biomarkers to assess its severity and progression. This project aims at developing valid CP biomarkers to serve as surrogate clinical endpoints for better clinical management of and future therapeutic trials. This proposal is directly aligned with the strategic plan of National Institute of Alcohol Abuse and Alcoholism to develop biomarkers for alcohol related end organ damage.