This application to join the Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreas Cancer (CSCPDPC), seeks to examine the role of the immune system and of hormonal factors in chronic pancreatitis and its relationship to the development of diabetes and pancreas cancer. Our pre-clinical immunological studies suggest a pivotal role for macrophages, cytokines and stellate cells in predicting the development of fibrosis. Our pre-clinical hormonal studies focus on neuromedin U (NMU), which is a neuropeptide with an inhibitory effect on insulin secretion. It is also of interest for its potentil effect on macrophages and cytokines and its role in nociception. These observations may provide further insight into the natural history of chronic pancreatitis, and mechanisms for understanding the development of diabetes in the context of pancreas cancer. In response to this RFA, we have formed a strong scientific team with broad complementary expertise in clinical pancreatitis, immunology, and developmental biology. Our proposal is highly responsive to the RFA in several specific ways. (1) As a Clinical Center, we have the experience and capacity to develop and execute standardized multi-center protocols for enrolling cohorts of patients with chronic pancreatitis, diabetes and pancreas cancer. In this proposal, we specifically delineate a protocol for a prospective longitudinal cohort of patients with chronic pancreatitis accompanied with an annotated bio-repository of blood, urine, stool, and secretin stimulated pancreas fluid. We also have available 2 repositories of blood; one for patients with pancreatitis and the other of pancreas cancer, that are available for sharing with the consortium to support retrospective studies. (2) We will develop and validate cytokine profiles that may facilitate diagnosis of chronic pancreatitis and predict likelihood of associated complications. These may also lead to targets to support clinical trials to halt fibrosis. (3) We will develop and validate a serum-based assay of NMU that may help diagnose type 3c diabetes mellitus and pancreatic cancer-induced diabetes. This may lead to novel diagnostic tests to detect pancreatic cancer at earlier stages. The opportunity to further investigate and validate these novel observations in collaboration with other centers remains an exciting opportunity to accelerate research that could change chronic pancreatitis management and its associated complications of pancreatogenic diabetes and pancreas cancer development.

Public Health Relevance

Chronic pancreatitis has no cure, is associated with significant disability, and a higher risk of diabetes and pancreas cancer. By aligning our resources with several other clinical centers to form a consortium, we propose to pursue further studies regarding the role of the immune and hormonal system in chronic pancreatitis. These may lead to new insights into understanding how chronic pancreatitis progresses and complications develop including diabetes and pancreas cancer. New diagnostic tests and treatments can subsequently be developed and then validated by this consortium.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK108300-05
Application #
9783785
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Unalp-Arida, Aynur
Project Start
2015-09-28
Project End
2020-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Eibl, Guido; Cruz-Monserrate, Zobeida; Korc, Murray et al. (2018) Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer. J Acad Nutr Diet 118:555-567
Serrano, Jose; Andersen, Dana K; Forsmark, Christopher E et al. (2018) Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer: From Concept to Reality. Pancreas 47:1208-1212
Forsmark, Christopher E; Andersen, Dana K; Farrar, John T et al. (2018) Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis: Summary of the Working Group on Drug Development and Trials in Chronic Pancreatitis at the National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas 47:1200-1207
Fisher, William E; Cruz-Monserrate, Zobeida; McElhany, Amy L et al. (2018) Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas 47:1213-1221
Uc, Aliye; Perito, Emily R; Pohl, John F et al. (2018) INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort Study: Design and Rationale for INSPPIRE 2 From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas 47:1222-1228
Hart, Phil A; Andersen, Dana K; Mather, Kieren J et al. (2018) Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis Pancreas 47:1239-1243
Abbruzzese, James L; Andersen, Dana K; Borrebaeck, Carl A K et al. (2018) The Interface of Pancreatic Cancer With Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas 47:516-525
Lee, Linda S; Andersen, Dana K; Ashida, Reiko et al. (2017) EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-Summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop. Gastrointest Endosc 86:768-778
Park, Walter G; Habtezion, Aida (2017) Editors' Introduction to the Chronic Pancreatitis and Pancreatic Cysts Special Issue. Dig Dis Sci 62:1681-1682
Lee, Jonghyeob; Snyder, Emily R; Liu, Yinghua et al. (2017) Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells. Nat Commun 8:14686

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