Acute and chronic pancreatitis are major health-care problems in the United States causing years of pain and disability. Despite the impact of these diseases, mystery surrounds many of the predisposing causes and early molecular events. Furthermore, the devastating effects of acute pancreatitis and chronic pancreatitis, once established, cannot be reversed. We believe that in the future, advances in the treatment of pancreatic disease rest in the early identification of at-risk individuals as well as in the prevention of limitation of pancreatic injury. Thus, the goal of our program is to determine the molecular mechanisms that predispose to acute and chronic pancreatitis and to identify targets for disrupting pathophysiological processes. We believe that effective preemptive actions will prevent or limit pancreatic injury and thus, result in the reduction of he incidence and severity of acute and chronic pancreatitis. To understand the mechanisms of pancreatitis we will identify previously uncharacterized hereditary pancreatitis families and investigate several striking features of this disease including incomplete penetrance and the mechanisms causing pancreatitis with trypsinogen RR117H and N21I mutations. Answering this question may provide insight into the pathophysiology of acute and chronic pancreatitis and identify targets for new therapies, and help identify individuals at risk through genetic testing.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK054709-01
Application #
2726490
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Serrano, Jose
Project Start
1999-04-01
Project End
2002-11-30
Budget Start
1999-04-01
Budget End
1999-11-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Whitcomb, David C (2015) Innovation and hard work: The 2015 George E. Palade Medal Award Lecture. Pancreatology 15:611-5
Mounzer, Rawad; Whitcomb, David C (2013) Genetics of acute and chronic pancreatitis. Curr Opin Gastroenterol 29:544-51
Whitcomb, David C (2013) Genetic risk factors for pancreatic disorders. Gastroenterology 144:1292-302
Larusch, J; Whitcomb, D C (2012) Genetics of pancreatitis with a focus on the pancreatic ducts. Minerva Gastroenterol Dietol 58:299-308
Whitcomb, David C; LaRusch, Jessica; Krasinskas, Alyssa M et al. (2012) Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis. Nat Genet 44:1349-54
Solomon, Sheila; Whitcomb, David C (2012) Genetics of pancreatitis: an update for clinicians and genetic counselors. Curr Gastroenterol Rep 14:112-7
Whitcomb, David C (2012) What is personalized medicine and what should it replace? Nat Rev Gastroenterol Hepatol 9:418-24
Whitcomb, David C (2012) Genetics of alcoholic and nonalcoholic pancreatitis. Curr Opin Gastroenterol 28:501-6
LaRusch, Jessica; Barmada, M Michael; Solomon, Shiela et al. (2012) Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred. JOP 13:258-62
Schneider, Alexander; Larusch, Jessica; Sun, Xiumei et al. (2011) Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis. Gastroenterology 140:162-71

Showing the most recent 10 out of 49 publications