Functional analysis of CELA3A, CASR and SCTR mutations associated to chronic pancreatitis

• Applicant: Professor Dr. Heiko Witt, since 9/2023
• Subject Area: Nutritional Sciences
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 493957942

Chronic pancreatitis(CP) is an inflammatory condition of the pancreas that leads to exocrine or endocrine failure of the gland resulting in maldigestion or diabetes mellitus. In adults, alcohol abuse represents the major cause of CP, whereas in young patients inherited factors contribute mainly to the disease pathogenesis. Mutations in several genes have been associated to CP, most of these genes encode pancreatic digestive enzymes or enzyme inhibitors. Besides a disturbed intra-acinar balance of the pancreatic proteases-protease inhibitor system, defective calcium or bicarbonate homeostasis in ductal cells have been implicated in the pathogenesis. By genetic analysis of a well characterized pediatric chronic pancreatitis cohort from Germany, we identified mutations in one novel digestive enzymes, the chymotrypsin-like elastase 3A (CELA3A). In addition, very rare genetic variants in the calcium sensing receptor (CASR) and secretin receptor (SCTR) were over represented in the patient cohort. In this project, we will generate wild type and mutated recombinant proteins and will functionally analyze the effects of the mutations. Our studies will yield new insights into the pathogenesis of pancreatitis.

• DFG Programme: Research Grants
• International Connection: USA
• Cooperation Partner: Professor Miklos Sahin-Tóth
• Ehemalige Antragstellerin: Dr. Maren Ewers, until 8/2023