Protease enzymology research group
Dr. András Szabó – research fellow
Prof. Dr. József Tőzsér – full professor, head of department
Csilla Farkas – MSc student
Contact
András Szabó: andrasszabo@med.unideb.hu
Research topics
Our laboratory focuses on the investigation of human pancreatic digestive enzymes, proteases and their inhibitors in healthy and pathological conditions. The proteases are produced by pancreatic acinar cells as inactive precursors, secreted into the gut where they are activated to fulfill their digestive functions. The activation of these proteases is tightly regulated, as premature activation of these enzymes may lead to the auto-digestion of the pancreas, and the development of chronic pancreatitis. Chronic pancreatitis is a progressive inflammatory disease of the pancreas characterized by histological changes of the pancreatic parenchyma and gradual loss of pancreatic function. Chronic pancreatitis; particularly in the pediatric population, often develops on the basis of genetic susceptibility. Mutations in genetic risk factors appear to cause chronic pancreatitis through two independent pathological pathways which involve either trypsin activation or protein misfolding. Mutations in risk genes such as PRSS1 (cationic trypsin), SPINK1 (serine protease inhibitor Kazal-type 1) and CTRC (chymotrypsin C) may increase intra-pancreatic trypsin activation. On the other hand, CPA1 (carboxypeptidase A1) mutations and a small number of PRSS1 mutations may result in misfolding, intracellular retention, degradation and endoplasmic reticulum (ER) stress.
One of our main goals is to study the protective mechanisms of the pancreas which inhibit early protease activation. Our further aim is the characterization of mutant proteases with biochemical and molecular methods to discover new and independent pathomechanisms by which mutations may lead to the development of chronic pancreatitis.
