Thesis topic proposal
Balázs Németh
Genetics of pancreatitis


Institute: University of Szeged
theoretical medicine
Theoretical Medicine Doctoral School

Thesis supervisor: Balázs Németh
Location of studies (in Hungarian): Universitat of Szeged, Facultas of medicine First Deparment of Internal Medicine
Abbreviation of location of studies: In1st

Description of the research topic:

Early activation of trypsinogen inside the pancreas is a key molecular mechanism in the pathogenesis of pancreatitis that results in self-digestion and local inflammation of the organ. Recurrent acute inflammatory episodes of the pancreas lead to development of chronic pancreatitis. The desease irreversibly destroys structure and function of the pancreas and results in permanent endocrine and exocrine insufficiency. Pancreatitis is a multifactorial disease. Among other susceptibility factors genetic alterations also play a role in the pathogenesis. Pathogenic mutations may lead to the development of pancreatitis via trypsin-dependent (PRSS1, CTRC, SPINK1), misfolding-dependent (CPA1, CEL) or ductal dysfunction (CFTR) pathways. Chymotrypsinogen C (CTRC) plays a significant role in regulating trypsinogen activation. Loss-of-function mutations in the CTRC gene encoding chymotrypsinogen C impair the catalytic activity or the expression of the enzyme. Therefore, as a result of certain CTRC mutations, trypsinogen activation increase inside the pancreas. Impaired expression of CTRC might be caused by variants in the 5' upstream region.Identifying and functional analysis of variants in the 5' upstream region of CTRC could help us to understand better the molecular mechanism of pancreatitis.

Required language skills: english
Number of students who can be accepted: 1

Deadline for application: 2019-12-31

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