Thesis supervisor: Péter Hegyi
Location of studies (in Hungarian): PTE ÁOK Pécs, Szigeti u. 12. Abbreviation of location of studies: ÁOK
Description of the research topic:
Most studies on the cellular mechanisms of AP have focused on the acinar cells and little is known about the role of pancreatic ductal epithelial cells (PDEC) in the disease. However, recent studies, including those from our group, indicate that PDEC are intimately involved in the pathogenesis of AP: (i) bile acids, well-known imitators of AP, impair pancreatic ductal function (Gut, 2008 57:1102-12 és Gut, 2011 60:361-9), (ii) compromised ductal fluid and bicarbonate secretion can increase patient risk to AP (Am J Gastro, 2010, 105:2119-20), (iii) mitochondrial injury and ATP depletion is one of the key aspects of ductal damage (Gut, 2010 Sept 28. [Epub ahead of print] and Gut 2011 60:136-8) and (iv) trypsin, the protease long recognized to be involved in the pathogenesis of AP, inhibits bicarbonate secretion (preliminary data). These recent observations strongly suggest that restoration of pancreatic ductal bicarbonate and fluid secretion may have therapeutic benefits in AP. In this project we propose both in vitro and in vivo experiments using novel cell physiological and biochemical techniques (i) to understand the development of ductal damage in response to active trypsin and (ii) to find new therapeutic targets and treatment possibilities which may restore ductal function. In this project we propose to employ both in vitro and in vivo cutting-edge cell physiological and biochemical techniques to (i) understand the development of ductal damage, especially the inhibitory effects of trypsin at the cellular level and (ii) find new therapeutic targets and develop novel treatment possibilities to (which may) restore ductal function. Acute pancreatitis (AP) is an inflammatory disorder of the pancreas with an unacceptable high mortality (5-10%) and with no specific pharmacological treatment. Therefore, pathophysiological studies aiming to understand the development of the disease are crucially important. By the end of this project, hopefully we will announce a colloidal ATP delivery system for pancreatic energy supply that can protect the pancreatic ductal (and probably acinar) cells from cell death. The results of this project may open up the possibility of pharmacological therapy of acute pancreatitis for the first time, leading to reduced morbidity and mortality.
Number of students who can be accepted: 1
Deadline for application: 2022-05-20
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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