The impact of Cyclin E1 in alcohol-induced organ disease and carcinogenesis within the Gut-liver axis

• Applicant: Dr. Yulia Nevzorova, Ph.D.
• Subject Area: Gastroenterology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 334239546

The impaired interaction between gut and liver is a frequent cause of various liver diseases. Alterations in the permeability of the intestinal epithelium lead to the intensive passage of intestinal microflora followed by hepatic inflammation or end-stage carcinogenesis. In previous work, it was shown that inhibition of the cell cycle mediator Cyclin E1 has a protective effect in an established mouse model of liver tumorigenesis. However, the absence of Cyclin E1 caused increased liver and gut epithelium injury after chronic alcohol exposure. The main aim of the current proposal is to elucidate the function of Cyclin E1 in the alcohol-induced tumorigenesis in the intestine and in the liver. To this end, an in-depth analysis of the consequences of complete Cyclin E1 depletion in mice after chronic alcohol exposure will be performed in the gut-liver axis, and effector cells will be identified. Additionally, using murine models, it will be examined whether inhibition of Cyclin E1 is protective against the development of alcohol-induced liver or colon cancer. Finally, the clinical translationality of our preclinical research will be explored by determining the prevalence of Cyclin E disorders in patients with alcohol-induced liver and colon cancer. In summary, this study is of utmost interest since it will be able to unveil whether the inhibition of Cyclin E1 provides a novel therapeutic option for the treatment of alcohol-related cancers.

• DFG Programme: Research Grants