Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Faculty
Faculty of Science
Faculty Sponsor
Dr. Lisa Porter
Proposal
Hepatocellular carcinoma (HCC) is the most prevalent primary cancer of the liver and one of the leading causes of cancer-related deaths worldwide. There are a multitude of risk factors that contribute to the development of HCC including viral infection, obesity, alcoholism, as well as non-alcoholic steatohepatitis (NASH). In the case of these chronic diseases and repeated injury, the liver continuously repairs itself to maintain its structural integrity, resulting in fibrosis, and in more serious cases, cirrhosis– major risk factors in the development of HCC. Men are 3-5x more likely to develop liver cancer than women; however, the exact mechanism for this remains undetermined. Previous work in our lab using a transgenic mouse model overexpressing the cyclin-like protein Spy1 showed an increased incidence of HCC and decrease in rates of fibrosis, suggesting a link between cell cycle regulation and progression to HCC. Spy1 binds and activates CDKs at the G1-S and G2-M checkpoints, leading to cell cycle progression independent of cyclin-based regulation. Using a methionine-choline deficient diet to induce NASH, the role of various cell cycle mediators will be investigated to uncover the link between cell cycle regulation and NASH disease progression. In addition, differences between female and male mouse responses to the diet with respect to cell cycle regulation will be analyzed. A better understanding of the relationship between cell cycle regulation and NASH disease progression in both female and male mouse models will help identify novel diagnostic markers and pathways of therapeutic importance in HCC.
Availability
March 29: 12-3pm , March 30: 12-2 , March 31: 12pm-3pm, April 1:12-3
The Role of Cell Cycle Mediators in the Progression of Non-alcoholic Steatohepatitis in Male and Female Murine Models
Hepatocellular carcinoma (HCC) is the most prevalent primary cancer of the liver and one of the leading causes of cancer-related deaths worldwide. There are a multitude of risk factors that contribute to the development of HCC including viral infection, obesity, alcoholism, as well as non-alcoholic steatohepatitis (NASH). In the case of these chronic diseases and repeated injury, the liver continuously repairs itself to maintain its structural integrity, resulting in fibrosis, and in more serious cases, cirrhosis– major risk factors in the development of HCC. Men are 3-5x more likely to develop liver cancer than women; however, the exact mechanism for this remains undetermined. Previous work in our lab using a transgenic mouse model overexpressing the cyclin-like protein Spy1 showed an increased incidence of HCC and decrease in rates of fibrosis, suggesting a link between cell cycle regulation and progression to HCC. Spy1 binds and activates CDKs at the G1-S and G2-M checkpoints, leading to cell cycle progression independent of cyclin-based regulation. Using a methionine-choline deficient diet to induce NASH, the role of various cell cycle mediators will be investigated to uncover the link between cell cycle regulation and NASH disease progression. In addition, differences between female and male mouse responses to the diet with respect to cell cycle regulation will be analyzed. A better understanding of the relationship between cell cycle regulation and NASH disease progression in both female and male mouse models will help identify novel diagnostic markers and pathways of therapeutic importance in HCC.