Exploring the Role of Spy1 in the Onset and Progression of Non-Alcoholic Fatty Liver Disease to Hepatocellular Carcinoma
Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Challenges Theme
Open Challenge
Faculty Sponsor
Dr. Lisa Porter, Dr. Bre-Anne Fifield
Proposal
Liver cancer is one of the leading causes of cancer death globally, of which 90% of cases are Hepatocellular Carcinoma (HCC). One risk factor of HCC is Non-Alcoholic Fatty Liver Disease (NAFLD), often triggered by sedentary lifestyle, poor diet, and obesity. Most cases of HCC are cirrhotic and can start from excess fat accumulation in NAFLD. Chronic fat can trigger inflammatory responses that damage cells, leading to the liver initiating a proliferative response to recover. However, over time the liver shifts to a fibrotic state to maintain structural integrity with low levels of proliferation, characteristic of Non-Alcoholic Steatohepatitis (NASH). As fibrosis becomes extensive, the liver becomes cirrhotic, and the environment increases HCC risk; however, 20% of HCC cases are non-cirrhotic arising directly from NAFLD. The atypical cyclin-like protein Spy1 is capable of binding to CDKs, increasing cell division and overriding checkpoints. Spy1 has been shown to have a role in cancers, including HCC. Previous research has shown that mice with overexpressed Spy1 in the liver develop NAFLD and HCC with decreased fibrosis, suggesting that elevation of Spy1 drives a proliferative response in the presence of cell damage, thus increasing HCC risk. To better understand the mechanisms that govern this response and the role of Spy1, this project examines NAFLD development in a transgenic mouse model driving Spy1 overexpression in the liver. This work may lead to the use of Spy1 as a potential drug target in the treatment of HCC.
Grand Challenges
Viable, Healthy and Safe Communities
Exploring the Role of Spy1 in the Onset and Progression of Non-Alcoholic Fatty Liver Disease to Hepatocellular Carcinoma
Liver cancer is one of the leading causes of cancer death globally, of which 90% of cases are Hepatocellular Carcinoma (HCC). One risk factor of HCC is Non-Alcoholic Fatty Liver Disease (NAFLD), often triggered by sedentary lifestyle, poor diet, and obesity. Most cases of HCC are cirrhotic and can start from excess fat accumulation in NAFLD. Chronic fat can trigger inflammatory responses that damage cells, leading to the liver initiating a proliferative response to recover. However, over time the liver shifts to a fibrotic state to maintain structural integrity with low levels of proliferation, characteristic of Non-Alcoholic Steatohepatitis (NASH). As fibrosis becomes extensive, the liver becomes cirrhotic, and the environment increases HCC risk; however, 20% of HCC cases are non-cirrhotic arising directly from NAFLD. The atypical cyclin-like protein Spy1 is capable of binding to CDKs, increasing cell division and overriding checkpoints. Spy1 has been shown to have a role in cancers, including HCC. Previous research has shown that mice with overexpressed Spy1 in the liver develop NAFLD and HCC with decreased fibrosis, suggesting that elevation of Spy1 drives a proliferative response in the presence of cell damage, thus increasing HCC risk. To better understand the mechanisms that govern this response and the role of Spy1, this project examines NAFLD development in a transgenic mouse model driving Spy1 overexpression in the liver. This work may lead to the use of Spy1 as a potential drug target in the treatment of HCC.