Our lab focuses on elucidating the functions of microRNAs and the factors involved in DNA methylation/hydroxymethylation in liver biology. We also examine the consequence of their deregulation in liver disease, such as alcoholic and nonalcoholic fatty liver disease, drug-induced liver toxicity and liver cancer. We utilize primary hepatocytes, cell culture and mouse models, as well as diseased liver tissues from patients, to better understand the role of these factors in liver biology and disease processes. Our goal is to develop therapies for various liver diseases including hepatocellular cancer (HCC).
A major accomplishment of our lab is the generation of conditional miR-122 knockout mice. miR-122 is a pleiotropic abundant microRNA in the liver whose expression is downregulated in many liver diseases, including HCC. Its suppression in HCC patients is a marker of bad prognosis and poor survival. Progressive development of spontaneous steatohepatitis, fibrosis and HCC in miR-122 knockout mice not only established miR-122 as a tumor-suppressor miRNA but also suggested its role as a therapeutic agent against HCC. Indeed, delivery of miR-122 using an AAV vector or nanoparticles reduced HCC development in different mouse models. Our goal is to use this knockout mouse model that recapitulates different stages of human HCC to gain mechanistic insight and test novel therapeutics to gather preclinical data before their clinical trials in human patients. Additionally, we are trying to develop nanoparticles for targeted delivery of microRNAs to liver tumors in collaboration with nanotechnologists at Ohio State.
Alo Ray, PhD
Huban Kutay, PhD