Defining epigenetic alterations in liver cancer at single cell resolution

Hepatocellular carcinoma (HCC) is the most common liver cancer and is predicted to become the third most prevalent cause of cancer mortality by 2030. Therapeutic options are limited and those that are available have inadequate efficacy. HCC tumors share similarities with developing liver cells and express genes important for liver development. However, the genetic basis of these similarities still remains unclear. Many liver cancers have mutations in genes that regulate chromatin structure, however how chromatin is altered in HCC and how this contributes to abnormal gene expression have yet to be examined. Our study will utilize advanced single-cell genomic methods to identify changes in chromatin structure in HCC tumors and compare them to adjacent liver tissue and normal livers. This will lead to the identification regulatory DNA sequences and their gene targets associated with HCC progression. We will investigate the function of these DNA sequences and their gene targets in the context liver development using a model of human liver development derived from stem cells. Our study will result in a better understand the molecular underpinnings driving HCC and facilitate discovery of improved therapeutic targets.