James Heslop, Ph.D.
Project: Molecular Basis of Human Hepatocyte Formation
Human liver development is incompletely understood. In part, this is due to the lack of available material to study the complex processes of differentiation, with most of our current understanding derived from mouse models. The recent establishment of protocols which allow for the scalable, reproducible and manipulatable differentiation of human induced pluripotent stem cells to hepatocyte-like cells has allowed for researchers to investigate human liver development in a dish. My projects focus on some of the earliest stages of differentiation, investigating the role of the GATA family of transcription factors during endoderm formation and the role of FGF signaling in hepatic specification. Both of these pathways have been shown to be essential for liver development, but the exact mechanisms which underlie their importance requires further investigation.
Ray Jui-Tung Liu, Ph.D.
Project: Identification of Small Molecules to Enhance the Formation of Hepatocytes From iPSCs
My project is using novel high throughput reporter assays to identify pathways that regulate hepatocyte maturation. We have generated human iPSC-lines that express secreted reporter proteins from genes that are characteristic of mature hepatocytes. We are using these cell lines to identify small molecules that impact the efficiency of differentiation. These studies will provide novel insight into the mechanisms that control hepatocyte maturation as well generate new procedures to efficiently produce human hepatocytes from stem cells.
Graduate Student PhD Program, Biomedical Science
Project: Identification of Novel Cellular Process that Control Hepatic Cell Fate
I joined the Duncan lab to gain experience in using induced pluripotent stem cells to study liver disease and development. Liver disease includes a broad range of disorders including those affecting metabolism, cholesterol production, and carbohydrate metabolism as well as infectious diseases, cirrhosis and fibrosis, and fatty liver disease such as NASH. In my project I have been using small molecule screens to identify pathways that affect the formation and function of hepatocytes. One pathway that I have focused on is that mediated by HSP90, which appears to be important for the expression of transcription factors that are key regulators of hepatic function. My project uses a wide variety of tools including drug screening, genome engineering, stem cell culture, and cell imaging as well a battery of molecular biology approaches.
James Corbett, Ph.D.