Andrew W. Duncan, PhD

Research in the Duncan lab focuses on liver development, homeostasis and regeneration. Polyploidy is a defining feature of the adult liver. Hepatocytes are either mononucleated or binucleated, and ploidy is determined by the number of nuclei per cell as well as the ploidy of each nucleus. Although hepatic polyploidy has been described for well over 100 years, the functional role of hepatic polyploidization is unclear. Dr. Duncan's lab recently showed that regenerating polyploid hepatocytes undergo specialized cell divisions to form aneuploid daughter cells, generating a high degree of genetic diversity within the liver. Moreover, in rodent models, chromosome-specific aneuploid hepatocytes were shown to play a specialized role in liver regeneration, promoting adaptation and resistance to different forms of chronic liver injury. Specific projects involve the following areas:

1. Identification of the molecular and cellular players that regulate aneuploidy/polyploidy is ongoing. The cell cycle in most normal mammalian cells is tightly regulated, prohibiting expansion of polyploid and/or aneuploid cells. Experiments examine the extent of hepatocyte-specific cell cycle regulation. Additionally, multiple types of cells coordinate the overall degree of polyploidy/aneuploidy in the liver. Studies are underway to determine how diverse cell types (including stem and progenitor cells) contribute to genetic diversity.
2. Current work investigates the function of aneuploid hepatocytes. Although aneuploidy in the liver is exceptionally high (>50% of hepatocytes), spontaneous liver cancer is very rare, suggesting that aneuploidy is not necessarily a predisposition for liver cancer. Recent data suggest that hepatic aneuploidy is actually beneficial, promoting adaptation to liver injury. We are actively developing new mouse models to explore "beneficial" and "pathological" adaptation mediated by aneuploid hepatocytes.
3. It is unknown how polyploid and aneuploid hepatocytes affect human liver disease. Studies are underway to determine how these cells contribute to pathogenesis and/or regeneration in a variety of liver diseases, including hepatocellular carcinoma and alcohol liver disease.

Dr. Duncan is a core faculty member in the McGowan Institute for Regenerative Medicine, a member of the University of Pittsburgh Cancer Institute, and he holds a secondary appointment in the Department of Bioengineering.

NIH Research

View Dr. 's NIH RePORT on nih.gov.