Andrew W. Duncan, PhD
Assistant Professor of Pathology
Dr. Duncan is member of the Division of Experimental Pathology and a member of the Cellular and Molecular Pathology Graduate Training Program. The Duncan Lab, which is part of the McGowan Institute for Regenerative Medicine, studies liver development and regeneration.
Bridgeside Point II, Suite 300
450 Technology Drive
Pittsburgh, PA 15219
Office Telephone: 412-624-5302
Lab Phone: 412-624-4622
- BS - University of North Carolina at Chapel Hill, 1996
- PhD - Duke University, 2005
- Postdoctoral Fellowship - Oregon Health and Science University (mentor, Markus Grompe), 2011
Research InterestsResearch 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:
- 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.
- 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.
- 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.
Selected PublicationsView Dr. Duncan's publications on PubMed
Duncan AW: Aneuploidy, polyploidy and ploidy reversal in the liver. Semin Cell Dev Biol (2013).
Duncan AW, Soto-Gutierrez A: Liver repopulation and regeneration: New approaches to old questions. Curr Opin Organ Transplant (2013).
Kurinna S, Stratton SA, Coban Z, Schumacher JM, Grompe M, Duncan AW, Barton MC: P53 regulates a mitotic transcription program and determines ploidy in normal mouse liver. Hepatology (2013).
Duncan AW, Hanlon Newell AE, Bi W, Finegold MJ, Olson SB, Beaudet AL, Grompe M: Aneuploidy as a mechanism for stress-induced liver adaptation. The Journal of clinical investigation (2012) 122(9):3307-3315.
Duncan AW, Hanlon Newell AE, Smith L, Wilson EM, Olson SB, Thayer MJ, Strom SC, Grompe M: Frequent aneuploidy among normal human hepatocytes. Gastroenterology (2012) 142(1):25-28.
Dorrell C, Erker L, Schug J, Kopp JL, Canaday PS, Fox AJ, Smirnova O, Duncan AW, Finegold MJ, Sander M, Kaestner KH et al: Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice. Genes & development (2011) 25(11):1193-1203.
Duncan AW, Taylor MH, Hickey RD, Hanlon Newell AE, Lenzi ML, Olson SB, Finegold MJ, Grompe M: The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature (2010) 467(7316):707-710.
Duncan AW, Dorrell C, Grompe M: Stem cells and liver regeneration. Gastroenterology (2009) 137(2):466-481.
Duncan AW, Hickey RD, Paulk NK, Culberson AJ, Olson SB, Finegold MJ, Grompe M: Ploidy reductions in murine fusion-derived hepatocytes. PLoS Genet (2009) 5(2):e1000385.
Duncan AW*, Rattis FM*, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N, Reya T: Integration of notch and wnt signaling in hematopoietic stem cell maintenance. Nat Immunol (2005) 6(3):314-322. *Equal authors.
Reya T*, Duncan AW*, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL: A role for wnt signalling in self-renewal of haematopoietic stem cells. Nature (2003) 423(6938):409-414. *Equal authors.
Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR, 3rd, Nusse R: Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature (2003) 423(6938):448-452.