Research & Publications
I am investigating the role of stem and progenitor cells in the liver during normal development and in response to liver injury. The liver's remarkable capacity for regeneration after injury suggests that a better understanding of these phenomena will lead to novel cell therapy and regenerative medicine approaches to acute and chronic liver disease. Under some conditions, cells arising from the bone marrow may also contribute to liver regeneration.
The Y chromosome (pink dots) colocalizes with HNF-1 (green nuclei). Nuclei are counterstained with DAPI (blue). The recipient mouse had a homozygous targeted mutation in the Fumaryl acetoacetate hydrolase (FAH) gene, which models the human liver disease, Hereditary Tyrosinemia. Transplantation of normal bone marrow results in extensive repopulation of normal hepatocytes in the tyrosinemic liver. The presence of two or more Y chromosomes in some hepatocytes is consistent with the normal phenomenon of hepatocyte polyploidy.
Ongoing studies will address the issue of whether stable in vivo fusion of cells of hematopoietic origin, such as Kupffer cells, with injured hepatocytes always accounts for the apparent developmental "plasticity" of bone marrow-derived cells.
Hepatitis; Liver Cirrhosis; Pancreatic Diseases