During liver regeneration, quiescent hepatocytes reenter the cell cycle, proliferate and repopulate the diseased liver. This process is observed in many forms of acute liver injury specifically those caused by viruses, toxins and trauma. Therefore, prognosis in acute liver failure often depends on the ability of proliferation to outlast liver cell necrosis. The long-term objective of the studies outlined here is to use recent knowledge of events that regulate exit from quiescence to identify liver specific targets in the initiation of liver regeneration.
The first aim of the study is to evaluate for novel cyclin dependent kinase activities that regulate the transition from quiescence to active cell cycling. We believe that cyclin dependent kinase activities that precede the canonical G1 cyclins are important in transiting from G0 to G1 during the regenerative process.
The second aim of the study is to design a siRNA based screen that targets genes up regulated in the priming phase of liver regeneration. The goal is to identify genes whose products are necessary for cycle progression. Our hope is to identify physiologically relevant molecules that can be therapeutic targets for enhancement of liver proliferation. A cell based assay using H35 rat liver cell line, which can undergo the transition from quiescence to cell cycle reentry, will be used for both lines of inquiry. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK073236-01A1
Application #
7142463
Study Section
Hepatobiliary Pathophysiology Study Section (HBPP)
Program Officer
Serrano, Jose
Project Start
2006-07-10
Project End
2008-06-30
Budget Start
2006-07-10
Budget End
2007-06-30
Support Year
1
Fiscal Year
2006
Total Cost
$201,875
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Liu, Zhilin; Ukomadu, Chinweike (2008) Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant. Biochem Biophys Res Commun 365:729-34