Liver Function Laboratory

Liver Function Studies:

The long-term objective of the liver function studies at Tufts Cummings School of Veterinary Medicine is to clearly define cellular mechanisms involved in hepatic solute transport and bile formation, which are important functions of the liver. Such an understanding should allow us to devise pharmacological means to stimulate blood to bile solute transport in cholestastic disorders, i.e., the various liver diseases associated with decreased bile formation.

The goal of our current NIH-funded studies is to define the role of various cellular mediators in blood to bile transport of bile acids. Presently, we are studying the regulatory roles of various kinases and phosphatase. In cholestasis, solutes (endogenous and exogenous) destined for bile accumulate either in the liver or blood. This can result in jaundice and hepatocellular damage in the case of bilirubin, and toxic bile acids accumulation in the blood and liver respectively.

Hypotheses Being Tested:

1. The short term regulation of Na+/TC cotransport by cAMP involves translocation of bile acid transporter to the sinusoidal (blood side of liver cells) membrane. The translocation requires P13K/PKB activity, involves vesicular transport, and is facilitated by dephosphorylation, a process that is stimulated by PP2A and PP2B and inhibited by MAPK.
2. PI3K and MAPK stimulate canalicular (bile side of liver cells) ATP-dependent bile acid transport by translocating spgp to the canalicular membrane.

Our researchers are using standard molecular and cell biological techniques (i.e., transfection, phosphorylation, immunoblotting, immunoprecipitaion). The models are experimental and include isolated perfused rat livers, rat hepatocytes, plasma membrane vesicles and hepatoma cells.

Personnel:

• Dr. Sawkat Anwer, DMVH, PhD, Distinguished Professor, Associate Dean for Research
• Dr. Christopher Schonhoff, PhD, Research Assistant Professor
• Holly Jameson, MS, Research Coordinator
• Ariel Hobson, Research Technician

Facility/Laboratory Specifications:

• Scintillation counter
• Ultracentrifuge
• Fluorescent/UV/visible spectrophotometers,
• Cell culture facility
• Gel electrophoresis (1D and 2D) apparatus.
• Fluorescent Microscopy

Collaborating Institutions:

• Yale University School of Medicine
• University of California at San Diego Medical School
• Mount Sinai Medical School, New York
• University of Zurich Medical School, Switzerland