Mount Desert Island Biological Lab

Center for Membrane Toxicity Studies

James L Boyer, M.D.
james.boyer@yale.edu
http://www.mdibl.org/

Project Description

Since 1985, the goal of the Center for Membrane Toxicity Studies, located at the Mt. Desert Island Biological Laboratory (MDIBL) in Salisbury Cove, Maine has been to involve a group of internationally recognized scientists, who are experts in mechanisms of epithelial transport, to study the biological effects of environmental pollutants on cell and membrane transport functions. The focus of these efforts has been to elucidate the mechanisms of toxicity and pathways of excretion of environmental toxicants at the cellular and molecular level using novel aquatic models developed at this laboratory. This Center grant facilitates this effort by providing: a) administrative and research facility support, b) pilot-feasibility grants to attract new investigators to work on Center goals, and c) community outreach and educational programs that include student education programs (minority and local high school students), and shared activities with environmental groups in local high schools. In addition to the Administrative Core, the Center is composed of 5 Facility Cores: an Animal Core, Instrumentation Core, Cell Isolation, Culture and Organ Perfusion Core, an Imaging Core, and a newly formed Bioinformatics Core. The Research Base of the Center includes a core group of 21 investigators (Bain, Baldwin, Ballatori, Barnes, Boyer, Callard, Dranoff, Forbush, Forrest, Fricker, Henson, Kinne, Kullman, Mattingly, Miller, Renfro, Riordan, Sate, Stanton, Villalobos and Xiao) who focus on two common research themes: 1) signal transduction and ion transport, and 2) xenobiotic transport and excretion. Investigators in the Pilot Feasibility Program also contribute to these research themes. While the research activities of this Center were traditionally seasonal, the Center's research base is now increasingly a year-round scientific activity both at the MDIBL and at the investigators' home institutions.

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Project Highlights

1) Ballatori and Colleagues demonstrated that the novel heteromeric organic solute transporter (OSTalpha-OSTbeta), that they had originally cloned from the liver of a marine Elasmobranch, is expressed in human intestine, kidney and liver and transports bile acids and other steroid derived solutes such as DHEAS by facilitated diffusion. This transporter is also believed to be the mechanism by which bile acids are transferred from the terminal ileum to the portal circulation , completing the missing link in bile acid enterohepatic circulation. (Ballatori et al Hepatology 42:1270-1279, 2005)

2) Boyer and Ballatori further demonstrated that this novel solute transporter that is expressed on the basolateral membrane of the hepatocytes in human liver and other epithelia, is significantly up-regulated in cholestatic liver injury in human and rodents where it is part of an adaptive response in transporter expression in the liver to minimize the hepatic retention of toxic bile acids and other steroid related compounds. This process is highly regulated by the nuclear receptor, FXR. (Boyer et al AJP 290:G1124-G1130, 2006)

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