Cellular homeostasis requires the regulated entry and exit of a multitude of compounds across the plasma membrane. Cells must take up specific amounts of nutrients, metabolic precursors, inorganic ions, signaling molecules, and other macromolecules, while also exporting signaling molecules, hormones, electrolytes, metabolic waste products and xenobiotics. Recent studies have described some of the genes involved in these transport processes; however, it is clear that many other genes and gene products remain to be identified and characterized.

       The major goal of our laboratory is to identify and characterize the membrane transport proteins that mediate elimination of the foreign chemicals. Such transporters are expressed not only at the major excretory organs, but are present in most epithelial and endothelial tissues, including the brain-brain barrier, choroid plexus, and exocrine and endocrine glands. Genetic defects in transporter expression are associated with human diseases such as Dubin-Johnson syndrome, Wilson’s disease, Cystic Fibrosis, Progressive Familial Intrahepatic Cholestasis, Zellweger syndrome, Adrenoleukodystrophy, Tangier’s disease, and multidrug resistance, and may also be involved in some neurodegenerative diseases.

       Our current studies are characterizing three transporter families: two families are involved in the elimination of organic compounds from blood (the OATP and OAT families), and the other is principally responsible for the export of organic anions from cells (the MRP, or multidrug resistance-associated protein family). We are also characterizing a novel polygenic transporter that was recently identified in our laboratory, the Organic Solute Transporter-alpha and beta (Ost-alpha/Ost-beta), and are particularly interested in the disposition of compounds that are conjugated with the tripeptide glutathione (GSH), a major cellular antioxidant.

       In experiments performed each summer at the NIEHS Center for Membrane Toxicity Studies, Mount Desert Island Biological Laboratory, near Bar Harbor, Maine, we are examining the evolution of membrane transport proteins, and the mechanisms by which toxic chemicals interfere in plasma membrane functions.

Cernichiari E, Myers GJ, Ballatori N, Zareba G, Vyas J, Clarkson T. 2007. The biological monitoring of prenatal exposure to methylmercury. Neurotoxicology. Feb 23; [Epub ahead of print]

Hammond CL, Marchan R, Krance SM, Ballatori N. 2007. Glutathione export during apoptosis requires functional multidrug resistance-associated proteins. J Biol Chem. Mar 20; [Epub ahead of print]

Tradtrantip L, Piyachaturawat P, Soroka C, Harry K, Mennone A, Mahagita C, Ballatori N, Boyer JL. 2007. Phloracetophenone-Induced Choleresis in Rats is Mediated Through Mrp2. Am J Physiol Gastrointest Liver Physiol. Mar 15; [Epub ahead of print]

Meier-Abt F, Hammann-Hanni A, Stieger B, Ballatori N, Boyer JL. 2007. The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver. Toxicol Appl Pharmacol. Feb 1;218(3):274-279.

Mahagita C, Tanphichai K, Suksamrarn A, Ballatori N, Piyachaturawat P. 2006. 4-Hydroxyacetophenone-induced choleresis in rats is mediated by the Mrp2-dependent biliary secretion of its glucuronide conjugate. Pharm Res. Nov;23(11):2603-2610.

Ballatori, N. and M.S. Madejczyk. Transport of nonessential metals across mammalian cell membranes. 2006. Topics in Current Genetics 14:455-483.

Ballatori N, Henson JH, Seward DJ, Cai SY, Runnegar M, Fricker G, Miller DS, Boyer JL. 2006. Retention of structural and functional polarity in cultured skate hepatocytes undergoing in vitro morphogenesis. Comp Biochem Physiol B Biochem Mol Biol. Jun;144(2):167-179.

Halpern MD, Holubec H, Saunders TA, Dvorak K, Clark JA, Doelle SM, Ballatori N, Dvorak B. 2006. Bile acids induce ileal damage during experimental necrotizing enterocolitis. Gastroenterology. Feb;130(2):359-372.

Boyer JL, Trauner M, Mennone A, Soroka CJ, Cai SY, Moustafa T, Zollner G, Lee JY, Ballatori N. 2006. Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents. Am J Physiol Gastrointest Liver Physiol. Jun;290(6):G1124-1130.

Ballatori N, Christian WV, Lee JY, Dawson PA, Soroka CJ, Boyer JL, Madejczyk MS, Li N. 2005. OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Hepatology. Dec;42(6):1270-1279.

Ballatori N. 2005. Biology of a novel organic solute and steroid transporter, OSTalpha-OSTbeta. Exp Biol Med (Maywood). Nov;230(10):689-698. Review

Ballatori N, Hammond CL, Cunningham JB, Krance SM, Marchan R. 2005. Molecular mechanisms of reduced glutathione transport: role of the MRP/CFTR/ABCC and OATP/SLC21A families of membrane proteins. Toxicol Appl Pharmacol. May 1;204(3):238-255. Review.

Dawson PA, Hubbert M, Haywood J, Craddock AL, Zerangue N, Christian WV, Ballatori N. 2005. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. J Biol Chem. Feb 25;280(8):6960-6968.

Hammond CL, Madejczyk MS, and Ballatori N. 2004. Activation of plasma membrane reduced glutathione transport in death receptor apoptosis of HepG2 cells. Toxicol Appl Pharmacol. Feb 15;195(1):12-22

Elferink RO, Ottenhoff R, Fricker G, Seward DJ, Ballatori N, and Boyer J. 2004. Lack of biliary lipid excretion in the little skate, Raja erinacea, indicates the absence of functional Mdr2, Abcg5, and Abcg8 transporters. Am J Physiol Gastrointest Liver Physiol. May;286(5):G762-8. Epub 2003 Dec 30.

Seward, D.J., A.S. Koh, J.L. Boyer, and N. Ballatori. 2003. Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha -OSTbeta. J. Biol. Chem. 278:27473-27482.

Barlow, B.K., M.J. Thiruchelvam, L. Bennice, D.A. Cory-Slechta, N. Ballatori, and E.K. Richfield. 2003. Increased synaptosomal dopamine content and brain concentration of paraquat produced by selective dithiocarbamates. J. Neurochem. 85:1075-1086.

Lee, T.K., A.S. Koh, Z. Cui, R.H. Pierce, and N. Ballatori. 2003. N-Glycosylation controls functional activity of Oatp1, an organic anion transporter. Am. J. Physiol. 285:G371-G381.

Ballatori, N., J.L. Boyer and J.C. Rockett. 2003. Exploiting genome data to understand the function, regulation and evolutionary origins of toxicologically relevant genes. Environ. Health Persp. - Toxicogenomics 111:61-65.

Cai SY, Soroka CJ, Ballatori N, and Boyer JL. 2003. Molecular characterization of a multidrug resistance-associated protein, Mrp2, from the little skate. Am J Physiol Regul Integr Comp Physiol. Jan;284(1):R125-R130