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.

Marchan R, Hammond CL, Ballatori N. Multidrug resistance-associated protein 1 as a major mediator of basal and apoptotic glutathione release. Biochim Biophys Acta. 2008 Jun 21. [Epub ahead of print]

Ballatori N, Fang F, Christian WV, Li N, Hammond CL. Ost{alpha}-Ost{beta} is required for bile acid and conjugated steroid disposition in the intestine, kidney, and liver. Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G179-186.

Hwang JH, Parton A, Czechanski A, Ballatori N, Barnes D. Arachidonic acid-induced expression of the organic solute and steroid transporter-beta (Ost-beta) in a cartilaginous fish cell line. Comp Biochem Physiol C Toxicol Pharmacol. 2008 Jul;148(1):39-47

Aremu DA, Madejczyk MS, Ballatori N. N-acetylcysteine as a potential antidote and biomonitoring agent of methylmercury exposure. Environ Health Perspect. 2008 Jan;116(1):26-31.

Li N, Cui Z, Fang F, Lee JY, Ballatori N. Heterodimerization, trafficking and membrane topology of the two proteins, Ost alpha and Ost beta, that constitute the organic solute and steroid transporter. Biochem J. 2007 Nov 1;407(3):363-372.

Cai SY, Xiong L, Wray CG, Ballatori N, Boyer JL. The farnesoid X receptor FXRalpha/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution. Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1400-1409.

Clarkson TW, Vyas JB, Ballatori N. Mechanisms of mercury disposition in the body. Am J Ind Med. 2007 Oct;50(10):757-764. Review.

Madejczyk MS, Aremu DA, Simmons-Willis TA, Clarkson TW, Ballatori N. Accelerated urinary excretion of methylmercury following administration of its antidote N-acetylcysteine requires Mrp2/Abcc2, the apical multidrug resistance-associated protein. J Pharmacol Exp Ther. 2007 Jul;322(1):378-384.>

Mahagita C, Grassl SM, Piyachaturawat P, Ballatori N. Human organic anion transporter 1B1 and 1B3 function as bidirectional carriers and do not mediate GSH-bile acid cotransport. Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G271-278.

Cernichiari E, Myers GJ, Ballatori N, Zareba G, Vyas J, Clarkson T. 2007. The biological monitoring of prenatal exposure to methylmercury. Neurotoxicology. 2007 Sep;28(5):1015-1022

Hammond CL, Marchan R, Krance SM, Ballatori N. 2007. Glutathione export during apoptosis requires functional multidrug resistance-associated proteins. J Biol Chem. 2007 May 11;282(19):14337-47.

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. 2007 Jul;293(1):G66-74

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.