The plasma membrane is the key structural and functional barrier that establishes and maintains essential differences between the cell and its environment. This membrane controls the entry of nutrients, the exit of metabolic waste products and xenobiotics, it generates ion concentration gradients that regulate a multitude of processes, and it acts as a sensor of external signals, allowing the cell to respond to environmental stimuli.

       Research in our laboratory is focused on identifying and characterizing plasma membrane transport mechanisms for organic solutes, and on establishing the contribution of these transport processes to human diseases. We have used innovative models and approaches to elucidate fundamental mechanisms of plasma membrane transport of glutathione (GSH), glutathione S-conjugates, glutathione-metal complexes, and related compounds, and have defined the role of these transport mechanisms to hepatobiliary dysfunction. Our current studies relevant to GSH homeostasis are focused on identifying human gene products that contribute to GSH disposition, using a yeast (S. cerevisiae) functional complementation strategy recently developed in our laboratory.

       A major line of current investigation involves the study of the organic solute transporter-alpha and -beta (Ostα-Ostβ), a key transporter of bile acids and related molecules in the small intestine, kidney, and liver. This transporter was identified in our laboratory in 2001 using a novel functional expression cloning strategy in Xenopus laevis oocytes. Our studies to date of Ostα-Ostβ’s substrate specificity, transport mechanism, tissue distribution, subcellular localization, transcriptional regulation, as well as the phenotype of our recently generated Ostα-deficient mice indicate that Ostα-Ostβ is a critical intestinal bile acid transporter, and that it may thus contribute to intestinal absorption of dietary fats and vitamins, and to cholesterol, bile acid and lipid homeostasis in both health and disease. Studies are in progress to test these possibilities.

Soroka CJ, Velazquez H, Mennone A, Ballatori N, and Boyer JL. Ostα depletion protects liver from oral bile acid load. Am J Physiol Gastrointest Liver Physiol. 2011 Sep;301(3):G574-579. Epub 2011 Jun 30.

Ballatori N. Pleiotropic functions of the organic solute transporter Ostα-Ostβ. Dig Dis. 2011;29(1):13-7. Epub 2011 Jun 17.

Fang F, Christian WV, Gorman SG, Cui M, Huang J, Tieu K, Ballatori N. Neurosteroid transport by the organic solute transporter OSTα-OSTβ. J Neurochem. 2010 Jul 23. [Epub ahead of print].

Krance SM, Keng PC, Palis J, Ballatori N.Transient glutathione depletion determines terminal differentiation in HL-60 cells. Oxid Med Cell Longev. 2010 Jan-Feb;3(1):53-60.

Soroka CJ, Ballatori N,and Boyer JL. Organic solute transporter, OSTalpha-OSTbeta: its role in bile acid transport and cholestasis. Semin Liver Dis. 2010 May;30(2):178-185.

Shi S, Notenboom S, Dumont ME, and Ballatori N. Identification of human gene products containing Pro-Pro-x-Tyr (PY) motifs that enhance glutathione and endocytotic marker uptake in yeast. Cell Physiol Biochem. 2010;25(2-3):293-306.

Soroka CJ, Mennone A, Hagey LR, Ballatori N, and Boyer JL. Mouse organic solute transporter alpha deficiency enhances renal excretion of bile acids and attenuates cholestasis. Hepatology. 2010 Jan;51(1):181-190.

Cui M, Aras R, Christian WV, Rappold PM, Hatwar M, Panza J, Jackson-Lewis V, Javitch JA, Ballatori N, Przedborski S, Tieu K. The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway. Proc Natl Acad Sci U S A. 2009 May 12;106(19):8043-8048.

Ballatori N, Li N, Fang F, Boyer JL, Christian WV, Hammond CL. OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids. Front Biosci. 2009 Jan 1;14:2829-2844. Review.

Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009 Mar;390(3):191-214. Review.

Madejczyk MS, Boyer JL, Ballatori N. Hepatic uptake and biliary excretion of manganese in the little skate, Leucoraja erinacea. Comp Biochem Physiol C Toxicol Pharmacol. 2009 May;149(4):566-571.

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;1778(10):2413-2420.

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.