Lauren Aleksunes, Pharm.D., Ph.D.
Department of Pharmacology and Toxicology
EOHSI, Rm 426
BS, University of Connecticut, Storrs, CT
Pharm.D., University of Connecticut, Storrs, CT
Ph.D., University of Connecticut, Storrs, CT
Post-Doc, University of Kansas Medical Center, Kansas City, KS
Our laboratory investigates how drug transporters protect against accumulation and toxicity of pharmaceuticals and environmental contaminants. Within the kidneys, apical efflux transporters enhance renal excretion of drugs and prevent nephrotoxicity. Similarly, these efflux pumps participate in maternal-fetal xenobiotic disposition, thereby protecting the developing fetus from toxicant exposure. Our laboratory utilizes state-of-the-art molecular biology, cell biology, in vivo animal, explant human tissue, and pharmacokinetic/pharmacodynamic approaches to study drug transporters. Attention is placed upon the molecular mechanisms underlying the regulation and function of MDR/PGP, MRP, and BCRP drug transporters. Of particular focus is the disposition of chemotherapeutic agents (such as cisplatin, Platinol®) as well as environmental contaminants.
Better understanding of how drug transporters protect against adverse events and environmental toxicant exposure will enhance prediction of drug-drug interactions as well as provide for the assessment of clinically-relevant single nucleotide gene polymorphisms.
Bircsak K, Richardson J, Aleksunes L (2013) Inhibition of human MDR1 and BCRP transporter ATPase activity by organochlorine and pyrethroid insecticides. J Bio and Mol Tox. Invited manuscript. In Press.
Yacavino L, Aleksunes L (2013) Down-regulation of brush border efflux transporter expression in the kidneys of pregnant mice. Drug Metab Disp. Invited manuscript. In Press.
Wen X, Donepudi A, Thomas P, Slitt A, King R, Aleksunes L (2013) Regulation of hepatic Phase-II metabolism in pregnant mice. J Pharmacol Exp Ther. In Press.
Gibson C, Richardson J, Aleksunes L (2013) Inflammatory regulation of ABC efflux transporter expression and function in microglia. J Pharmacol Exp Ther. In Press.
Aleksunes L, Yeager R, Wen X, Cui Y, Klaassen C (2013) Repression of hepatobiliary transporters and differential regulation of classic and alternative bile acid pathways in mice during pregnancy. Toxicol Sciences. In Press.
Aleksunes L, Klaassen C (2012) Coordinated regulation of hepatic phase-I, and –II drug metabolizing genes and transporters using AhR-, CAR-, PXR-, PPARalpha- and Nrf2-null mice. Drug Metab Disp. 40:1366-79.
Yacavino L, Aleksunes L (2012) Endocrine and metabolic regulation of renal drug transporters.
J Bio Mol Tox. 26:407-21.
Yacavino L, Aleksunes L (2012) Renal efflux transporter expression in pregnant mice with type 1 diabetes. Toxicology Letters. 211:304-11.
Kong B, Csanaky I, Aleksunes L, Patni M, Chen Q, Ma X, Jaeschke H, Weir S, Broward M, Klaassen C, Guo G (2012) Gender-specific reduction of hepatic Mrp2 expression by high-fat diet protects female mice from ANIT toxicity. Toxicol Applied Pharmacol. 261:189-95.
More V, Wen X, Thomas P, Aleksunes L, Slitt A (2012) Severe diabetes and leptin resistance causes differential hepatic and renal transporter expression in mice. Comp Hepatol. 11:1.
Zhang Y, Cheng X, Aleksunes L, Klaassen C (2012) Transcription factor-mediated regulation of carboxylesterase enzymes in livers of mice. Drug Metab Disp. 40:1191-7.
Cui JY, Aleksunes L, Tanaka Y, Fu Z, Guo Y, Lu H, Zhong X, Klaassen C (2012) Bile acids via FXR initiate the expression of major transporters involved in the enterohepatic circulation of bile acids in newborn mice. Amer J Physiol – Gastro Liver Physiol. 302:G979-96.
Cheng Y, Vapurcuyan A, Shahidullah M, Aleksunes L, Pelis R (2012) Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs. Drug Metab Disp.40: 617-24.
Donepudi A, Aleksunes L, Seeram N, Driscoll M, Slitt A (2012) The traditional Ayuverdic medicine, Eugenia Jambolana (Jamun Fruit) decreases liver inflammation, injury, and fibrosis during cholestasis. Liver International 32:560-73.
Cheng Q, Taguchi K, Aleksunes L, Manautou J, Cherrington N, Yamamoto M, Slitt A (2011) Constitutive activation of Nuclear Factor-E2-Related Factor 2 induces biotransformation enzyme and transporter expression in livers of mice with hepatocyte-specific deletion of Kelch-like ECH-associated protein 1. J Biochem Mol Tox. 25:320-9.
Klaassen C, Aleksunes L (2010) Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Invited Review for Pharm. Rev. 62:1-96.
Aleksunes L, Goedken M, Rockwell C, Thomale J, Manautou J, Klaassen C (2010) Transcriptional regulation of renal cytoprotective genes by Nrf2 and its potential use as a therapeutic target to mitigate cisplatin-induced nephrotoxicity. J Pharmacol Exp Ther. 335:2-12.
Aleksunes L, Reisman S, Yeager R, Goedken M, Klaassen C (2010) Nrf2 deletion impairs glucose tolerance and exacerbates hyperglycemia in Type 1 diabetic mice. J Pharmacol Exp Ther. 333:140-51.
Ren H, Aleksunes L, Wood C, Vallant B, George M, Klaassen C, Corton C (2010) Characterization of peroxisome proliferator-activated receptor -independent effects of PPAR- activators in the rodent liver: Di-(2-ethylhexyl) phthalate activates the constitutive activated receptor. Toxicol Sci. 113:45-59.
Awards and Honors
2012, G.O.L.D. Graduate of the Last Decade Award, University of Connecticut Alumni Association
2012, Editorial Boards, Toxicology Letters and Journal of Biochemical and Molecular Toxicology
2011, Outstanding New Environmental Scientist Award, NIH, NIEHS
2011, Society of Toxicology, Membership Committee
2009, Society of Toxicology, Mechanisms Specialty Section, Postdoctoral Award, Baltimore, MD
2008-2012, Pathway to Independence Award K99/R00, NIH, NIDDK
2007, Society of Toxicologic Pathology Travel Award, San Juan, PR
2006, Women in Toxicology Student Achievement Award, San Diego, CA
2005, Lambda Kappa Sigma Young Pharmacist of the Year Award
2004, B. Olive Cole Grant, Lambda Kappa Sigma Professional Pharmacy Fraternity
2004, Rho Chi Pharmacy Honor Society Initiation Speaker
2003-2006, Howard Hughes Predoctoral Fellowship
2002-2003, American Foundation of Pharmaceutical Education-Rho Chi-Schering Plough First Year