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Research Interests:

Dr. Elmquist's laboratory studies the biochemical and physiological determinants of drug absorption, distribution and elimination. Recent studies have focused on the role of drug transport proteins in drug distribution to target tissues. Current research examines the effect that various multidrug resistance proteins (drug efflux pumps), such as the p-glycoprotein (P-gp), and similar efflux proteins, the multidrug-resistance associated proteins (MRPs), have on drug targeting to the central nervous system (CNS). The use of molecular biology, in vitro models, intracerebral microdialysis, and gene knockout animals have been essential tools in this research.

An important project currently underway is the search for strategies to improve the delivery of highly-active anti-retroviral therapy (HAART) to the brain using novel drug delivery systems. Unique animal models of HIV1 encephalitis and transgenic mice deficient in one or more of the genes that encode drug efflux transport proteins are employed to determine both drug distribution and drug efficacy in the CNS. Similar studies are underway to examine the determinants of anticancer drug permeability in the blood-brain barrier. The effective treatment of brain tumor is limited by inadequate delivery of the chemotherapy to the CNS. Some anticancer drugs are substrates for the drug efflux proteins found in these barriers, and therefore an opportunity to improve the targeted bioavailability to the CNS tumor may exist.
Long term objectives of Dr. Elmquist's research include examining expression and regulation of transport systems in key tissues that influence drug disposition, and how variability in expression, either genetically or environmentally controlled, may contribute to variability in drug response in the patient.

Selected Publications:

Shaik N, Giri N, Pan G, Elmquist WF. P-glycoprotein-mediated active efflux of the anti-HIV1 nucleoside abacavir limits cellular accumulation and brain distribution. Drug Metab Dispos. 2007 Nov;35(11):2076-85.

Pan G, Giri N, Elmquist WF. Abcg2/Bcrp1 mediates the polarized transport of antiretroviral nucleosides abacavir and zidovudine.
Drug Metab Dispos. 2007 Jul;35(7):1165-73. Epub 2007

Spitzenberger TJ, Heilman D, Diekmann C, Batrakova EV, Kabanov AV, Gendelman HE, Elmquist WF, Persidsky Y. Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis. J Cereb Blood Flow Metab. 2007 May;27(5):1033-42.

Hitzman CJ, Elmquist WF, Wiedmann TS. Development of a respirable, sustained release microcarrier for 5-fluorouracil II: In vitro and in vivo optimization of lipid coated nanoparticles. J Pharm Sci. 2006 May;95(5):1127-43.

Hitzman CJ, Elmquist WF, Wattenberg LW, Wiedmann TS. Development of a respirable, sustained release microcarrier for 5-fluorouracil I: In vitro assessment of liposomes, microspheres, and lipid coated nanoparticles. J Pharm Sci. 2006 May;95(5):1114-26.

Dai, H. and Elmquist, W.F. Drug transport studies using quantitative microdialysis. Methods in Molecular Biology : The Blood-Brain Barrier: Biology and Research Protocols, S. Nag, editor, 2003.

Sun, H., Dai, H., Shaik, N., and Elmquist, W.F. Drug efflux transporters in the CNS. Advanced Drug Delivery Reviews, 55(1): 83-105, 2003.

Dai, H., Marbach, P., Lemaire, M., Hayes, M., and Elmquist, W.F. Distribution of STI-571 to the brain is limited by p-glycoprotein mediated efflux. J. Pharmacol. Exp. Therap., 304(3):1085-1092, 2003.

Batrakova, E.V., Li, S., Alakhov, V.Ku., Elmquist, W.F., Miller, D.W., and Kabanov, A.V. Sensitzation of cells overexpressing multidrug resistant protein by Pluronic P85. Pharm. Res. 20(10):1581-1590, 2003.