Education:

B.A., Zoology, 1976
University of South Florida

B.S., Pharmacy, 1982
University of Florida

Pharm.D., Clinical Pharmacy, 1984
Ph.D., Pharmaceutics, 1992
University of Minnesota

Research Interests:

Dr. Elmquist's laboratory studies the biochemical and physiological determinants of drug absorption, distribution and elimination. Most of this work has involved the use of in vitro cell culture and in vivo animal models. Recent studies have focused on the role of drug transport proteins in drug disposition. Particular emphasis has been placed on determining the role of membrane-associated drug transport proteins in the distribution of drugs to target tissues. Current research examines the effect that various drug transport systems, such as p-glycoprotein (ABCB1), the multidrug resistance-associated proteins (ABCCx), and the breast cancer resistance protein (ABCG2) have on drug distribution to the central nervous system (CNS). The use of molecular biology, in vitro models, intracerebral microdialysis and gene knockout animals have been important tools in this research.

An important project currently underway is the search for strategies to improve delivery of highly active anti-retroviral therapy (HAART) to the brain using novel drug delivery systems, such as pluronic block copolymers. Unique animal models of HIV1 encephalitis and transgenic mice deficient in one or more of the genes that encode drug efflux transport systems are employed to determine both drug distribution and drug efficacy in limiting the spread of the virus in the CNS. These studies are augmented by mechanistic studies that study the directional flux of solutes across monolayers of cell lines that have been transfected with various transport protein genes, and subsequently stably overexpress these drug efflux proteins.

Similar studies are underway to examine the determinants of anticancer drug permeability in the blood-brain barrier. The effective treatment of many brain tumors is limited by inadequate delivery of the chemotherapy across the barriers of the CNS. Some of these compounds, specifically the molecularly targeted tyrosine kinase inhibitors, may be substrates for the drug efflux proteins found in these barriers and, as such, an opportunity to improve the targeted bioavailability to the CNS tumor may exist by inhibition of the efflux pump.

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:

Kirstein M.N., Brundage R.C., Elmquist W.F., Remmel R.P., Marker P.H., Guire D.E. and Yee D.  Characterization of an in vitro cell culture bioreactor system to evaluate anti-neoplastic drug regimens.  Breast Cancer Res. Treat. 96(3): 217-225 (2006).

Hitzman C.J., Elmquist W.F., Wattenberg L.W. and Wiedmann T.S.  Development of a respirable, sustained release microcarrier for 5-fluorouracil I : In vitro assessment of liposomes, microspheres, and lipid coated nanoparticles.  J. Pharm. Sci. 95(5): 1114-1126 (2006).

Hitzman C.J., Elmquist W.F. and Wiedmann T.J.  Development of a respirable, sustained release microcarrier for 5-fluorouracil II :  In vitro and in vivo optimization of lipid coated nanoparticles.  J. Pharm. Sci. 95(5): 1127-1143 (2006).

Hitzman C.J., Wiedmann T.S., Dai H. and Elmquist W.F.  Measurement of drug release from microcarriers by microdialysis.  J. Pharm. Sci. 94(7): 1456-1466 (2005).

Bachmeier C.J., Spitzenberger T.J., Elmquist W.F. and Miller D.W.  Quantitative Assessment of HIV-1 protease inhibitors interactions with drug efflux transporters in the blood brain barrier.  Pharm. Res. 22(8): 1259-1268 (2005).

Dai H., Chen Y. and Elmquist W.F.  Distribution of the novel antifolate Pemetrexed to the brain.  J. Pharmacol. Exp. Therap. 315(1): 222-229 (2005).

Zhang Y., Schuetz J.D., Elmquist W.F. and Miller D.W.  Plasma membrane localization of multidrug resistance-associated protein (MRP) homologues in brain capillary endothelial cells.  J. Pharmacol. Exp Therap. 311(2): 449-455 (2004). 

Benjamin R.K., Hochberg F.H., Fox E., Bungay P.M., Elmquist W.F., et al.  Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium.  Neuro-Oncology 6(1): 65-74 (2004).

Dai H. and Elmquist W.F.  Drug transport studies using quantitative microdialysis.  Methods Mol. Med. 89: 249-264 (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).

Dash A.K. and Elmquist W.F.  Separation methods that are capable of revealing blood-brain barrier permeability.  J. Chromatography B 797(1-2): 241-254 (2003).