Bjoern Bauer, Ph.D.
Pharmacy Practice and Pharmaceutical Sciences
NIEHS/NIH, 2007, Research Triangle Park, NC
Pharmacy, 1997, University of Heidelberg, Germany
Pharmaceutical Sciences/Pharmacology, 2002, University of Heidelberg, Germany
119 Life Science, Duluth
University of Minnesota
College of Pharmacy, Duluth
Department of Pharmacy Practice and Pharmaceutical Sciences
232 Life Science
1110 Kirby Drive
Duluth, MN 55812-3003
Over 1.5 billion people worldwide suffer from brain disorders, including depression, epilepsy, stroke, brain tumors, neuro-AIDS, and Alzheimer’s disease. Thus, there is a huge demand for effective treatments. However, pharmacotherapy of brain disorders is greatly impaired by the blood-brain barrier. The molecular basis for active barrier function is a group of drug efflux transporters such as P-glycoprotein (P-gp), multidrug resistance proteins (MRPs) and breast cancer resistance protein (BCRP). These efflux transporters limit therapeutic drugs from getting into the brain and are a major obstacle for effective treatment of brain disorders.
One strategy to increase drug levels in the brain for better treatment of brain disorders is to manipulate the regulation of efflux transporters at the blood-brain barrier. However, despite the importance of these transporters for the therapy of brain disorders, little is known about their regulation.
We have addressed this fundamental and clinically relevant problem and have described several mechanisms by which drug efflux transporters are regulated at the blood-brain barrier (see figure). Several of these mechanisms provide potential molecular targets for therapy. We are now interested in translating these mechanisms into clinical applications to improve treatment of brain disorders. Currently, we are working on the following projects:
- Regulation of P-glycoprotein in epilepsy
- P-glycoprotein in Alzheimer’s disease
- Modulation of BCRP to treat brain tumors
- blood-brain barrier
- brain cancer
-Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhänel M, Spruß T, Bernhardt G, Graeff C, Färber L, Gschaidmeier H, Buschauer A, Fricker G. Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo, Journal of Clinical Investigation 110(9):1309-1318, 2002.
-Hartz AMS, Bauer B, Fricker G, Miller DS. Rapid regulation of P-glycoprotein at the blood-brain barrier by endothelin-1, Molecular Pharmacology 66(3):387-394, 2004.
-Bauer B, Hartz AMS, Fricker G, Miller DS. Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier, Molecular Pharmacology 66(3):413-419, 2004.
-Hartz AMS, Bauer B, Fricker G, Miller DS. Rapid modulation of P-glycoprotein-mediated transport at the blood-brain barrier by TNF-α and LPS, Molecular Pharmacology 69(2):462-470, 2006.
-Bauer B, Yang X, Hartz AMS, Olson ER, Zhao R, Kalvass JC, Pollack GM, Miller DS. In vivo activation of human PXR tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation, Molecular Pharmacology 70(4):1212-1219, 2006.
-Bauer B, Hartz AMS, Miller DS. TNF-α and endothelin-1 increase P-glycoprotein expression and transport activity at the blood-brain barrier, Molecular Pharmacology 71(3):667-675, 2007.
-Bauer B, Hartz AMS, Pekcec A, Toellner K, Miller DS, Potschka H. Seizure-induced upregulation of P-glycoprotein at the blood-brain barrier through glutamate and COX-2 signaling, Molecular Pharmacology 73(5):1444-1453, 2008.
-Bauer B, Hartz AMS, Lucking JR, Yang X, Pollack GM, Miller DS. Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GSTπ, at the blood-brain barrier, Journal of Cerebral Blood Flow and Metabolism 28(6):1222-1234, 2008.
-Hartz AMS, Bauer B, Block ML, Hong JS, Miller DS. Diesel exhaust particles induce oxidative stress, pro-inflammatory signaling, and P-glycoprotein upregulation at the blood-brain barrier, FASEB Journal 22:2723-2733, 2008.
-Shukla S, Zaher H, Hartz AMS, Bauer B, Ware JA, Ambudkar SV. Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice, Pharmaceutical Research (ePub ahead of print).
-Bauer B, Hartz AMS, Fricker G, Miller DS. Modulation of P-glycoprotein transport function at the blood-brain barrier, Molecular Biology and Medicine 230:118-127, 2005.
-Hartz AMS, Bauer B, Baehr CH, Miller DS, Fricker G. Drug delivery across the blood-brain barrier, Current Nanoscience 1:203-209, 2005.
-Miller DS, Bauer B, Hartz AMS. Modulation of P-glycoprotein at the blood-brain barrier: opportunities to improve CNS pharmacotherapy, Pharmacological Reviews 60(2):196-209, 2008.