Drug Transporters in ADME
Neuroscience in Denmark
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General informationName (center, department, group or other)
Drug Transporters in ADME
Group Leader, Associate Professor MSK, PhD
26. June 2015
(Last edited: 13. June 2017)
Brief description of research activitiesWe focus on the biology of the blood-brain barrier and drug uptake into the central nervous system. The research group is working with primary cell culture of endothelial cells, astrocytes ans pericytes, as well as genetically engineered cell lines which mimick properties of the brain endothelium. These lab-grown artificial blood brain barriers are used to examine the mechanisms by which drugs can permeate the blood brain barrier. We investigate receptor-mediated transport, transport via small-molecule transport proteins (the SLC superfamily) and efflux via ATP-driven membrane pumps (the ABC superfamily). An important part of our work is also to characterize the interplay between the different cell types in the neurovascular unit, i.e. endothelial cells, astrocytes and pericytes.
Keywordsblood-brain barrier, neurovascular unit, in vitro models, primary culture, brain endothelium, receptor endocytosis, ABC efflux transporters, solute carriers, tight junctions, pericytes
Research tools and techniquesRadioisotope uptake and flux studies
Confocal laser scanning microscopy in combination with immunohistochemistry
Molecular biology techniques, realtime PCR, western blotting, transfections and related techniques.
Flourescense platereader realtime studies of cytsolic calcium and membrane potential
Primary cell culture techniques, mono-cultures, co-cultures, triple-cultures of cells from the neurovascular unit.
Scientific PersonnelNo of Associate Professors/Postdocs: 3
No of PhD students: 3
Key references from within the last 5 yearsHelms HC, Aldana BI, Groth S, Jensen MM, Waagepetersen HS, Nielsen CU, Brodin B (2017). Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model. Journal of Cerebral Blood Flow and Metabolism, 36 (5): 862-890
Siupka P, Hersom M, Lykke-Hartmann K, Johnsen KB, Thomsen LB, Andresen TL, Moos T, Abbott NJ, Brodin B, Nielsen MS (2017): Bidirectional apical–basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells. Journal of Cerebral Blood Flow & Metabolism, Jan 1:271678X17700665. doi: 10.1177/0271678X17700665
Hersom M, Helms HC, Pretzer N, Goldeman C, Jensen AI, Severin G, Nielsen MS, Holm R, Brodin B (2017). Transferrin receptor expression and role in transendothelial transport of transferrin in cultured brain endothelial monolayers. Molecular and Cellular Neuroscience,76:59–67
Helms HC, Abbott NJ, Burek M, Cecchelli R, Couraud PO, Deli MA, Forster C, Galla HJ, Romero IA, Shusta EV, Stebbins MJ, Vandenhaute E, Weksler B, Brodin B. (2016): In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use. Journal of Cerebral Blood Flow & Metabolism, 36(5): 862–890
Saaby L, Helms HC, Brodin B (2016). IPEC-J2 MDR1, a Novel High-Resistance Cell Line with Functional Expression of Human P-glycoprotein (ABCB1) for Drug Screening Studies. Molecular Pharmaceutics 13(2): 640-652
Wolff, A, Antfolk, M, Brodin, B, Tenje, M. (2014) In vitro blood-brain barrier models – an overview of established models and new microfluidic approaches. Journal of Pharmaceutical Sciences. DOI: 10.1002/jps.24329.
Helms, HC, Nielsen, CU, Brodin, B. (2014) Glutamate efflux at the blood-brain barrier: Cellular mechanisms and potential clinical relevance (2014) Archives of Medical Research. 2014 Nov;45(8):639-45
Helms, HC, Hersom, M, Kuhlmann, LB, Badolo L, Nielsen, CU & Brodin, B. (2014) An electrically tight blood-brain barrier model displays net brain-to-blood efflux of substrates for the ABC-transporters, P-gp, BCRP and MRP-1. AAPS J. 16(5):1046-1055