Lester R. Drewes, PhD
251 Medical School Duluth
1035 University Drive
Duluth, MN 55812
Biomedical Sciences, Department of
Brain Barriers Research Center
Integrative Biology and Physiology, Department of (IBP)
PhD, University of Minnesota, 1970
The brain depends upon a supply of blood-borne nutrients to maintain its physiological function. A hallmark characteristic of the brain vasculature is an endothelium with tight occluding junctions at positions of cell-cell contact. This absence of spaces between cells prevents bulk diffusion of plasma components into the surrounding tissue. The net result of this "blood-brain barrier" is that influx and efflux of metabolic substrates and nutrients (including glucose, amino acids, and nucleosides) across the brain vasculature must occur via transport systems located in the luminal and abluminal plasma membranes of the endothelial cell. For example, glucose is the primary substrate for brain metabolism and is transported into cells via specific membrane carriers. Under normal glycemic conditions, GLUT1 and GLUT3 are the known members of the glucose transporter family responsible for carrying glucose from the blood and into the cells of the brain. This includes transport across both the luminal and abluminal sides of the endothelial cell and the plasma membranes of the neuronal and glial cells. Although recent studies have greatly expanded our knowledge about glucose transporters in several tissues, much less is currently known about these integral membrane proteins in the brain or how they are regulated in response to pathophysiological conditions. The long-term goals of my research are to characterize the molecular process by which nutrients are transported through the cells comprising the blood-brain barrier (endothelial cells) and the blood-CSF barrier (epithelial cells of the choroid plexus). These goals include an understanding of the molecular identity of the transporters, the membrane sites where transporters are located, the kinetic characteristics of substrate and inhibitor specificity, and, in the future, the mechanisms regulating trans porter activity and expression. Research describing the molecular events of blood-brain transport may be valuable in understanding neurological dysfunctions associated with stroke, diabetes, neurodegenerative diseases and metabolic encephalopathies. Indeed, it could lead to treatment s for minimizing these dysfunctions or for designing therapeutic strategies.
See also: PubMed
Smith, J.P., Uhernik, A.L., Li, L., Liu, Z., and Drewes, L.R. (2012). Regulation of Mct1 by cAMP-dependent internationalization in rat brain endothelial cells. Brain Res 1480:1-11.
Drewes, L.R. (2012). Making connexons in the neurovascular unit. J Cereb Blood Flow Metab 32(8): 1455-6.
Neuwelt, E., Bauer, B., Fahlke, C., Fricker, G., Iadecola, C., Janigro, D., Leybaert, L., Molnar, Z., O'Donnell, M. E., Povlishock, J. T., Saunders, N. R., Sharp, F., Stanimirovic, D., Watts, R. J., and L.R. Drewes (2011) Engaging Neuroscience to Advance Brain Barriers Translational Research, Nature Reviews Neuroscience13:169-184
Klein, A.H., Wendroth, S., Drewes, L.R. and M.T. Andrews (2010) Hibernation strategies to improve recovery from hemorrhagic shock in rats. Shock, 34:565-572.
Andrews, M.T., Russeth, K.P., Drewes, L.R., and P.-G. Henry (2009) Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal. Am J Physiol Regul Integr Comp Physiol. 296:R383-93
Neuwelt, E., Abbott, N.J., Abrey, L., Banks, W.A., Blakley, B., Davis, T. Engelhardt, B., Grammas, P., Nedergaard, M., Nutt, J., Pardridge, W. Rosenberg, G.A., Smith, Q., and L.R. Drewes (2008) Strategies for Advancing Brain-Barriers Translational Research. Lancet Neurology 7:84-96
Henry, P.-G., Russeth, K.P., Tkac, I., Drewes, L.R., Andrews, M.T., and R. Gruetter (2007) Brain energy metabolism and neurotransmission at near-freezing temperatures: an in vivo 1H MRS study of a hibernating mammal. J. Neurochem. 101:1505-1515.
Westholm, D.E., Stenehjem, D.D., Rumbley, J.N., Drewes, L.R., and G.W. Anderson (2007) Organic anion transporting polypeptide 1c1 thyroxine transport is competitively inhibited by the fenamate class of nonsteroidal anti-inflammatory drugs. Endocrinology. 150:1025-32
Smith, J.P., and Drewes, L.R. (2006) Modulation of monocarboxylic acid transporter-1 kinetic function by the cAMP signaling pathway in rat brain endothelial cells. J. Biol. Chem. 281:2053-2060.
Enerson, B.E. and Drewes, L.R. (2006) The rat blood-brain barrier transcriptome. J. Cereb. Blood Flow Metab. 26:959-973.
Doolittle, N.D., Abrey, L.E., Bleyer, W.A., Brem, S., Davis, T.P., Dore-Duffy, P., Drewes, L.R., Hall, W.A., Hoffman, J.M., Korfel, A., Martuza, R., Muldoon, L.L., Peereboom, D., Peterson, D.R., Rabkin, S.D., Smith, Q., Stevens, G.H.J., and Neuwelt, E.A. (2005) New Frontiers in Translational Research in Neuro-oncology and the Blood-Brain Barrier: Report of the Tenth Annual Blood-Brain Barrier Disruption Consortium Meeting. Clin. Cancer Res. 11:421-428.
Enerson, B.E., and Drewes, L.R. (2003) Molecular features, regulation and function of monocarboxylate transporters: Implications for drug delivery. J. Pharm. Sci. 92:1531-1544.
Régina, A., Morchoisne, S., Borson, N.D., McCall, A.L., Drewes, L.R., and Roux, F. (2001) Factors released by glucose-derived astrocytes enhance glucose transporter expression and activity in rat brain endothelial cells. Biochim. Biophys. Acta. 1540:233-242.
Drewes, L.R., and Betz, A.L. (eds.) (1993) Frontiers in Cerebral Vascular Biology: Transport and Its Regulation, Plenum Press, New York.
Chapters in Books, Editorials, & Reports
Matson, C. and Drewes, L.R. (2003) “Detection of Endothelial Proteins by Western Blotting in Methods in Molecular Biology.” Volume X, in The Blood Brain Barrier: Biology and Research Protocols (S. Nag, ed.), p. 479-487.
Anderson, R., Drewes, L., Ntambi, J., Rapoport, S., Hibbeln, J., Yavin, E., Horrocks, L., Moore, S., Salem, N., Preuss, M., Spector, A., Lagarde, M., Kim, H.Y., and Horrobin, D. (2001) Brain uptake and utilization of fatty acids: Applications to peroxisomal biogenesis disorders (An International Workshop) - Roundtable discussion of Session 3: "The regulation and functions of DHA in neurons and neuronal membranes."J. Mol. Neurosci.16(2-3):279-84. (Editorial)
Drewes, L.R., Gerhart, D.Z., Leino, R.L., and Enerson, B.E. (2001) Expression and Modulation of Blood-brain Monocarboxylate Transporters, in The Blood-brain Barrier (D. Koliber, ed.) Kluwer, Amsterdam. p. 9-17.