Lester R. Drewes, PhD

University of Minnesota

• Bacaner Award (Minnesota Medical Foundation) Presented to graduate student Zhuo Qian, 1990

External Sources

• CVB Recognition Award, International Conference on CVB, Melbourne, Australia, 2017
• International Brain Barriers Society Award, International CVB Conference, Melbourne, Australia, 2017
• Cerebral Vascular Biology Conference- Outstanding Service Recognition (Montreal), 2013
• Nagai Foundation (Tokyo) Distinguished Lectureship, 2009
• Naito Foundation Award (Japan), 2009
• Alumni Achievement Award, Capital University, 2002
• Jacob Javits Neuroscience Investigator Award (National Institutes of Health), 1998-2006
• Alexander von Humboldt Foundation -- Lynen Postdoctoral Fellowship awarded to Dr. Roman Duelli, Heidelberg, Germany, 1998-1999
• American Diabetes Association-Minnesota Affiliate: 3 Frederick C. Goetz Award, 1993
• Alexander von Humboldt Fellowship Award, 1982-1983
• National Cancer Institute Postdoctoral Fellow, 1971-1972

• Past President, International Brain Barriers Society, 2017
• President, International Brain Barriers Society, 2006-2016
• American Society of Biochemistry and Molecular Biology
• American Physiological Society
• Society for Neuroscience
• International Brain Barriers Society
• American Society for Neurochemistry
• International Society for Cerebral Blood Flow and Metabolism
• International Society for Neurochemistry
• American Association for the Advancement of Science
• Sigma Xi

Committee memberships

• Chair, Society Web Page Committee, Society for Cerebral Blood Flow and Metabolism, 1997-present
• Member, Advisory Committee, Whiteside Research Institute, 1997-present

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.

University of Minnesota Medical School Duluth/UMD

Medical School Courses

• Foundations in Medicine
• Neurological Medicine
• Gastrointestinal Medicine
• Problem-Based Learning (Facilitator)
• Cell and Molecular Biology (member of team faculty)
• Neurosciences/Nervous System (member of team faculty)
• Gastrointestinal Hepatobiliary System
• Medical Biochemistry
• Biochemistry of Specialized Tissues
• Acid-Base Balance (at University of Wisconsin Medical School)

Graduate/Medical School Courses

• Neuroscience (Neurobiochemistry)
• Integrated BioSciences
• Biochemistry
• Biochemistry Laboratory
• Biochemistry Research
• Advanced Biochemistry
• Advanced Biochemical Techniques
• Cell and Molecular Biology
• Toxicology (member of faculty team)
• Clinical Science (Fluids, Electrolytes, and Acid-Base Balance)
• Neurosciences (Guest Lecturer, University of Miami, School of Medicine)

Undergraduate Courses

• Survey of Biochemistry
• Undergraduate Research in Chemistry (Biochemistry)

Mentoring & Advising

• Graduate Students
• Postdoctoral Associates

PROFESSIONAL SERVICE AND PUBLIC OUTREACH

• Associate Editor Board Member, Frontiers 2015-present
• Editor-in-Chief, Fluids and Barriers in the CNS 2013-present
• Honorary Editor, Fluids and Barriers in the CNS 2011-2013
• Member, Editorial Review Board of the Journal of Cerebral Blood Flow and Metabolism, 1989-1996, 2002-present
• Member, Editorial Review Board of the Journal of Neurochemistry 1993-1998
• Member, Editorial Review Board of the Journal of Biological Chemistry 2002-2009

See full list of publications at: PubMed

Publications

Netto JP, Iliff J, Stanimirovic D, Krohn KA, Hamilton B, Varallyay C, Gahramanov S, Daldrup-Link H, d'Esterre C, Zlokovic B, Sair H, Lee Y, Taheri S, Jain R, Panigrahy A, Reich DS, Drewes LR, Castillo M, Neuwelt EA.Neurosurgery. 2017 Jul 21. doi: 10.1093/neuros/nyx357. [Epub ahead of print]

Perez de Lara Rodriguez CE, Drewes LR, Andrews MT.J Comp Physiol B. 2017 Jul;187(5-6):769-778. doi: 10.1007/s00360-017-1076-7. Epub 2017 Mar 21.Keep RF, Jones HC, Drewes LR. Fluids Barriers CNS. 2017 Feb 2;14(1):4. doi: 10.1186/s12987-017-0052-7.

Rodriguez, CEPL*, Drewes, LR, Andrews, MT, Hibernation-based blood loss therapy increases survivability of lethal hemorrhagic shock in rats, J. Comp. Physiol. B. 2017, March DOI 10.1007/s00360-017-1076-7

Keep RF, Jones HC, Drewes LR, Brain barriers and brain fluid research in 2016: advances, challenges and controversies, Fluids Barriers in the CNS. 2017 Feb 2;14(1):4. doi: 10.1186/s12987-017-0052-7

Drewes LR, Jones HC, Keep RF, Advances in brain barriers and brain fluid research and news from Fluids and Barriers of the CNS. Fluids Barriers CNS. 2016 Jan 28;13:1. doi: 10.1186/s12987-016-0026-1

Netto, J.P., Jeffrey Iliff, J., Stanimirovic, D., Krohn, K., Hamilton, B., Varallyay, C., Gahramanov, S., Daldrup-Link, H., d’Esterre, C., Zlokovic, B., Sair, H., Lee, Y., Taheri, S., Jain, R., Panigrahy, A., Reich, D., Drewes, L.R., Neuwelt, E.A., Castillo, M. (2017) Preclinical and Clinical Imaging of the Neurovascular Unit: Permeability, Blood Volume and Functional Imaging (under review)

Liu^, Z., Sneve^, M., Haroldson^, T.A., Smith^, J.P., and Drewes, L.R. (2016) Regulation of monocarboxylic acid transporter 1 trafficking by the canonical Wnt/?-catenin pathway in rat brain endothelial cells, requiring a crosstalk with Notch signaling, J Biol Chem. 291(15):8059-69. doi: 10.1074/jbc.M115.710277

De Feyter, H., Behar, K.L., Rao, J.U., Madden-Hennessey, K., Ip, K.L., Hyder, F., Drewes, L.R., Geschwind, J.-F., de Graaf, R.A., and D. L. Rothman (2016) A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth, Neuro Oncol. 2016 Aug;18(8):1079-87. doi: 10.1093/neuonc/now088

Gurrapu, S., Drewes, L.R. et al (2016) Coumarin carboxylic acids as monocarboxylate transporter 1 inhibitors: In vitro and in vivo studies as potential anticancer agents, Bioorg Med Chem Lett. 2016 Jul 15;26(14):3282-6. doi: 1 0.1016/j.bmcl.2016.05.054

Gurrapu, S., Drewes, L.R. et al (2015) Monocarboxylate Transporter 1 Inhibitors as Potential Anticancer Agents. ACS Med. Chem. Lett., 6(5): 558-561

Liu, Z. and Drewes, L. R. (2014) Monocarboxylic Acid Transporters In: Drug Transporters (G. You and M. M. Morris, eds.), John Wiley and Sons, New Jersey.

Drewes, L. R. Jones HC, Keep RF (2014) News from the editors of Fluids and Barriers of the CNS. Fluids Barriers CNS 11:13

Drewes, L. R. (2014) Frizzled fissure to improve central nervous system drug delivery? J. Cereb. Blood Flow Metab. 34:1157. Journal Impact Factor: 5.339 in 2013; sum of times cited: 0; Role:

Muldoon, L.; Alvarez, J.; ...Drewes, L.R.; Neuwelt, E. (2013) Immunological privilege in the central nervous system and the blood-brain barrier. J. Cereb. Blood Flow Metab. 33:13-21. Journal Impact Factor: 5.339 in 2013; sum of times cited: 40; Role:

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.

Books

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.