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Professor and Head
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 c arrying 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 expa nded 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.
Chapters in Books, Editorials, and Reports:
Drewes, L.R. (1998) The Biology of Blood-Brain Glucose Transporters, in An Introduction to the Blood-Brain Barrier: Methodology and Biology (W.M. Pardridge, ed.) Cambridge University Press, London, p. 165-173.
Drewes, L.R. (1999) Transport of the Brain Fuels: Glucose and Lactate, in Brain Barrier Systems (O. Paulson, ed.) Munksgaard, Copenhagen, p. 285-295.
Drewes, L.R. (1999) What is the Blood-brain Barrier? A Molecular Perspective, in High Altitude Hypoxia-99 (R. Roach, ed.) Kluwer, Amsterdam. Adv. Exp. Med. Biol. 474:111-122.
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.
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)
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.
Articles in Journals:
Bajmoczi, M., Sneve, M., Eide, D.J., and Drewes, L.R. (1997) TAT1 encodes a low affinity histidine transporter in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 243:205-209.
Gerhart, D.Z., Enerson, B.E., Leino, R.L., and Drewes, L.R. (1999) Distribution of monocarboxylate transporters MCT1 and MCT2 in rat retina. Neuroscience 92:367-375.
Leino, R.L., Gerhart, D.Z., and Drewes, L.R. (1999) Monocarboxylate transporter (MCT1) abundance in brains of suckling and adult rats: A quantitative electron microscopic immunogold study. Dev. Brain Res. 113:47-54.
Neuwelt, E.A., Abbot, N.J., Drewes, L.R., Smith, Q.R., Couraud, P.O., Chiocca, E.A., Audus, K.L., Greig, N.H., and Doolittle, N.D. (1999) Cerebrovascular biology and the various neural barriers: Challenges and future directions. Neurosurgery 44:604-608.
Ishihara, H., Wang, H., Drewes, L.R., and Wollheim, C.B. (2000) Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate/lactate in -cells. J. Clinical Invest. 104:1621-1629.
Duelli, R., Enerson, B.E., Gerhart, D.Z., and Drewes, L.R. (2001) Expression of large amino acid transporter LAT1 in rat brain endothelium. J. Cereb. Blood Flow Metab. 20:1557-1562.
Leino, R.L., Gerhart, D.Z., Duelli, R., Enerson, B.E., and Drewes, L.R. (2001) Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem. Int. 38:519-527.
Froberg, M.K., Gerhart, D.Z., Enerson, B.E., Manivel, C., Guzman-Paz, M., Seacotte, N., and Drewes, L.R. (2001) Expression of monocarboxylate transporters MCT1 and MCT2 in normal and neoplastic human CNS tissues. Neuroreport. 12:761-765.
Drewes, L.R. (2001) Molecular architecture of the brain microvasculature: Perspective on blood-brain transport. J. Mol. Neurosci. 16:7-12.
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.
Enerson, B.E., and Drewes, L.R. (2003) Molecular features, regulation and function of monocarboxylate transporters: Implications for drug delivery. J. Pharmaceutical Sci. 92:1531-1544.
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).
Smith, J.P., and Drewes, L.R. (2005) Modulation of MCT1 kinetic function by cAMP signaling pathway in rat brain endothelial cells. (in press)
Gerhart, D.Z., Froberg, M.K., Enerson, B.E., Duelli, R., and Drewes, L.R. (2005) Monocarboxylate transporter MCT1 is increased in brains of Alzheimer’s patients. (under review)
Enerson, B.E., Sneve, M.G., and Drewes, L.R. (2005) Differential gene expression implicating calcium and GABA homeostasis in the anticonvulsant activity of the ketogenic diet. (under review)
Enerson, B.E., and Drewes, L.R. (2005) A molecular portrait of the blood-brain barrier. (under review)
Papers Read at Professional Meetings (Abstracts)
Vedvik, K.L., and Drewes, L.R. (1998) Identification of a sodium independent nucleoside transporter in rat brain. Experimental Biology '98, San Francisco, CA.
Enerson, B.E., Zhdankina, O., Gerhart, D.Z., and Drewes, L.R. (1998) Monocarboxylate transporter 1 (MCT1) expression in developing rat brain. Experimental Biology '98, San Francisco, CA.
Gerhart, D.Z., Leino, R., and Drewes, L.R. (1998) Monocarboxylate transporters MCT1 and MCT2 in rat retinal cells. Experimental Biology '98, San Francisco, CA.
Drewes, L.R., Gerhart, D.Z., Leino, R.L., and Enerson, B.E. (1998) Monocarboxylate transporters (MCTs) at the blood-ocular barrier. Cerebral Vascular Biology '98, Portland, OR.
Drewes, L.R. (1999) Glucose and monocarboxylic acid transporters and their relation to brain energy metabolism. Society for Neurochemistry, New Orleans, LA.
Enerson, B.E., and Drewes, L.R. (1999) Identification of multiple splice variants of monocarboxylate transporter MCT4. Biochemistry and Molecular Biology '99, San Francisco, CA.
Gerhart, D.Z., Leino, R., Duelli, R., Enerson, B., Froberg, K., and Drewes, L.R. (1999) Brain neurons express the monocarboxylate transporter MCT1 protein. 19th Internat'l Symposium on Cerebral Blood Flow and Metabolism, Copenhagen, Denmark.
Duelli, R., Enerson, B., Gerhart, D.Z., Leino, R., West, E.J., and Drewes, L.R. (1999) Brain neurons express the monocarboxylate transporter MCT1 protein. 19th Internat'l Symposium on Cerebral Blood Flow and Metabolism, Copenhagen, Denmark.
Gerhart, D.Z., Enerson, B.E., Duelli, R., Froberg, M.K., Leino, R.L., and Drewes, L.R. (1999) The monocarboxylate transporter MCT1 is increased in brains of Alzheimer's patients. Society for Neuroscience, Vol. 25, Miami, FL, 1999.
Duelli, R., Enerson, B.E., Gerhart, D.Z., Leino, R.L., Sneve, M.G., and Drewes, L.R. (1999) Regulation of monocarboxylate transporters MCT1-4 during ketogenic diet in rat brain. Society for Neuroscience, Vol. 25, Miami, FL, 1999.
Duelli, R., Enerson, B.E., Gerhart, D.Z. and Drewes, L.R. (2000) Large amino acid transporter LAT1 is expressed at the blood-brain barrier. Society for Neuroscience, Vol. 26, New Orleans, LA.
Duelli, R., Enerson, B.E., Gerhart, D.Z. and Drewes, L.R. (2001) Large amino acid transporter LAT1 is expressed at the blood-brain barrier. 20th Internat'l Symposium on Cerebral Blood Flow and Metabolism, Taipei, Taiwan.
Duelli, R., Canis, M., Maurer, M.H., Drewes, L.R. and Kuschinsky, W. (2001) Correlation between densities of monocarboxylate and glucose transporters in rat brain. 20th Internat'l Symposium on Cerebral Blood Flow and Metabolism, Taipei, Taiwan.
Enerson, B.E., Cormier, R.T., and Drewes, L.R. (2001) Generation of a transgenic mouse overexpressing MCT1 in the brain endothelium. 4th Internat'l Conference Cerebral Vascular Biology Blood-brain Barrier, Cambridge, United Kingdom.
Gerhart, D.Z., Leino, R.L., and Drewes, L.R. (2001) Monocarboxylate transporter MCT1 is increased in cerebral cortical capillaries of rats injected with pentylenetetrazole. 4th Internat'l Conference Cerebral Vascular Biology Blood-brain Barrier, Cambridge, United Kingdom.
Enerson, B.E., and Drewes, L.R. (2001) MCT1 induction by cobalt chloride in cultured brain endothelial cells. 4th Internat'l Conference Cerebral Vascular Biology Blood-brain Barrier, Cambridge, United Kingdom.
Enerson, B.E., Sneve, M., Cormier, R.L. and Drewes, L.R. (2002) Differential gene expression in brains of rats fed a ketogenic diet. Experimental Biology 2002, New Orleans, LA.
Henry, P.-G., Russeth, K.P., Tkac, I., Drewes, L.R., Andrews, M.T., and Gruetter, R. (2003) Neurochemical profile of the hibernating ground squirrel measured by 1H NMR spectroscopy. Joint Meeting of the International Society for Neurochemistry, and Asian-Pacific Society for Neurochemistry, Hong Kong, China.
Enerson, B.E., and Drewes, L.R. (2003) The molecular portrait of the cerebral microvasculature. 5th Internat’l Conference on Cerebral Vascular Biology, Amarillo, TX.
Basak, N., Peterson, D., and Drewes, L.R. (2003) A proteomic analysis of the blood-brain barrier. 5th Internat’l Conference on Cerebral Vascular Biology, Amarillo, TX.
Enerson, B.E., and Drewes, L.R. (2003) A serial analysis of gene expression view of the blood-brain barrier. Joint Meeting of the International Society for Neurochemistry, and Asian-Pacific Society for Neurochemistry, Hong Kong, China.
Basak, N., and Drewes, L.R. (2003) A proteomic analysis of the blood-brain barrier. Third Indo-US Workshop on Mathematical Chemistry: With Applications to Drug discovery, Environmental Toxicology, Chemoinformatics and Bioinformatics, Duluth, MN.
Drewes, L.R. (2003) Regulation of MCTs in Brain. Sixth International Meeting for Brain Energy Metabolism, Beijing, China.
Enerson, B.E., and Drewes, L.R. (2003) The rat blood-brain barrier transcriptome. 21st Internat'l Symposium on Cerebral Blood Flow and Metabolism, Calgary, Canada.
Enerson, B.E., and Drewes, L.R. (2003) Transcript analysis of the blood-brain barrier. Third Indo-US Workshop on Mathematical Chemistry: With Applications to Drug discovery, Environmental Toxicology, Chemoinformatics and Bioinformatics, Duluth, MN.
Drewes, L.R. and Enerson, B.E. (2004) Ischemia-induced modifications in the blood-brain barrier. New Frontiers in Translational Research in Neuro-oncology and the Blood-brain Barrier, Bend, OR.
Drewes, L.R. and Enerson, B.E. (2004) Brain vascular genomics following ischemia. Experimental Biology 2004, Washington, DC.
Drewes, L.R. and Smith, J.P. (2004) Modulation of MCT1 kinetic function by the cAMP signaling pathway in rat brain endothelial cells. 7th Symposium Signal Transduction in the Blood-Brain Barriers, Potsdam, Germany.
Matson, C., Basak, S, and Drewes, L.R. (2005) Prediction of blood: brain penetration of chemicals using computed molecular descriptors. Fourth Indo-U.S. Workshop on Mathematical Chemistry, Pune, Maharashtra, India.