Keywords:

Fatty acid binding proteins, sterol carrier protein-2, fatty acid transport proteins (membrane bound), lipid metabolism, arachidonic acid, docosahexaenoic acid, ether lipids, plasmalogens, lipid-mediated signal transduction, brain fatty acid metabolism, heart fatty acid metabolism, animal models, Alzheimer disease, Parkinson disease, Adrenoleukodystrophy, brain phospholipid metabolism, eicosanoids, ApoE, phospholipases, protein purification, knockout animals, analytical lipid techniques.

Education/Training:

• Ph.D., Physiological Chemistry, The Ohio State University
• Assistant Research Scientist, Pharmacology and Physiology, Texas A & M University
• National Research Council Senior Fellow, Laboratory of Neurosciences, National Institute on Aging
  

Research Activity:

How does the brain maintain the unique lipid environment that is essential for normal brain function? This question is the central biological question addressed in my laboratory. This work includes examining the role(s) of specific lipid binding proteins on lipid metabolism in the central nervous system (CNS). For instance, levels of two of fatty acid binding proteins (FABP) found in the CNS will be altered using a variety of techniques including: gene abatement; protein overexpression; and protein expression in cell culture systems. FABP are cytosolic proteins primarily thought to be involved in intracellular lipid metabolism; however work will also focus on intercellular transport, primarily from glia to neurons, and the role of ApoE in this process.

Another important question is, are there specific transport proteins for fatty acids entry into the brain? This process may offer insight into how the brain maintains the unique lipid environment and may involve a number of specific transport proteins that have a role in facilitated transport of fatty acids into the brain. Although the work in my laboratory is focused on CNS, a certain number of these questions can be addressed with regards to fatty acid metabolism in heart and the role of this metabolism in heart lipid-mediated signal transduction. Ultimately, in both the brain and heart, this basic research will be applied to disease processes to gain a better understanding of how lipid metabolism is affected in both health and disease.

I am also interested in elucidating the functional role(s) of plasmalogens in the CNS. Certainly plasmalogens are important lipids found at very high levels in myelin, but are plasmalogens involved in lipid-mediated signal transduction? Do plasmalogens have a major role in neuroinflammatory events? If so, does this role reflect on the lower levels of plasmalogens associated with Alzheimer disease? Preliminary work done in my group at the NIH suggests that plasmalogens are rapidly turned over in the CNS and that this turnover is reflective of a very dynamic process such as lipid-mediated signal transduction. Hence, in keeping with the central question proposed above, this work will continue in my laboratory here at the University of North Dakota.

Books Edited:

1. Lipid-mediated Signaling: Methods in Signal Transduction (2007) ed. E.J. Murphy and
   T.A. Rosenberger, CRC Press, Taylor and Francis Group, Boca Raton, FL, In Press.

Representative Publications:

• Murphy, E.J., Stiles, T. and Schroeder, F. (2000) Sterol carrier protein-2 expression alters phospholipid content and fatty acyl composition in L-cell fibroblasts. J. Lipid Res. 41:788-796.
• Murphy, E.J., Schapiro, M.B., Rapoport, S.I., and Shetty, H.U. (2000) Brain phospholipid composition and levels are altered in Down syndrome brain. Brain Res. 867:9-18
• Murphy, E.J., Zhang, H., Sorbi, S., Rapoport, S.I., and Gibson, G.E. (2000) Phospholipid composition and levels are not altered in fibroblasts bearing presenilin-1 mutations. Brain Res. Bull. 52:207-212.
• Starodub, O., Jolly, C.A., Atshaves, B.P., Roths, J.B., Murphy, E.J., Kier, A.B., and Schroeder, F. (2000) Sterol carrier protein-2 immunolocalization in endoplasmic reticulum and stimulation of phospholipid formation. Am. J. Phys. 279:C1259-C1269.
• Murphy, E.J., Prows, D., Stiles, T., and Schroeder, F. (2000) Phospholipid and phospholipid fatty acid composition of L-cell fibroblast: Effect of intestinal and liver fatty acid binding proteins. Lipids 35:729-738.
• Yarger, D., Patrick, C.B., Rapoport, S.I., and Murphy, E.J. (2000) A continuous fluorometric assay for phospholipase A2 activity in mouse brain cytosol. J. Neurosci. Meth. 100:127-133.
• Patrick, C.B., Krzywkowski, P. Ramassamy, C., Poirier, J., Rapoport, S.I., and Murphy, E.J. (2000) Phospholipase A2 activity is decreased selectively in the hippocampus of aged apolipoprotein E deficient mice. Neurosci. Lett. 288:211-214.
• Murphy, E.J., Rosenberger, T.A., Patrick, C.B., and Rapoport, S.I. (2000) Intravenously injected [1-14C]arachidonic acid targets phospholipids, and [1-14C]palmitic acid targets neutral lipids in hearts of awake rats. Lipids 35:891-898.
• Slivka, A.P. and Murphy, E.J. (2001) High dose methyprednisolone treatment in experimental focal ischemia. Expt. Neurol. 167:166-172.
• DasGupta, S.F., Rapoport, S.I., Gerschenson, M., Murphy, E.J., Fiskum, G. Russell, S.J., and Chandrasekaran, K. (2001) ATP synthesis is coupled to rat liver mitochondrial RNA synthesis Mol. Cell Biochem. 221:3-10.
• Rosenberger, T.A., Oki, J., Purdon, A.D., Rapoport, S.I., and Murphy, E.J. (2002) Rapid synthesis and turnover of brain microsomal ether phospholipids in the adult rat J. Lipid Res. 43:59-68.
• Murphy, E.J. (2002) Sterol carrier protein-2: Not just for cholesterol anymore Mol. Cell. Biochem. 239:87-93.
• Golovko, M.Y. and Murphy, E.J. (2004) An improved method for tissue long chain acyl- CoA extraction and analysis J. Lipid Res. 45:1777-1782.
• Murphy, E.J., Barceló-Coblijn, G., Binas, B., and Glatz, J.F.C. (2004) Heart fatty acid uptake is decreased in heart fatty acid binding protein gene-ablated mice J. Biol. Chem. 279:34481-34488.
• Collison, L.W., Collison, R.E., Murphy, E.J., and Jolly, C.A. (2005) Dietary n-3 polyunsaturated fatty acids increase T-lymphocyte phospholipid mass and acyl-CoA binding protein expression Lipids 40:81-87.
• Patrick, C.B., Rosenberger, T.A., McHowat, J., Rapoport, S.I., and Murphy, E.J. (2005) Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart Am. J. Phys. 288:2611-2619.
• Murphy, E.J., Owada, Y., Kitanaka, N., Kondo, H., and Glatz, J.F.C. (2005) Brain arachidonic acid incorporation is decreased in heart-fatty acid binding protein geneablated mice Biochemistry 44:6350-6360.
• Golovko, M.Y., Hovda, J., Zong-Jin, C, Craigen, W.J., and Murphy, E.J. (2005) Differential alteration of tissue phospholipid mass in mice lacking glycerol kinase, Lipids 40:287-293.
• Castagnet, P.I., Golovko, M.Y., Barceló-Coblijn, G., Nussbaum, R.L., and Murphy, E.J. (2005) Fatty acid incorporation is decreased in astrocytes cultured from alpha-synuclein gene-ablated mice, J. Neurochemistry 94:839-849.
• Golovko, M.Y., Faergeman, N.J., Cole, N.B., Castagnet, P.I., Nussbaum, R.L., and Murphy, E.J. (2005) a-Synuclein gene-deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of "-synuclein palmitate binding, Biochemistry 44:8251-8259.
• Barceló-Coblijn, G.., Collison, L.W., Jolly, C.A., and Murphy, E.J. (2005) Dietary "- linolenic acid increases brain but not heart and liver docosahexaenoic acid levels Lipids 40:787-798.
• Ellis, C.E., Murphy, E.J., Mitchell, D.C., Golovko, M.Y., Scaglia, F., Barceló-Coblijn, G., and Nussbaum, R.L. (2005) Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking "-synuclein Molecular and Cellular Biology 22:10190-10201.
• Murphy, E.J., Huang, H-M, Cowburn, R.F., Lannfelt, L, and Gibson, G.E. (2006) Phospholipid mass is increased in fibroblasts bearing the Swedish amyloid precursor mutation Brain Res. Bull. 69:79-85.
• Relling, D.P., Esberg, L.B., Fang, C.X., Johnson, W.T., Murphy, E.J., Carlson, E.C., Saari, J.T., and Ren, J. (2006) High fat diet induced-obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis J. Hypertension 24:549-561.
• Maddock, T.D., Bauer, M.L., Koch, K., Anderson, V.L., Maddock, R.J., Barcelo-Coblijn, G., Murphy, E.J., and Lardy, G.P. (2006) Effect of processing flax in beef feedlot rations on performance, carcass characteristics, and trained sensory panel ratings J. Animal Sci. In Press.
• Donarum, E.A., Stephan, D.A., Gupta, M., Switzer, R.C., Pearl, P.L., Snead III, O.C., Jansen, E.E.W., Jakobs, C., Murphy, E.J., and Gibson, K.M. (2006) Expression profiling reveals multiple myelin alterations in murine succinate semialdehyde dehydrogenase deficiency J. Inherited Met. Dis. In Press.
• Golovko, M.Y. and Murphy, E.J. (2006) Uptake and metabolism of plasma derived erucic acid by rat brain J.Lipid Res. In Press.
• Golovko, M.Y., Rosenberger, T.A., Faergeman, N.J., Feddersen, S., Cole, N.B., Pribill, I, Berger, J., Nussbaum, R.L., and Murphy, E.J. Acyl-CoA synthetase activity links wildtype but not mutant á-synuclein to brain arachidonate metabolism Biochemistry In Press.
• Ghribi, O., Golovko, M.Y., Larsen, B., Schrag, M., and Murphy, E.J. Deposition of iron and b-amyloid placques is associated with cortical neuronal damage in rabbits fed with long-term cholesterol enriched diets J. Neurochemistry In Press.