.
Professor, Department of Biochemistry and Biomedical Sciences,
McMaster University
Hamilton, ON, Canada
A.B. (Johns Hopkins University, Baltimore, MDPh.D. (Columbia University, N.Y) Postdoctoral Fellow (Cornell University, N.Y.)Visiting Scientist: Yale University, CT and Campomar Research Institute1999 Avanti Award in Lipid from the Biophysical Society, given to an investigator known for seminal studies in lipid metabolism, lipid enzymology or membranes.Senior Investigator Award of the Canadian Institutes of Health Research (2003)Fellow of the Biophysical Society (2003)epand@mcmaster.ca
RELATIONSHIP BETWEEN MEMBRANE PROPERTIES AND BIOLOGICAL FUNCTION
Our laboratory is interested in the structure and properties of biological membranes. Many cell processes are intimately linked to membranes. These include most signal transduction phenomena, the entry of viruses into target cells, as well as the action of many drugs and cytotoxic agents. We are involved in several studies elucidating the molecular properties of membranes. These include the mechanism of viral fusion and the function of viral fusion proteins; the distribution of cholesterol in membranes and the role of proteinsin sequestering cholesterol-rich domains; the role of lipids in signal transduction; the mechanism of action of antimicrobial peptides and the phenomenon of membrane lysis by different agents leading to cell death. In all of these areas, there is a focus in understanding the relationship between membrane molecular properties and the essential functions of the cell. RECENT PUBLICATIONS:
RF Epand, H Sarig, A Mor and RM Epand (2009). Cell-wall
interactions and the selective bacteriostatic activity of a miniature oligo-acyl-lysyl.
Biophys J. 97(8):2250-2257.
Lung M, Shulga YV, Ivanova PT, Myers DS, Milne SB, Brown HA, Topham MK,
Epand RM (2009) Diacylglycerol kinase
epsilon is selective
for both acyl chains of phosphatidic acid or diacylglycerol. J. Biol. Chem., in press.
RF
Epand, G Wang, B Berno, RM Epand. 2009. Lipid Segregation Explains
Selective Toxicity of a Series of Fragments Derived from the Human
Cathelicidin LL-37. Antimicrob Agents Chemother 53(9):3705-14.
U Schlattner, M Tokarska-Schlattner, S Ramirez, A Brückner, L Kay, C Polge, RF Epand, RM Lee, ML`Lacombe, and RM Epand. 2009.
Mitochondrial kinases and their molecular interaction with cardiolipin. Biochim. Biophys. Acta, In press.
M.L.
Lacombe, M. Tokarska-Schlattner, R.F. Epand, M. Boissan, R.M. Epand, U.
Schlattner. 2009. Interaction of NDPK-D with cardiolipin-containing membranes:
Structural basis and implications for mitochondrial physiology. Biochimie,
91(6):779-83.
N.
Lev, Y. Fridmann Sirkis, L. Blank, A. Bitler, R.F. Epand, R.M. Epand and Y
Shai. 2009. The conformational stability and membrane interaction of the
full-length ectodomain of HIV-1 gp41: implication for mode of action. Biochemistry,
48(14):3166-75.
R.M.
Epand and R.F. Epand. 2009. Lipid domains in bacterial membranes and the
action of antimicrobial agents.
Biochim Biophys Acta, 1788(1):289-94.
S.A.
Vishwanathan, A. Thomas, R. Brasseur, R.F. Epand, E. Hunter and R.M. Epand.
2008. Large changes in the CRAC
segment
of gp41 of HIV do not destroy fusion activity if the
segment interacts with cholesterol. Biochemistry, 47(45):11869-76.
R.M.
Epand, R.F. Epand and P.B.Savage. 2008. Ceragenins
(cationic steroid compounds), a novel class of antimicrobial agents.
Drug News Perspect.,
21(6):307-11.
R.M.
Epand, S. Rotem, A. Mor and R.F. Epand. 2008. Bacterial membranes as
predictors of antimicrobial potency. J. Am. Chem. Soc., 130(43):14346-52.
R.M. Epand and R. F. Epand. 2008. Lipid domains in bacterial membranes and the action of antimicrobial agents.
B.B.A. Biomembranes, in press.
M. Decaffmeyer, Y.V. Shulga, A.O. Dicu, A. Thomas, R. Truant, M.K. Topham, R. Brasseur and R.M. Epand. 2008.
Determination of the topology of the hydrophobic segment of mammalian dyacylglycerol kinase epsilon in a cell membrane and
its relationship to predictions from modeling. J. Mol. Biol, in press.
S.B. Milne, P.T. Ivanova, M.D. Armstrong, D.S. Myers, J. Lubarda, Y.V. Shulga, M.K. Topham, H.A. Brown and R.M. Epand. 2008.
Dramatic differences in the roles in lipid metabolism of two isoforms of diacylglycerol kinase. Biochemistry.47(36):9372-9379.
D. Maysinger, M. Holmes, X. Han, R.M. Epand, E. Portens, A. Foerster, C. Barlas, D.M. Holzman and J. Diamond. 2008. Ceramide is
responsible for the failure of compensatory nerve sprouting in apolipoprotein E knock-out mice. J. Neuroscience, 28(31):7891-7899.
M.L. Mangoni, R.F. Epand, Y. Rosenfeld, A. Peleg, D. Barra, R.M. Epand and Y. Shai. 2008. Lipopolysaccharide, a key molecule
involved in the synergism between temporins in inhibiting bacterial growth and in endotoxin neutralization. J. Biol. Chem., 283(34):22907-22917.
R.M. Epand. Proteins and cholesterol-rich domains. 2008. B.B.A. Biomembranes, 1778(7-8):1576-1582.
R.F. Epand, B.P. Mowery, S.E. Lee, S.S. Stahl, R.I. Lehrer, S.H. Gellman and R.M. Epand. 2008. Dual mechanism of bacterial lethality
for a cationic sequence-random copolymer that mimics host-defense antimicrobial peptides. J. Mol. Biol., 379(1):38-50.
Xm -Z. Lai, Y. Feng, J. Pollard, J. N. Chin, M. J. Rybak, R. Bucki, R.F. Epand, R.M. Epand and P.B. Savage. 2008. Ceragenins:
Cholic acid-based mimics of antimicrobial peptides. Accounts of Chemical Research, in press.
R.F. Epand, Y.-L. Zhang, T. Mirzabekov, B. Kagan, A. Silberstein, W.L. Hubbell, R.M. Epand, S. Cakraborn, D.S. Dimitrov,
W.F. Anderson and Y. Rozenberg. 2008. Membrane activity of an amphiphilic α-helical membrane proximal cytoplasmic domain of
the MoMulLV envelop glycoprotein. Experimental and Molecular Pathology, 84(1):9-17.
J. Liu, R.F. Epand, D. Durrant, D. Grossman, N. Chi, R.M. Epand and R.M. Lee. 2008. Role of phospholipid scramblase 3 in regulation of
tumor necrosis-a-induced apoptosis. Biochemistry, 47(15):4518-4529.
D. Bach, R.F. Epand, R.M. Epand and E. Wachtel. 2008. Interaction of 7-ketocholesterol with two major components of the inner
leaflet of the plasma membrane: phosphatydilethanolamine and phosphatydilserine. Biochemistry, 47(9):3004-3012.
C.R. Benatti, M.T. Lamy and R.M. Epand. 2008. Cationic amphiphiles and the solubilization of cholesterol crystallites in membrane
bilayers. B.B.A. Biomembranes, 1778(4):844-853.
J. Atkinson, R.F. Epand and R.M. Epand. (2008) Tocopherols and tocotrienols in mnembranes: A critical review. Free Radic. Biol.
Med. 44(5):739-764.
A.I. Greenwood, J. Pan, T.T. Mills, J.F Nagle, R.M. Epand and S. Tristram-Nagle. 2008. CRAC motif peptide of the HIV-1 gp41
protein thins SOPC membranes and interacts with cholesterol. B.B.A. Biomembranes, 1778(4):1120-1130.
S. Vishnavathan, A Thomas, R. Brasseur, R.F.Epand, E. Hunter and R.M. Epand. 2008. Hydrophobic substitutions in the first
residue of the CRAC segment of the gp41 protein of HIV. Biochemistry, 47(1):124-130.
J.E. Shaw, R.F. Epand, J.C. Hsu, G.C. Mo, R.M. Epand and C.M. Yip. (2008) Cationic peptide induced remodeling of model
membranes: Direct Visualization by in situ atomic force microscopy. J. Structural Biol., in press.
R.M.Epand, Y.V. Shulga, H.V. Timmins, A.L. Perri, J.D. Belani, K. Peripanathan, L.B. Johnson-McIntire, S. Bajjalieh, A.O. Dicu,
C.
Elias, S.D. Rychnovsky and M.K. Topham.
2007.Substrate Chirality and Specificity of Diacylglycerol Kinases and the
Multisubstrate Lipid Kinase. Biochemistry 46:49:14235-14231.
B.P. Mowery, S.E. Lee, D.A. Kissounki, R.F. Epand, R.M. Epand, B.Weissblum, S.S. Stahl and S.H. Gellman. 2007.
Mimicry of antimicrobial host-defense peptides by random co-polymers. JACS, 129(50):15474-15476.
R.M. Epand, R.M. 2007. Membrane lipid polymorphism: Relationship to bilayer properties and protein function. Methods Mol. Biol.
400:52-26.
R.M. Epand, and M.K. Topham. 2007. Measurements of mammalian diacylglycerol kinase activity in vitro and in cells.
Mehods Enzymol. 434:293-304.
R.S. Atwal, J. Xia, D. Pinchev, J. Taylor, R.M. Epand and R. Truant. 2007. Huntingtin has a membrane association signal that can
modulate huntingtin aggregation, nuclear entry and toxicity. Hum. Mol. Genet.16:2600-2615
E. Gluhov, Y.V. Shulga, R.F. Epand, A.O. Dicu, M.K. Topham, C.M. Deber and R.M. Epand. 2007. Membrane interactions of
he hydrophobic segment of diacylglycerol kinase epsilon. BBA Biomembranes, 1768:2549-2558.
A.O. Dicu, M.K. Topham, L Ottaway and R.M. Epand. 2007. Role of the hydrophobic segment of diacylglycerol kinase epsilon.
Biochemistry, 46(20):6109-6117.
R.F. Epand, P.B.Savage and R.M. Epand. 2007. Bacterial lipid composition and the antimicrobial afficacy of cationic steroid
compounds (ceragenins). BBA Biomembranes, 1768:2500-2509.
J. Lind, T. Ramo, M.R. Klement, E. Barany-Walije, R.M. Epand, R.F. Epand, L. Maler and A. Wislander. 2007. High cationic charge
and bilayer interface-binding helices in a regulatory glycosyltransferase. Biochemistry, 46(19):5664-5677.
B.Y. Baker, R.F. Epand, R.M. Epand and W.L. Miller. 2007. Cholesterol binding does not predict activity of the steroidogenic acute
regulatory protein, StAR. J. Biol. Chem. 282(14):10223-10232.
Y. He, J. Liu, D. Grossman, D. Durrant, T. Sweatman, L. Lothstein, R.F. Epand, R.M. Epand and R.M. Lee. 2007. Phosphorylation of
mitohondrial phosphoilipid sramblase 3 by protein kinase C-delta induces its activation and facilitates mitochondrial targeting of tBid.
J. Cell Biochem. 101:121-1221.
R.F.
Epand, M. Tokarska-Schlatter, U. Schlattner, T Wallimann and R.M. Epand.
2007. Cardiolipin clusters and membrane domain formation
by mitochondrial proteins. J. Molecular Biology, 365(4):968-980.
R.F. Epand, U. Schlatter, T. Wallimann, M.L. Lacombe and R.M. Epand. 2007. Novel lipid transfer property of two mitochondrial proteins
that bridge the inner and outer membranes. Biophysical Journal, 92(1):235-40.
C.R. Benatti, R.M. Epand and M.T. Lamy. 2007. Low cholesterol solubility in DOTAB liposomes. Chem Phys Lipids 145:37-44.
S.P.Handattu, D.W. Garber, D.C. Horn, D.W.Hughes, B. Berno, A.D. Bain, V.K. Mishra, M.N. Palgunachari, G.Datta, G.M. Anantharamiah
and R.M. Epand. 2007. ApoA1 mimetic peptides with differing ability to inhibit atherosclerosis also exhibit differences in their interaction with
membrane
bilayers. J. Biol. Chem., 282(3):1980-1988.
LINK to:
Societe de Biophysique du Canada