††††††††††††††††††††††† Professor, Department of Biochemistry and Biomedical Sciences,
††††††††††††††††††††††††††††††††††††††††††††††††† McMaster University
††††††††††††††††††††††††††††††††††††††††††††††††††††† Hamilton, ON, Canada
† A.B. (Johns Hopkins University, Baltimore, MD
† Ph.D. (Columbia University, N.Y)
† Postdoctoral Fellow (Cornell University, N.Y.)
† Visiting Scientist: Yale University, CT
††Visiting Scientist: Campomar Research Institute
† Avanti Award in Lipid from the Biophysical Society, given to an investigator
† for seminal studies in lipid metabolism, lipid enzymology or membranes.
† Senior Investigator Award of the Canadian Institutes of Health Research
† Fellow of the Biophysical Society
† Honorary Fellow of the Spanish Biophysical Society
† Fellow of the Biophysical Society of Canada
††††††††††††††† RELATIONSHIP BETWEEN MEMBRANE PROPERTIES AND BIOLOGICAL FUNCTION
Many cell processes are intimately linked to their membranes. These include signal transduction phenomena, as well as the action
of many drugs and cytotoxic agents. We are studying the molecular properties of biological membranes and their relationship to biological
function including the phosphatidylinositol cycle and the mechanisms by which the lipid intermediates of this cycle become enriched in specific
acyl chains. The first step in this cycle is catalyzed by diacylglycerol kinase (DGK). In mammals there are 10 known isoforms of this enzyme,
each having a different function and structure. Several disease processes have a connection with changes in expression of one or more of these
isoforms each of which have specific roles in cells. We are also studying membrane curvature and the role of the acyl transferase enzyme, tafazzin,
in determining the acyl chain composition of cardiolipin. Mutations in tafazzin lead to an inherited disease, Barth syndrome, in which patients suffer
from altered cardiolipin and defective mitochondrial function. The roles of mitochondrial membrane curvature properties in processes connected
to apoptosis is also under investigation.
W. Jennings, S. Doshi, K. DíSousa and RM Epand. 2015. Molecular Properties of diacylglycerol kinase-epsilon in
Relation to function. Chem. Phys. Lipids, S0009-3084(15):30001-30003.
RM Epand, D. Bach and E. Wachtel. 2015. Comment on ďCholesterol solubility limit in lipid membranes probed by
small angle neutron scattering and MD simulationsĒ by S. Garg et al. Soft Matter 2014, 10, 9313. Soft Matter,
K. DíSousa and RM Epand. 2015. The phosphatidylinositol synthase-catalyzed formation of phosphatidylinositol does not
exhibit acyl chain specificity. Biochemistry, 54(5):1151-1153.
RM Epand. 2015. Introduction to membrane lipids. Methods Mol Biol 1232:1-6.
U. Schlattner, M. Tokarska-Schlattner, RM Epand, M Boissan, ML Lacombe, J Klein-Seetharaman, VE Kagan. 2015.
Mitochondrial NM23-H4/NDPK-D: a† bifunctional nanoswitch for bioenergetics and lipid signaling. Naunyn Schniedebergs Arch Pharmacol, 388(2):271-278.
RM Epand, K. DíSouza, B. Berno and M. Schlamme. 2015. Membrane curvature modulation of protein activity determined
by NMR. Biochim. Biophys. Acta, 1848(1 PtB):220-228.
K. DíSousa, YJ Kim, T. Balla amd RM Epand. 2014. Distinct properties of the two isoforms of CDP-diacylglycerol kinase.
G. Wang, B. Mishra, RF Epand and RM Epand. 2014. Cathelicidin LL-37 and its fragments. Biochim. Biophys. Acta,
VE Kagan and RM Epand. 2014. Deciphering the misteries of cardiolipins in mitochondria. Chem. Phys. Lipids, 179:1-2.
K. DíSouza and RM Epand. 2014. Enrichment of phosphatidylinositols with specific acyl chains. Biochim, Biophys. Acta
B. Mishra, RF Epand, RM Epand and G. Wang. 2013. Structural location determines functional roles of the basic amino
†acids of KR-12, the smallest antimicrobial peptide from human cathelicidin LL-37. RSC Advances, 42(3):19560-19571.
YV Shulga, D. Loukov, PT Ivanova, SB Milne, DS Myers, GM Hatch, G. Umeh, D. Jalan, MD Fullerton, GR Steinberg,
MK Topham, HA Brown and RM Epand. 2013. Diacylglycerol kinase delta promotes lipogenesis. Biochemistry
U. Ros, MA Edwards, RF Epand, ME Lanio, S. Schreier, CM Yip, C. Alvarez and RM Epand. 2013. The Sticholysin
family of pore-forming toxins induces the mixing of lipids in membrane domains. Biochim. Biophys. Acta 1828(11):
AC Brown, NV Balashova, RM Epand, RF Epand, A. Bragin, MC Kachlany, MJ Walters, Y Du, K. Boescze-Battaglia
and ET Lally. 2013. Aggregatibacter actinomycetemcomitans leukotoxin utilizes a cholesterol recognition/aminoacid
consensus site for membrane association. J Biol. Chem. 288(32):23607-23621.
K. Goldberg, H. Sarig, F. Zaknoon, RF Epand, RM Epand and A. Mor. 2013. Sensitization of Gram-negative bacteria by
targeting the membrane potential. FASEB J. 27(9):3818-3826.
CC Colpitts, AV Ustinov, RF Epand, RM Epand VA Korshun and LM Schang. 2013. 5-(Perylen)-3-yl)sthynyl-arabino-uridine
(aUY11) an arabino-based rigid amphipathic fusion inhibitor, targets virion envelop lipids to inhibit fusion of influenza virus,
hepatitis C virus and other enveloped viruses.J. Virol. 87(7):3640-3654.
A. Prodeus, B. Berno, MK Topham and RM Epand. 2013. The basis of the substrate specificity of the epsilon isoform
of human diacylglycerol kinase is not a consequence of competing hydrolysis of ATP. Chem. Phys. Lipids, 166:26-30.
U. Schalttner, M. Tokarska-Schlattner, S. Ramirez, YY Tyurina, AA Amoscato, D. Mohammadsanyi, Z. Huang, J. Jiang,
N. Yanamala, A. Seffouh, M. Boissan, RF Epand, RM Epand, J. Klein-Seethamaran, Lacombe ML and VE Kagan. 2013.
Dual function of mitochondrial Nm23-H4 in phosphotransfer and intermembrane lipid transfer: a cardiolipin
dependent-switch. J. Biol. Chem., 288:111-121.
YV Shulga, RA Anderson, MK Topham and RM Epand. 2012. Phosphatidylinositol-4-phosphate 5-kinase isoforms exhibit
acyl-chain selectivity for both substrate and lipid activator. J. Biol. Chem. 287(43):35953-35963.
M. Schlame, D. Acehan, B. Berno, Y. Xu, S. Valvo, M. Ren, DL Stokes and RM Epand. 2012. The physical state of lipid
substrates provides transacylation specificity to tafazzin. Nature Chem. Biol., 8:862-869.
M. Tokarska-Schlattner, RF Epand, F. Meiler, G. Zandomeneghi, D. Neumann, HR Widmer, BH Meier, RM Epand, V. Sacks and
U. Schlattner. 2012. Phosphocreatine interacts with phospholipids, affects membrane properties and exerts membrane-protective effects.
PLoS One, 7(8):e43178.
P. Wadhwani, RF Epand, N. Heidenreich, J. Burck, AS Ulrich and RM Epand. 2012. Membrane-active peptides and the clustering
of anionic lipids. Biophys. J. 103(2):265-274.
F. Zaknoon, K. Goldberg, H. Sarig, RF Epand, RM Epand A. Mor. 2012. Antibacterial properties of an oligo-hexyl-lysyl hexamer
targeting GramĖnegative species. Antimicrob. Agents Chemother. 56(9):4827-4832.
G. Wang, RF Epand, VC Thomas, K. Bayles and RM Epand. 2012. Decoding the functional role of cationic side chains of the major
antimicrobial region of hyman cathelicidin LL-37. Antimicrobial Agents and Chemotherapy, 56(2):845-856.
AC Brown, K. Boesce-Battaglia, Y. Du, FP Stefano, IR Kieba, RF Epand, L Kabalis, PL Yeagle, RM Epand, ET Lally (2012).
Aggregatibacter Actinomicetemcomitans leukotoxin cytotoxicity occurs through bilayer destabilization. Cell Microbiol., 14(6):869-881.
K. DíSouza and RM Epand. 2012. Catalytic activity and acyl-chain selectivity of diacylglycerol kinase-e are modulated by residues in
and near the lipoxygenase-like motif. J. Mol. Biol. 416(5):619-628.
RM Epand. 2012. Recognition of polyunsaturated acyl chains by enzymes acting on membrane lipids. B.B.A. Biomembranes, 1818(4):957-962.
RM Epand. 2012. Further insights into the properties of the HIV-gp41 fusion domain: commentary on the article by AL Lai et al, J.
Mol. Biol.† 418(1-2):1-2.
S. Aoki and RM Epand. 2012. Caviolin-1 hydrophobic segment peptides insertion into membrane mimetic systems. Role of Proline residue.
B.B.A. Biomembranes, 1818(1):12-18.