 |
Alfred MerrillProfessor and Smithgall Chair in Molecular Cell Biology Office: IBB 3309 Phone: 404-385-2842 Fax: 404-385-2917 |
B.S., Virginia Polytechni Inst. & State University, 1974 (Biochemistry and Nutrition); Ph.D., Cornell University, 1979 (Biochemistry, Molecular and Cell Biology)
Research Interests
Sphingolipid metabolism and cell regulation; Lipidomics and metabolomics (systems biology); Biomolecular mass spectrometry and imaging; Nutrition and environmental health sciences
Current Research
The ability of cells to receive, interpret, and act upon extracellular signals is critical for the proper growth and function of essentially all organisms. This is conducted largely via protein receptors that recognize the initial signals, which are transmitted to intracellular targets via protein-protein interactions, low-molecular weight mediators, and lipids that function both as sites for organization of the signal transduction pathways and as "second messengers". My laboratory studies a category of lipids (termed sphingolipids) that are important in cell structure, cell-cell communication and signal transduction. The major focus of his research is the lipid backbones of sphingolipids (ceramide, sphingosine, sphigosine 1-phosphate and others) that regulate diverse cell behaviors, including growth and programmed cell death (apoptosis). In addition to characterizing the ways that sphingolipids are made, act, and are turned over, our laboratory explores how disease results from disruption of these pathways by (for examples) food borne mycotoxins, environmental contaminants, venoms, and other agents. Studies of naturally occurring and synthetic analogs of these compounds are leading to new strategies for disease prevention and treatment, particularly for certain forms of cancer.
Recent Publications
Shaner RL, Allegood JC, Park H, Wang E, Kelly S, Haynes CA, Sullards MC, Merrill AH Jr. (2009) Quantitative analysis of sphingolipids for lipidomics using triple quadrupole and quadrupole linear ion trap mass spectrometers. J Lipid Res. 2008 Nov 25. [Epub ahead of print]
Coward J, Ambrosini G, Haimovitz-Friedman A, Truman J-P, Allegood JC, Merrill AH Jr.3 and Schwartz GK (submitted) Safingol (l-threo-sphinganine) Induces Autophagy involving inhibition of PKCε and PI3k (in press) Autophagy
Laviad EL, Albee L, Pankova-Kholmyansky I, Epstein S, Park H, Merrill AH Jr, Futerman AH. (2008) Characterization of Ceramide Synthase 2: TISSUE DISTRIBUTION, SUBSTRATE SPECIFICITY, AND INHIBITION BY SPHINGOSINE 1-PHOSPHATE. J Biol Chem. 283(9):5677-84.
Haynes CA, Allegood JC, Sims K, Wang EW, Sullards MC, Merrill AH Jr. (2008) Quantitation of fatty acyl-coenzyme A molecular species in mammalian cell extracts by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS). J Lipid Res. 49(5):1113-25.
Chen Y, Allegood JC, Liu Y, Wang E, Cox TM, Merrill AH Jr, Sullards MC (2008) Imaging MALDI Mass Spectrometry Using an Oscillating Capillary Nebulizer Matrix Coating System and Its Application to Analysis of Lipids in Brain from a Mouse Model of Tay-Sachs/Sandhoff Disease, Anal Chem. 80(8):2780-2788.
Machesky NJ, Zhang G, Raghavan B, Zimmerman P, Kelly SL, Merrill AH Jr, Waldman WJ, Van Brocklyn JR, Trgovcich J. (2008) Human cytomegalovirus regulates bioactive sphingolipids. J Biol Chem. 2008 Jul 20. [Epub ahead of print]
Wang H, Mauer BJ, Liu Y-Y, Wang E., Allegood JC, Kelly S., Symolon H, Liu Y, Merrill AH Jr, Gouazé-Anderson V, Yu J Y, Giuliano AE and Cabot MC (2008) N-(4-hydroxyphenyl)retinamide increases dihydroceramide and synergizes with dimethylsphongosine to enhance cancer cell killing. Mol. Cancer Ther. 7: 2967-2976.
Urs AN, Dammer E, Kelly S, Wang E, Merrill AH Jr, Sewer MB (2007) Steroidogenic factor-1 is a sphingolipid binding protein ol Cell Endocrinol. 265-266:174-8.
Li D, Urs AN, Allegood J, Leon A, Merrill AH Jr, Sewer MB. (2007) cAMP-Stimulated Interaction Between Steroidogenic Factor-1 and Diacylglycerol Kinase-{theta} Facilitates Induction of CYP17. Mol Cell Biol. 27(19):6669-85.
Wu D, Ren Z, Pae M, Guo W, Cui X, Merrill AH, Meydani SN (2007) Aging Up-Regulates Expression of Inflammatory Mediators in Mouse Adipose Tissue, J. Immunol. 179: 4829–4839.
Dhingra S, Freedenberg M, Quo CF, Merrill AH Jr, Wang MD. (2007) Computational modeling of a metabolic pathway in ceramide de novo synthesis. Conf Proc IEEE Eng Med Biol Soc. 2007:1405-8.
Brimble SN, Sherrer ES, Uhl EW, Wang E, Kelly S, Merrill AH Jr, Robins AJ and Schulz TC (2007) The cell surface glycosphingolipids SSEA-3 and SSEA-4 are not essential for human ES cell pluripotency. Stem Cell 25(1):54-62.
Finnegan CM, Rawat SS, Cho EH, Guiffre DL, Lockett S, Merrill AH Jr, Blumenthal R. (2007) Sphingomyelinase Restricts the Lateral Diffusion of CD4 and Inhibits HIV Fusion. J. Virol. 81(10):5294-304
Lamour NF, Stahelin RV, Wijesinghe DS, Maceyka M, Wang E, Allegood JC, Merrill AH Jr, Cho W, Chalfant CE. (2007) Ceramide kinase uses ceramide provided by ceramide transport protein: localization to organelles of eicosanoid synthesis. J Lipid Res. 2007 Jun;48(6):1293-304.
Morales PR, Dillehay DL, Moody SJ, Pallas DC, Pruett S, Allgood JC, Symolon H, Merrill AH Jr.(2007) Safingol toxicology after oral administration to TRAMP mice: demonstration of safingol uptake and metabolism by N-acylation and N-methylation. Drug Chem Toxicol. 30(3):197-216.
Rao RP, Yuan C, Allegood JC, Rawat SS, Edwards MB, Wang X, Merrill AH Jr, Acharya U, Acharya JK. (2007) Ceramide transfer protein function is essential for normal oxidative stress response and lifespan. Proc Natl Acad Sci U S A. 104(27):11364-9.
Seiferlein M, Humpf HU, Voss KA, Sullards MC, Allegood JC, Wang E, Merrill AH Jr. Hydrolyzed fumonisins HFB(1) and HFB(2 )are acylated in vitro and in vivo by ceramide synthase to form cytotoxic N-acyl-metabolites. Mol Nutr Food Res. 51(9):1120-1130
Torres OA, Palencia E, Lopez de Pratdesaba L, Grajeda R, Fuentes M, Speer MC, Merrill AH Jr, O'Donnell K, Bacon CW, Glenn AE, Riley RT (2007) Estimated fumonisin exposure in Guatemala is greatest in consumers of lowland maize. J Nutr. 137(12):2723-9.