Al Merrill, Professor and Smithgall Chair in Molecular Cell Biology
Ph.D., Biochemistry, Molecular and Cell Biology, Cornell University
Office: Parker H. Petit Biotechnology (IBB) 3309
Cell regulation by sphingolipid mediators; lipidomics (metabolomics); roles of cell signaling in pathogenesis, cancer prevention and treatment; biomolecular mass spectrometry; biodiversity
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.
Park H, Haynes CA, Nairn AV, Kulik M, Dalton S, Moremen K, Merrill AH Jr. Transcript profiling and lipidomic analysis of ceramide subspecies in mouse embryonic stem cells and embryoid bodies. J Lipid Res. 2010 Mar;51(3):480-9. Epub 2009 Sep 28.
Pewzner-Jung Y, Park H, Laviad EL, Silva LC, Lahiri S, Stiban J, Erez-Roman R, Brügger B, Sachsenheimer T, Wieland F, Prieto M, Merrill AH Jr, Futerman AH. A critical role for ceramide synthase 2 in liver homeostasis: I. alterations in lipid metabolic pathways. J Biol Chem. 2010 Apr 2;285(14):10902-10. Epub 2010 Jan 28.
Pewzner-Jung Y, Brenner O, Braun S, Laviad EL, Ben-Dor S, Feldmesser E, Horn-Saban S, Amann-Zalcenstein D, Raanan C, Berkutzki T, Erez-Roman R, Ben-David O, Levy M, Holzman D, Park H, Nyska A, Merrill AH Jr, Futerman AH. A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy. J Biol Chem. 2010 Apr 2;285(14):10911-23. Epub 2010 Jan 28.
Yin J, Miyazaki K, Shaner RL, Merrill AH Jr, Kannagi R. Altered sphingolipid metabolism induced by tumor hypoxia - new vistas in glycolipid tumor markers. FEBS Lett. 2010 May 3;584(9):1872-8. Epub 2009 Nov 11. Review.
Coward J, Ambrosini G, Musi E, Truman JP, Haimovitz-Friedman A, Allegood JC, Wang E, Merrill AH Jr, Schwartz GK. Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway. Autophagy. 2009 Feb;5(2):184-93. Epub 2009 Feb 6.
Zitomer NC, Mitchell T, Voss KA, Bondy GS, Pruett ST, Garnier-Amblard EC, Liebeskind LS, Park H, Wang E, Sullards MC, Merrill AH Jr, Riley RT. Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1-deoxysphinganine: a novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals. J Biol Chem. 2009 Feb 20;284(8):4786-95. Epub 2008 Dec 18.
Deevska GM, Rozenova KA, Giltiay NV, Chambers MA, White J, Boyanovsky BB, Wei J, Daugherty A, Smart EJ, Reid MB, Merrill AH Jr, Nikolova-Karakashian M. Acid Sphingomyelinase Deficiency Prevents Diet-induced Hepatic Triacylglycerol Accumulation and Hyperglycemia in Mice. J Biol Chem. 2009 Mar 27;284(13):8359-68. Epub 2008 Dec 11.
Merrill AH Jr, Stokes TH, Momin A, Park H, Portz BJ, Kelly S, Wang E, Sullards MC, Wang MD. Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease. J Lipid Res. 2009 Apr;50 Suppl:S97-102. Epub 2008 Nov 21.
Hagen N, Van Veldhoven PP, Proia RL, Park H, Merrill AH Jr, van Echten-Deckert G. Subcellular origin of sphingosine 1-phosphate is essential for its toxic effect in lyase-deficient neurons. J Biol Chem. 2009 Apr 24;284(17):11346-53. Epub 2009 Feb 27.
Goldfinger M, Laviad EL, Hadar R, Shmuel M, Dagan A, Park H, Merrill AH Jr, Ringel I, Futerman AH, Tirosh B. De novo ceramide synthesis is required for N-linked glycosylation in plasma cells. J Immunol. 2009 Jun 1;182(11):7038-47.