Marnett Research Laboratory

Signal Transduction by Lipid Mediators and Lipid Peroxidation Products

A relatively new area of research in the laboratory is the definition of signal transduction pathways stimulated or interrupted by lipid mediators or lipid peroxidation products. The work on lipid mediators is focused on endocannabinoid oxygenation products of COX-2 and 15-lipoxygenase whereas the work on lipid peroxidation products is focused on malondialdehyde, 4-hydroxynonenal, and structurally related molecules. We are particularly interested in events important in controlling the growth and metastasis of cancer cells such as proliferation, migration, apoptosis and angiogenesis. Each of the projects utilizes a range of the outstanding core facilities available at Vanderbilt (microarray, proteomics, and molecular recognition) and involves stimulating collaborations with colleagues at Vanderbilt and elsewhere.

Recent Leading References:

K.R. Kozak, R..A. Gupta, J.S. Moody, C. Ji, W.E. Boeglin, R.N. DuBois, A.R. Brash, and L.J. Marnett "15-Lipoxygenase Metabolism of 2-Arachidonylglycerol: Generation of a PPARa Agonist," J.Biol.Chem, 277, 23278-23286 (2002).

C. Ji, V. Amarnath, J.A. Pietenpol, and L.J. Marnett "4-Hydroxynonenal Induces Apoptosis via Caspase-3 Activation and Cytochrome c Release," Chem.Res.Toxicol, 14, 1090-1096 (2001).

C. Ji, K.R. Kozak, and L.J. Marnett "IkB Kinase, a Molecular Target for Inhibition by 4-Hydroxy-2-nonenal," J.Biol.Chem, 276, 18223-18228 (2001).

T.O. Daniel, H. Liu, J.D. Morrow, B.C. Crews, and L.J. Marnett "Thromboxane A2 is a Mediator of COX-2-Dependent Endothelial Migration and Angiogenesis," Cancer Res., 59, 4574-4577 (1999).